Is there any evidence it makes people live longer?

What this archive is for. Trials of the compound come first, ranked by how many people were actually given it. Studies that only observed people are below them and labelled.

1. 01Relaxin-2PeptideStrong. At least two finished studies in people, and at least 1,000 people who took it. 2 completed trials, 7,706 people given it.5 reported

   1,161 people given it1 trial, 1 watch-only1 found nothing

   • found nothingSerelaxin eased breathlessness a little in people admitted with sudden heart failure, and changed nothing that matters more. 1,161 people got either a two day drip of the drug or a dummy drip soon after reaching hospital. Breathlessness scored better on one scale and no better on the other. Deaths from heart causes and readmissions at two months were unchanged. A death count at six months leaned the drug's way, but that was a side question, not what the trial was built to prove. Funded by a Novartis company.

     The numbers 1,161 patients hospitalised with acute heart failure randomised 1:1 to a 48 hour infusion of serelaxin at 30 micrograms per kilogram per day or placebo within 16 hours of presentation. Serelaxin improved the visual analogue scale dyspnoea endpoint by 448 mm times hours (95 percent CI 120 to 775, p = 0.007) but had no effect on the co-primary Likert endpoint (27 percent against 26 percent, p = 0.70). There was no effect on cardiovascular death or readmission at 60 days (hazard ratio 1.02, 0.74 to 1.41) or on days alive out of hospital. Among prespecified additional endpoints, 42 deaths occurred by day 180 on serelaxin against 65 on placebo, hazard ratio 0.63 (0.42 to 0.93, p = 0.019). Funded by Corthera, a Novartis affiliate company. Registered as NCT00520806.

     The Lancet, 2013· 1,161 people

   • Investigators went back through every death in the failed trial to work out why the earlier trial had looked promising, and found nothing to rescue it. By six months about one patient in nine had died, and heart failure caused nearly four in ten of those deaths. The drug changed no category of death. People aged 75 and over died more often, and more often of something other than their heart. This explains the failure. It does not undo it.

     The numbers An adjudicated analysis of every death in RELAX-AHF-2, run specifically to understand why the two trials disagreed. By 180 days 11.5 percent of patients had died, 38 percent of those deaths from heart failure. Unlike in RELAX-AHF, there was no apparent effect of serelaxin on any category of cause of death. Patients aged 75 or over died more often (14.2 percent against 8.8 percent) and more often from non-cardiovascular causes. Patients with preserved ejection fraction had less heart failure mortality (30 percent against 40 percent) and more non-cardiovascular mortality (36 percent against 20 percent).

     JACC: Heart Failure, 2020· number of people not givenobserved only, nobody was given it

2. 02Thymalin with epitalonBlendStrong. At least two finished studies in people, and at least 1,000 people who took it. 2 completed trials, 1,106 people given it.7 reported

   1,106 people given it2 trials1 found nothing

   • found nothingA defined thymus peptide was put through a modern study, and it failed. Just over a thousand people seriously ill with sepsis got either thymosin alpha-1 or a dummy shot, and nobody involved knew which. A month later, the same share had died in each group. It is on this page as a contrast. When a thymus peptide is finally tested at full size under modern rules, the answer can come back empty, and this one did.

     The numbers 1,106 adults with sepsis, 22 centres, double blinded and placebo controlled. 28 day all cause mortality was 23.4% on thymosin alpha-1 and 24.1% on placebo, hazard ratio 0.99, p = 0.93. Included here as the contrast: this is what a defined thymic peptide looks like when tested under modern conditions, and the result was null.

     BMJ, 2025· 1,106 people

   • This is the study the thymalin story rests on, and it is not built to carry that weight. 266 older people were followed for six to eight years, and given thymalin and epithalamin in the first two or three. Infections and deaths were reported at about half the rate of a comparison group, and several age-related diseases as less common. The problem is this. The paper does not say anyone was grouped by chance or kept unaware of their treatment. And no other team has repeated it.

     The numbers 266 elderly and older persons assessed over six to eight years, with thymalin and epithalamin applied during the first two to three years. Acute respiratory disease incidence fell 2.0 to 2.4-fold, with reduced clinical ischaemic heart disease, hypertension, deforming osteoarthrosis and osteoporosis against control. Mortality fell 2.0 to 2.1-fold with thymalin, 1.6 to 1.8-fold with epithalamin and 2.5-fold with both, and a separate group treated with both annually for six years had a 4.1-fold lower mortality rate. Single group, no described blinding or randomisation, never replicated.

     Neuro Endocrinology Letters, 2003· number of people not given

3. 03Thymosin Alpha-1PeptideStrong. At least two finished studies in people, and at least 1,000 people who took it. 2 completed trials, 1,204 people given it.7 reported

   1,106 people given it1 trial, 1 watch-only1 found nothing

   • The biggest test thymosin alpha-1 has ever been put through, and it failed. 1,106 adults who were seriously ill with sepsis got either the peptide or a dummy injection, across 22 hospitals in China. A month later, 23.4% of the treated group had died of any cause, against 24.1% on the dummy. That gap is smaller than one person in a hundred. A trial this large would have found a real benefit if there was one to find.

     The numbers 1,106 adults with sepsis at 22 Chinese centres: 28-day mortality 23.4% with thymosin alpha-1 vs 24.1% with placebo (HR 0.99), so no clear mortality benefit.

     BMJ, 2025· 1,106 people

   • found nothingAn earlier, smaller sepsis trial leaned towards a benefit that a bigger trial later failed to confirm. 361 patients at six Chinese hospitals were split by chance into a thymosin alpha-1 group and a comparison group. The patients did not know which they were in. Their doctors did. After 28 days, 26.0% of the treated patients had died of any cause against 35.0% of the others. That gap was not big enough to separate from chance. The larger TESTS trial later found no difference.

     The numbers 361 patients at six Chinese centres: 28-day all-cause mortality 26.0% versus 35.0%, relative risk 0.74 (95% CI 0.54 to 1.02), P=0.062 unstratified. Single-blind. The larger double-blind TESTS trial later found no difference.

     Critical Care, 2013· 361 peopleobserved only, nobody was given it

4. 04Thymosin alpha-1 with KPV and LL-37BlendStrong. At least two finished studies in people, and at least 1,000 people who took it. 3 completed trials, 1,140 people given it.6 reported

   1,106 people given it1 trial

   • This was the biggest test thymosin alpha-1 has been through, and it failed. Just over a thousand people seriously ill with sepsis got either the peptide or a dummy shot for a week. Nobody involved knew which. A month later, the same share had died in each group. Nothing else measured came out different. A study this size would have found a benefit if there was one. Some authors were paid by the maker, and they said so.

     The numbers 1,106 adults with sepsis across 22 centres in China, randomised 1 to 1 to subcutaneous thymosin alpha-1 or placebo every 12 hours for seven days. 28 day all cause mortality was 23.4% on thymosin alpha-1 and 24.1% on placebo, hazard ratio 0.99, 95% CI 0.77 to 1.27, p = 0.93. No secondary or safety outcome differed significantly. The trial found no clear evidence that thymosin alpha-1 decreases 28 day mortality in sepsis. Several authors received grants from the manufacturer, disclosed in the paper.

     BMJ, 2025· 1,106 people

5. 05VasopressinPeptideModerate. At least one finished study in people, and at least 100 people who took it. 1 completed trial, 778 people given it.3 reported

   778 people given it1 trial

   • Swapping one blood pressure drug for another did not save more lives. Seven hundred and seventy eight people in septic shock were given low dose vasopressin or the standard drug, norepinephrine. By 28 days, 35.4 percent of the vasopressin group had died and 39.3 percent of the standard group had. That gap is small enough that chance explains it. A trial this size would have picked up a real difference. Vasopressin is a reasonable alternative here, not an improvement.

     The numbers 778 patients: 28-day mortality 35.4% with low-dose vasopressin versus 39.3% with norepinephrine, not significantly different.

     New England Journal of Medicine, 2008· 778 people

6. 06TirzepatidePeptideStrong. At least two finished studies in people, and at least 1,000 people who took it. 9 completed trials, 22,802 people given it.11 reported

   731 people given it1 trial

   • Tirzepatide cut heart failure flare-ups in people with a stiff heart and obesity. 731 patients were followed for about two years on the drug or a dummy shot. Death from heart causes or worsening heart failure hit 9.9% on the drug and 15.3% on the dummy, about 54 fewer such events for every 1,000 people. Almost all of that came from fewer heart failure events. Deaths from heart causes alone ran slightly higher on the drug, 2.2% against 1.4%, on numbers too small to read either way.

     The numbers SUMMIT, 731 patients over a median 104 weeks: cardiovascular death or worsening heart failure in 9.9% versus 15.3% (HR 0.62). Cardiovascular deaths alone were 2.2% versus 1.4% (HR 1.58, 95% CI 0.52 to 4.83), so the composite was driven by heart-failure events.

     New England Journal of Medicine, 2025· 731 peoplepoints the wrong way

7. 07TriptorelinPeptideStrong. At least two finished studies in people, and at least 1,000 people who took it. 4 completed trials, 1,388 people given it.5 reported

   424 people given it1 trial

   • This trial is about when to give radiotherapy, not about triptorelin, and it found no advantage in giving it early. Triptorelin was the hormone treatment handed to both groups, so it was never the thing being tested. 424 men who had had prostate surgery were assigned to immediate radiotherapy or to waiting until their cancer marker rose. Six years on, about the same share in each group were free of events. The men treated immediately had far more urinary problems and erectile trouble. Read the assignment before reading the result.

     The numbers 424 men randomised after radical prostatectomy to adjuvant radiotherapy or to early salvage radiotherapy on biochemical relapse, with triptorelin given as background androgen deprivation to both arms. 5 year event free survival was 92 percent against 90 percent (HR 0.81, 95% CI 0.48 to 1.36, log-rank p=0.42), so no advantage to treating immediately, while late grade 2 or worse genitourinary toxicity ran 59 percent against 22 percent. Enrolment was stopped early for unexpectedly low event rates. Triptorelin was never the variable under test, which is why this trial is frequently and wrongly listed as triptorelin evidence: it reports on radiotherapy timing.

     The Lancet Oncology, 2020· 424 people

8. 08IO102-IO103PeptideModerate. At least one finished study in people, and at least 100 people who took it. 3 completed trials, 470 people given it.3 reported

   407 people given it1 trial

   • The vaccine looked like it was helping, and the trial still counts as a failure. Four hundred and seven people with advanced melanoma got a standard immune drug, half of them with the vaccine added, and everyone knew which. Cancer took much longer to worsen in the vaccine group, close to nineteen months against eleven. The gap fell just short of the bar the trial had set in advance, so the result does not stand. More than half had a reaction where the shot went in. The maker paid.

     The numbers Open label phase 3, 407 patients with untreated advanced melanoma randomised 1:1 to IO102-IO103 (85 mcg each) plus pembrolizumab or pembrolizumab alone for up to 2 years. Median progression free survival 19.4 versus 11.0 months, HR 0.77 (95% CI 0.58 to 1.00), p = 0.0558; the prespecified threshold of p at most 0.045 was missed. Grade 3 or worse treatment related adverse events 14.5 versus 15.6 percent; injection site reactions in 56 percent. Sponsored by IO Biotech; the authors declare extensive industry relationships.

     Annals of Oncology, 2026· 407 people

9. 09ThymalinPeptideModerate. At least one finished study in people, and at least 100 people who took it. 4 completed trials, 308 people given it.7 reported

   308 people given it3 trials

   • This is the study the thymalin story rests on, and it is not built to carry it. 266 older people in Russia and Ukraine were followed for six to eight years, dosed only in the first two or three. In the thymalin group, chest and airway infections were reported at roughly half the usual rate, and deaths at about half as well. Adding the pineal peptide was reported to lower deaths further still. Everybody knew who got what, and every figure comes from one research group.

     The numbers 266 elderly people in Russia and Ukraine followed 6 to 8 years, treated during the first 2 to 3 years: in the Thymalin arm acute respiratory illness fell 2.0 to 2.4-fold and mortality was 2.0 to 2.1-fold lower than control; combined with Epithalamin the reported reduction was 2.5-fold, and 4.1-fold in a subgroup dosed annually for 6 years. Open-label, single research lineage.

     Neuro Endocrinology Letters, 2003· 266 people

   • A small early-pandemic trial reported faster recovery, and nobody died in either group. 42 patients got thymalin injections into the muscle for five days on top of standard care, and 50 got standard care alone, at one hospital in mid 2020. Lung scans worsened in 2 of the 42 treated against 5 of the 50 controls. Markers of inflammation fell faster on the drug. Everybody knew who was getting it. With no deaths at all, the trial cannot say whether thymalin saves lives.

     The numbers Single-centre, open-label, prospective randomized controlled trial, April to July 2020: 42 patients received thymalin 10 mg intramuscularly daily for 5 days plus standard care, 50 received standard care. No deaths in either group. Radiological progression in 2 of 42 treated against 5 of 50 controls, with faster falls in IL-6, C-reactive protein and D-dimer.

     Stem Cell Reviews and Reports, 2021· 42 people

   • The reported death rates favour thymalin, and the paper contradicts itself. Severely ill COVID patients were split three ways: standard care, tocilizumab, or thymalin. The English abstract puts hospital deaths at 40.9% on standard care, 28.4% with tocilizumab and 20.6% with thymalin. The Russian abstract of the same paper gives different figures for two of those groups. Group sizes are never reported anywhere. A death rate with no group size behind it, in a paper that disagrees with itself, cannot be relied on.

     The numbers Three-arm comparison in severe COVID-19 in middle-aged and elderly patients: hospital mortality 40.9% on standard therapy, 28.4% with tocilizumab and 20.6% with thymalin, per the English abstract. Group sizes are not reported, and the paper's own Russian abstract gives different figures for two arms (28.8% and 16.2%).

     Advances in Gerontology, 2022· number of people not given

10. 10RetatrutidePeptideStrong. At least two finished studies in people, and at least 1,000 people who took it. 5 completed trials, 1,345 people given it.8 reported

    281 people given it1 trial

    • Retatrutide lowered blood sugar and weight more than an older drug, in a mid-stage trial. 281 people with type 2 diabetes were split by chance between retatrutide, dulaglutide and a dummy shot, and nobody involved knew which. At the top dose, average blood sugar over three months fell about 2 points, against almost nothing on the dummy and 1.41 on dulaglutide. Weight fell 16.94% against 3.00%. Nobody had a severe sugar low and nobody died. It ran under a year.

      The numbers 281 randomized, 275 analysed (NCT04867785): HbA1c -2.02% at 12 mg versus -0.01% on placebo and -1.41% on dulaglutide at 24 weeks; body weight -16.94% versus -3.00% and -2.02% at 36 weeks. No severe hypoglycaemia and no deaths.

      The Lancet, 2023· 281 people

11. 11EpitalonPeptideModerate. At least one finished study in people, and at least 100 people who took it. 5 completed trials, 266 people given it.6 reported

    266 people given it3 trials

    • This is the study the life extension claim rests on, and it is not built to carry it. 266 older people in Russia and Ukraine were followed for six to eight years, dosed only in the first two or three. Deaths were reported lower in every treated group, from about a third fewer up to four times fewer in one small subgroup dosed every year. Chest and airway infections were reported at roughly half the usual rate. Everybody knew who got what, and every figure comes from one group.

      The numbers 266 elderly people in Russia and Ukraine followed 6 to 8 years, treated during the first 2 to 3 years: mortality 1.6 to 1.8-fold lower with Epithalamin, 2.0 to 2.1-fold lower with Thymalin, 2.5-fold lower with both, and 4.1-fold lower in a subgroup given both annually for 6 years; acute respiratory illness fell 2.0 to 2.4-fold. Open-label, single research lineage.

      Neuro Endocrinology Letters, 2003· 266 people

    • A long Russian study reported fewer deaths, and nobody was kept in the dark. Older heart patients showing signs of fast ageing were followed for twelve years. Some got courses of epithalamine on top of usual treatment, the rest had usual treatment only. Deaths from any cause were reported 28% lower, and deaths from heart disease half as common. They scored younger on a measure of functional age and could exercise for longer. There was no dummy treatment, so belief and extra attention cannot be ruled out.

      The numbers 12-year randomized study in elderly coronary patients with accelerated cardiovascular aging: total deaths 28% lower and cardiovascular mortality 2-fold lower than control on the same basic therapy, with lower functional age and higher exercise tolerance. Not blinded, not placebo-controlled.

      Bulletin of Experimental Biology and Medicine, 2006· number of people not given

    • The same small group of Kiev heart patients, followed for much longer. 39 heart patients took six courses of epithalamin over three years alongside their usual treatment. 40 others had usual treatment only. The treated group was reported to age more slowly in the heart and blood vessels, keep more stamina, recover a normal melatonin rhythm and die less often. Seventy-nine people is a very small base for a claim about dying. The title says pituitary gland; the preparation studied is the pineal one.

      The numbers The same Kiev cohort at 15 years: 39 coronary patients given 6 courses of Epithalamin over 3 years plus basic therapy versus 40 on basic therapy alone, reporting slower cardiovascular aging, preserved physical endurance, normalized melatonin rhythm and significantly lower mortality. The title says pituitary; the text is about the pineal preparation Epithalamin.

      Bulletin of Experimental Biology and Medicine, 2011· number of people not given

12. 12Angiotensin-(1-7)PeptideLimited. People have taken it in a published study, but fewer than 100 of them. 5 completed trials, 76 people given it.3 reported

    20 people given it1 trial

    • Given alone to people with an advanced cancer, it did not change the course of the disease. 20 people with sarcoma that had spread got a daily shot under the skin. Their cancer held off for about 2.7 months on average and they lived about 10.2 months. Two people with blood vessel tumours stayed stable far longer. A blood marker effect seen in the first study did not show up again. Everybody got the drug, so there is nothing to compare these figures against.

      The numbers 20 people with metastatic sarcoma received 20 mg subcutaneously daily. Median progression-free survival 2.7 months (95 percent confidence interval 1.4 to 4.1) and median overall survival 10.2 months (5.3 to 18.3). The placental growth factor biomarker effect seen in phase 1 was not confirmed. Two people with vascular sarcomas had prolonged disease stabilisation at 10 and 19 months.

      Sarcoma, 2016· 20 people

13. 13ANPPeptideModerate. At least one finished study in people, and at least 100 people who took it. 4 completed trials, 188 people given it.4 reported

    4 people given it1 trial, 2 watch-only1 found nothing

    • This one points the other way, and the page keeps both. Two Japanese groups of patients were pooled, 2,435 in all, and sorted by how much carperitide they had been given. Over the following year, deaths from heart causes and from any cause were lower in the low-dose group than in those given none or almost none. This is watching what doctors already did. It cannot tell you what the drug caused.

      The numbers Pooled analysis of two Japanese cohorts, 2,435 patients with acute decompensated heart failure split by carperitide dose. Cardiovascular and all-cause mortality within 1 year were lower in the low-dose group (at or above 0.02 micrograms per kilogram per minute) than in the no-carperitide and very-low-dose groups. This observational result points in the opposite direction to the propensity-matched in-hospital analyses and is reported here alongside them, not instead of them.

      ESC Heart Failure, 2022· 2,435 peopleobserved only, nobody was given it

    • found nothingPooled across every study they could find, people given this drug were more likely to die in hospital. The researchers gathered 9 studies. 4 were planned trials and 5 compared matched patients from hospital records. The studies disagree with each other a lot, which weakens the pooled answer. The 4 planned trials alone were far too small to say anything either way. Long-term deaths, return trips to hospital, low blood pressure and length of stay were all similar. This is a warning sign, not a settled harm.

      The numbers 9 studies, 4 randomised and 5 propensity score-matched. Pooled in-hospital mortality was higher with carperitide, odds ratio 1.38, 95 percent confidence interval 1.07 to 1.78, with high heterogeneity (I squared 77 percent). The 4 randomised trials alone gave odds ratio 0.85 with a 95 percent confidence interval of 0.07 to 10.49, which is uninformative. No significant difference in long-term mortality, rehospitalisation, hypotension or length of stay.

      BMC Cardiovascular Disorders, 2025· 4 people

    • In Japanese hospital records, patients given this drug died more often than closely matched patients who were not. Researchers looked back at 402 treated patients and paired 367 of them with similar untreated ones. Death in hospital was about twice as likely in the treated group, and the gap was wider in older patients. Doctors chose who got this drug, and sicker patients are more likely to be chosen. So treatment and how sick people were cannot be pulled apart here.

      The numbers Retrospective multicentre cohort, 402 of the patients treated with carperitide, 367 matched pairs analysed. Carperitide was associated with in-hospital mortality, odds ratio 2.13, 95 percent confidence interval 1.17 to 3.85, with a larger association in older patients (odds ratio 2.93, 1.54 to 5.91). Observational, so treatment choice and severity cannot be separated.

      Journal of Cardiac Failure, 2015· number of people not givenobserved only, nobody was given it

14. 14LanreotidePeptideLimited. People have taken it in a published study, but fewer than 100 of them. 1 completed trial, none stating how many people.4 reported

    0 people given it1 trial

    • Lanreotide slowed these tumours down, and that is a rare thing for a peptide to prove. 204 adults with advanced neuroendocrine tumours were split by chance. Half had a lanreotide shot every 28 days for up to two years. Half had a dummy shot, and nobody involved knew which. At two years, 65% of the lanreotide group were still free of tumour growth, against 33% on the dummy shot. People did not live longer and did not feel better. Ipsen, which sells the drug, paid for the trial.

      The numbers The CLARINET randomised phase 3 in metastatic enteropancreatic neuroendocrine tumours, showing prolonged progression-free survival on lanreotide. A hard clinical endpoint in a randomised trial, which very few peptides documented on this site can claim.

      New England Journal of Medicine, 2014· number of people not given

15. 15IcatibantPeptideModerate. At least one finished study in people, and at least 100 people who took it. 5 completed trials, 306 people given it.4 reported

    0 people given it1 trial1 found nothing

    • found nothingThe main thing this study set out to show, it did not show. 73 people in hospital with COVID-19 pneumonia got icatibant on top of usual care, or usual care alone. Recovery by day 10 was better on the drug, but not by enough to count. By 28 days, everyone on icatibant had recovered against about 83 in every hundred on usual care. 6 people on usual care died, against none on the drug. Everybody knew who was getting what.

      The numbers 73 inpatients with COVID-19 pneumonia randomised to icatibant plus standard care or standard care alone. The primary endpoint, clinical response at day 10 or discharge, was 73.0 versus 55.6 percent and did not reach significance (p = 0.115). The secondary endpoint at 28 days favoured icatibant (100 versus 83.3 percent, p = 0.011) and no deaths occurred on icatibant versus 6 on control. Open-label and small, with the primary endpoint missed.

      Clinical Infectious Diseases, 2023· number of people not given

16. 16MecaserminPeptideLimited. People have taken it in a published study, but fewer than 100 of them. 1 completed trial, 76 people given it.6 reported

    nobody was given it1 watch-only study

    • Men with naturally higher IGF-1 in their blood get prostate cancer somewhat more often. Nearly 200,000 men were followed for about seven years. 5,402 were diagnosed with prostate cancer and 295 died of it. The higher a man's level, the higher his risk, and a genetic analysis pointed the same way, which makes a real cause more likely. Nobody was given anything here. These were men with their own natural levels, not patients on mecasermin, and this does not show that treating a deficient child raises his cancer risk.

      The numbers The epidemiology that any page about giving people more IGF-1 has to state. 199,698 men in UK Biobank followed a mean of 6.9 years, 5,402 diagnosed with and 295 dying from prostate cancer. Higher circulating IGF-1 was associated with prostate cancer diagnosis (hazard ratio 1.09 per 5 nmol/L increment, 95 percent CI 1.05 to 1.12) and with prostate cancer mortality (1.15, 1.02 to 1.29), with hazard ratios corrected for regression dilution using repeat measurements. A two-sample Mendelian randomisation analysis using genetic instruments and outcome data from 79,148 cases and 61,106 controls supported a causal role (cis-MR odds ratio 1.34 per 5 nmol/L, 1.07 to 1.68). This is an association study in men with naturally varying IGF-1, not a study of mecasermin, and it does not establish that treating a deficient child raises cancer risk.

      International Journal of Cancer, 2021· 199,698 peopleobserved only, nobody was given it

17. 17BNP and nesiritidePeptideStrong. At least two finished studies in people, and at least 1,000 people who took it. 3 completed trials, 7,149 people given it.4 reported

    nobody was given it1 watch-only study

    • Body weight does not change what this blood test tells a doctor. 686 people from the big nesiritide trial had the test done when they arrived. Heavier people had lower readings, as expected. A higher reading still predicted death within six months, whatever a person weighed. It did not predict anything at 30 days. This is the peptide used as a blood test rather than as a drug, and in that role it works.

      The numbers 686 patients from ASCEND-HF with NT-proBNP measured on admission. Higher body mass index was associated with lower concentrations, as expected, but body mass index did not modify the prognostic value: a raised admission NT-proBNP predicted 180 day mortality across every weight category, and predicted nothing at 30 days. This is the peptide used as a blood test rather than as a drug, and in that role it holds up.

      Journal of the American Heart Association, 2018· 686 peopleobserved only, nobody was given it

18. 18VIPPeptideLimited. People have taken it in a published study, but fewer than 100 of them. 1 completed trial, none stating how many people.2 reported

    nobody was given it1 watch-only study

    • The trial missed the thing it was built to answer. A hundred and ninety six people with critical COVID lung failure were given aviptadil into a vein or a dummy. By day 60, the share who were alive and off breathing support was no better on the drug. A separate look at survival alone leaned the drug's way. That was not the question the trial set out to settle, and a result found by looking again is a lead, not a finding.

      The numbers 196 patients: primary endpoint (alive and free of respiratory failure at day 60) not met; survival odds favored aviptadil in secondary analysis.

      Critical Care Medicine, 2022· 196 peopleobserved only, nobody was given it

19. 19Angiotensin IIPeptideModerate. At least one finished study in people, and at least 100 people who took it. 1 completed trial, 344 people given it.3 reported

    nobody was given it2 watch-only studies1 found nothing

    • found nothingIn real hospital use the people given this drug did worse, and that is probably because they were sicker. Doctors looked back at records for 147 patients in one intensive care unit who needed three or more blood pressure drugs. 56 of them were given angiotensin II. 86 percent of those patients died, against 71 percent of the rest. Nobody was picked by chance here. The drug went to the patients in the most trouble, so the two groups were never comparable.

      The numbers Retrospective single-centre cohort of 147 patients needing 3 or more vasopressors, 56 given angiotensin II. After propensity score weighting mortality was 86.0 percent with angiotensin II and 71.0 percent without, a difference that was not statistically significant (p = 0.16), and more angiotensin II patients still required 5 or more vasopressors (45.9 versus 12.5 percent, p < 0.01). Observational, and the sicker patients were the ones given the drug.

      Critical Care Explorations, 2022· 147 peopleobserved only, nobody was given it

    • This looked for the patients the drug might actually help, and found a candidate. Blood samples from the shock trial were tested for renin, a hormone that runs high when this system fails. Three quarters of the patients had high levels. Among those with the highest renin, far fewer died by day 28 on the drug than on the dummy. This is a look back inside one trial at a group picked after the fact. It points to a study someone should run, not to an answer.

      The numbers Analysis of the ATHOS-3 population examining baseline and follow-up renin concentrations against survival, testing whether renin identifies which patients respond.

      American Journal of Respiratory and Critical Care Medicine, 2020· number of people not givenobserved only, nobody was given it

20. 20GoserelinPeptidePreliminary. Studied in people, but no published study has had people take it. 2 human studies where nobody was given it.3 reported

    nobody was given it1 watch-only study

    • Adding three years of hormone treatment to radiotherapy roughly doubled the number of men still free of their cancer a decade later. Men with prostate cancer at high risk of spreading were split by chance into two groups. Ten years on, 47.7 percent of those given goserelin as well were alive and free of disease, against 22.7 percent of those who had radiotherapy alone. More of them were alive at all. Three years of it is a heavy price, and this result is why doctors accept it.

      The numbers Adding 3 years of goserelin to radiotherapy raised 10-year disease-free survival from 22.7% to 47.7% and improved overall survival.

      The Lancet Oncology, 2010· number of people not givenobserved only, nobody was given it

21. 21EndolutenPeptidePreliminary. Studied in people, but no published study has had people take it. 3 human studies where nobody was given it.8 reported

    nobody was given it1 watch-only study

    • A second study from the same institute, reporting the same kind of result, with the same piece missing. Older patients with heart disease were followed for 12 years. The authors say deaths were 28 percent lower on epithalamine, and that heart deaths, heart failure and chest infections each happened about half as often. The authors say people were put into groups by chance. It is once again their own preparation, in their own study, and no outside team has repeated it.

      The numbers A 12-year study in elderly patients with coronary disease and accelerated cardiovascular aging. Deaths in the epithalamine group were 28 percent lower than control, cardiovascular mortality was 2-fold lower, and the incidence of cardiovascular failure and respiratory disease was 2-fold lower. Reported as randomised by its authors. Again the institute's own work, again the injectable extract, again no outside replication.

      Bulletin of Experimental Biology and Medicine, 2006· number of people not givenobserved only, nobody was given it

    Also measured in animals or in the lab

    • found nothingIn fruit flies, mice and rats. A cow pineal gland extract helped these animals live longer on average, and lowered their death rate. In one mouse strain, the death rate did not change at all. This is the extract, not the capsule sold as Endoluten.

      The numbers Epithalamin, the bovine pineal extract, raised mean lifespan by 11 to 31 percent in female Drosophila, SHR mice, C3H/Sn mice and LIO rats. Ninety percent mortality and maximum lifespan rose in flies, C3H/Sn mice and rats. Mortality rate fell 52 percent in flies, 52 percent in rats and 27 percent in C3H/Sn mice, and did not change at all in SHR mice. Note the split: the effect was absent in one of the four mouse and rat groups tested.

      Mechanisms of Ageing and Development, 1998· animal study

Vitamins, minerals, amino acids and botanicals sold over the counter, held to the same standard.

1. 01TUDCASupplementLimited. People have taken it in a published study, but fewer than 100 of them. 3 completed trials, 54 people given it.7 reported

   0 people given it1 trial1 found nothing

   • found nothingThe trial behind the approval slowed decline slightly, and nothing else it measured moved. 137 people with ALS whose symptoms began within 18 months were split by chance, two to one, to the combination or a dummy. Nobody knew which. Function fell 1.24 points a month on the drug and 1.66 on the dummy, across 24 weeks. Every other measure, including strength, breathing and time to death, came out the same. Side effects were mainly stomach ones. The approval this supported was later withdrawn.

     The numbers CENTAUR, the phase 2 randomised trial of the fixed combination of sodium phenylbutyrate and taurursodiol, the form of TUDCA used in drug development. 137 people with ALS randomised 2 to 1, 89 to active and 48 to placebo, over 24 weeks. ALSFRS-R declined 1.24 points a month on drug against 1.66 on placebo, a difference of 0.42 points a month (95% CI 0.03 to 0.81, p = 0.03). The secondary outcomes did not differ significantly. Adverse events were mainly gastrointestinal. This functional result, together with post hoc survival analyses, supported the regulatory approval that was later withdrawn.

     New England Journal of Medicine, 2020· number of people not given

2. 02Vitamin DSupplementStrong. At least two finished studies in people, and at least 1,000 people who took it. 2 completed trials, 25,871 people given it.4 reported

   0 people given it1 trial1 found nothing

   • found nothingA second large test asked whether vitamin D helps people live longer, and it did not. Older Australian adults took a big dose once a month, or a dummy pill, for years. The same share died in each group, of any cause. If anything the treated group fared very slightly worse, by an amount too small to separate from chance. As in the trial above, the people getting the dummy already had reasonably good vitamin D levels. Nobody has tested a population that starts out genuinely deficient.

     The numbers Monthly high-dose vitamin D in older Australian adults. All-cause mortality hazard ratio 1.04. No benefit, again in a population whose placebo group averaged about 31 ng/mL.

     Lancet Diabetes and Endocrinology, 2022· number of people not given

   What people using it report

   • The blood level target is the central and unresolved disagreement. Some people aim at around 50 ng/mL or higher, others argue the mortality data favours lower, and a persistent minority argue that a low reading is a marker of poor health rather than something worth treating in itself.
   • Scepticism about the literature is loud and comes from both directions. One group argues most trials fail because they never measure the blood level achieved or account for cofactors, and another uses the newer large trials showing no mortality benefit to argue the whole practice is misplaced.
3. 03NiacinSupplementStrong. At least two finished studies in people, and at least 1,000 people who took it. 2 completed trials, 29,087 people given it.7 reported

   nobody was given it1 watch-only study1 found nothing

   • found nothingThis is the study niacin's reputation rests on, and it is weaker than the reputation. 8,341 men who had already had a heart attack were treated between 1966 and 1975, long before statins existed. During the trial, niacin slightly cut repeat heart attacks and did not cut deaths at all. Fifteen years later, almost nine years after everyone had stopped, about 52 in every hundred niacin men had died against 58 on the dummy. That gap was found by watching afterwards, not by the trial itself.

     The numbers The historical result that kept niacin in the guidelines for thirty years, and it is weaker than its reputation. In the Coronary Drug Project, 8,341 men aged 30 to 64 with a previous myocardial infarction were treated between 1966 and 1975. Niacin modestly reduced definite non-fatal recurrent myocardial infarction but did not reduce total mortality during the trial. At a mean follow-up of 15 years, nearly 9 years after the drug was stopped, all-cause mortality was 52.0 percent on niacin versus 58.2 percent on placebo, 11 percent lower, P=0.0004. This is a post-trial observational mortality difference in a pre-statin population, not a result obtained on top of modern therapy, and both AIM-HIGH and HPS2-THRIVE tested niacin on top of modern therapy and found nothing.

     Journal of the American College of Cardiology, 1986· 8,341 peopleobserved only, nobody was given it

4. 04ErgothioneineSupplementPreliminary. Studied in people, but no published study has had people take it. 1 human study where nobody was given it.1 reported

   nobody was given it1 watch-only study

   • Nobody was given anything here. Researchers measured this compound in the blood of more than three thousand adults, then watched what happened to them over the next twenty one years. People with more of it were less likely to develop heart disease and less likely to die of anything. That is an association. People with higher levels eat differently and live differently in other ways too. It is a reason to run a trial. It is not evidence that taking it helps.

     The numbers 3,236 adults followed 21 years: higher plasma ergothioneine independently predicted lower coronary disease, cardiovascular and overall mortality.

     Heart, 2020· 3,236 peopleobserved only, nobody was given it

5. 05CoQ10SupplementModerate. At least one finished study in people, and at least 100 people who took it. 2 completed trials, 162 people given it.4 reported

   nobody was given it1 watch-only study

   • Coenzyme Q10 cut deaths and hospital admissions in people with serious heart failure. Four hundred and twenty patients took it three times a day, or a dummy, for two years. Nobody involved knew which. Major heart events struck 15 percent of the treated group against 26 percent on the dummy, and about half as many died. The first sixteen weeks showed nothing at all, so the benefit only appeared with time. This is one trial of moderate size and it has not been repeated at this scale.

     The numbers 420 patients with moderate to severe chronic heart failure, 100 mg three times daily, two years. Major adverse cardiovascular events 15% against 26%, hazard ratio 0.50 (95% CI 0.32 to 0.80, p = 0.003). Cardiovascular mortality 9% against 16% (p = 0.026) and all-cause mortality 10% against 18% (p = 0.018). The short-term 16-week endpoints were null.

     JACC Heart Failure, 2014· 420 peopleobserved only, nobody was given it

6. 06TaurineSupplementModerate. At least one finished study in people, and at least 100 people who took it. 1 completed trial, 120 people given it.5 reported

   nobody was given it1 watch-only study1 found nothing

   • found nothingThe idea that taurine falls as you get older did not hold up when government researchers went looking. Nobody was given anything here. A team at the National Institute on Aging measured the same people over time in three separate groups, and did the same in monkeys and in mice. Taurine went up with age, or stayed flat. It did not fall. The 2023 paper that turned taurine into a longevity story was built on the assumption that it falls.

     The numbers From the National Institute on Aging intramural programme. Measured longitudinally across three human cohorts, nonhuman primates and mice, taurine increased or stayed unchanged with age, contradicting the decline premise the 2023 lifespan paper rests on.

     Science, 2025· number of people not givenobserved only, nobody was given it

   Also measured in animals or in the lab

   • In mice: middle-aged mice given taurine lived 10 to 12 percent longer. In yeast, it made no difference. The monkey part ran 6 months and did not measure lifespan. The human part only compared blood levels across people at one point in time. It did not test taking taurine.

     The numbers The paper that made taurine a longevity story. Middle-aged C57BL/6J mice given 1,000 mg/kg/day lived 10 to 12 percent longer at the median. The yeast arm showed no lifespan effect. The rhesus monkey arm ran 6 months and had no lifespan data. The human piece was a cross-sectional association in EPIC-Norfolk, not a trial.

     Science, 2023· animal study

7. 07Low-dose lithiumSupplementModerate. At least one finished study in people, and at least 100 people who took it. 3 completed trials, 106 people given it.5 reported

   nobody was given it1 watch-only study

   • Nobody was given anything in the human half of this paper, and the other half is a worm. Researchers compared how much lithium was in the tap water across 18 neighbouring Japanese municipalities covering 1,206,174 people, and found that places with more of it had fewer deaths. That is a pattern across places, not an effect in a person. Separately, they put roundworms in a similar lithium concentration and the worms lived longer. Towns differ from each other in dozens of ways nobody measured here.

     The numbers Two separate pieces of work in one short paper. An observational weighted regression across 18 neighbouring Japanese municipalities totalling 1,206,174 individuals found an inverse correlation between tap water lithium concentration and all-cause mortality (beta -0.661, p = 0.003). Separately, exposing Caenorhabditis elegans to a comparably low lithium chloride concentration extended lifespan (p = 0.047). The human half is an ecological correlation between places, not an intervention in people, and the lifespan half is a worm.

     European Journal of Nutrition, 2011· number of people not givenobserved only, nobody was given it

8. 08Alpha-ketobutyrateSupplementPreliminary. Studied in people, but no published study has had people take it. 2 human studies where nobody was given it.3 reported

   nobody was given it1 watch-only study

   • In people, this chemical marks metabolic trouble rather than health. Researchers screened the blood chemistry of people without diabetes and found alpha-hydroxybutyrate, which the body makes from alpha-ketobutyrate, rising early in insulin resistance and poor glucose handling. Nobody was given anything here. This is the human setting the lifespan claim has to sit inside. In humans, this branch of metabolism runs high in the people heading toward metabolic disease, not in the ones staying well.

     The numbers The metabolomic screen that identified alpha-hydroxybutyrate, the reduction product of alpha-ketobutyrate, as an early marker of insulin resistance and glucose intolerance in non-diabetic people. This is the human context that the lifespan claim sits inside: in people, this branch of metabolism is elevated in the direction of metabolic disease rather than health.

     PLoS One, 2010· number of people not givenobserved only, nobody was given it

9. 09Omega-3SupplementStrong. At least two finished studies in people, and at least 1,000 people who took it. 3 completed trials, 34,050 people given it.4 reported

   nobody was given it1 watch-only study

   • People with more omega-3 in their blood died less often, but nobody was given anything. Researchers pooled seventeen studies that simply followed people over time and measured what was already in their blood. Those in the top fifth for blood omega-3 had roughly 15 to 18 percent lower death rates than those in the bottom fifth. This was watching, not testing. Nobody was assigned a supplement. A blood level reflects diet, wealth and general health at once, so it cannot tell you what a capsule would do.

     The numbers Pooled across 17 prospective cohorts. The highest blood omega-3 quintile carried roughly 15 to 18% lower mortality than the lowest. Observational, and the exposure is a measured blood level rather than a supplement taken.

     Nature Communications, 2021· number of people not givenobserved only, nobody was given it

Approved drugs, biologics and hormones that have been measured for this. They are here because leaving them out would misrepresent the evidence, and they are below the peptides because that is not what most people come here to read.

1. 01SimvastatinSmall moleculeStrong. At least two finished studies in people, and at least 1,000 people who took it. 2 completed trials, 24,980 people given it.6 reported

   24,980 people given it2 trials

   • The benefit held even in people whose cholesterol already looked normal. 20,536 UK adults aged 40 to 80 with clogged arteries or diabetes were split by chance. One group took 40 mg of simvastatin a day, the other took a dummy pill. 14.7 percent of the dummy group died of any cause, against 12.9 percent on the drug. Heart attacks, strokes and similar events fell from about a quarter of people to a fifth. Muscle damage did happen, in roughly one person in ten thousand each year.

     The numbers 20,536 UK adults aged 40 to 80 with coronary, other occlusive arterial disease or diabetes, randomised to 40 mg simvastatin daily or placebo. All-cause mortality 12.9 percent versus 14.7 percent (p equals 0.0003). Major vascular events fell 24 percent, from 25.2 percent to 19.8 percent. Benefit held even in participants entering with LDL cholesterol below 3.0 mmol/L. The annual excess risk of myopathy was about 0.01 percent.

     Lancet, 2002· 20,536 peoplepoints the wrong way

   • Lowering cholesterol with a statin kept people alive, and this is the trial that showed it. 4,444 people who already had chest pain or a previous heart attack were split by chance into two groups. One took simvastatin, the other a dummy pill, and both were followed for over five years. By the end, 12 percent of the dummy group had died against 8 percent on the drug. Deaths from heart disease fell from 189 to 111. Everyone here already had heart disease, so this says nothing about healthy people.

     The numbers 4,444 people with angina or previous myocardial infarction, randomised double-blind, median follow-up 5.4 years. 256 placebo patients (12 percent) died against 182 on simvastatin (8 percent), relative risk of death 0.70 (95 percent CI 0.58 to 0.85, p equals 0.0003). Coronary deaths fell from 189 to 111. Major coronary events occurred in 28 percent on placebo and 19 percent on simvastatin.

     Lancet, 1994· 4,444 people

   Also measured in animals or in the lab

   • found nothingIn mice. Simvastatin mixed into food at two doses did not change how long male or female mice lived. Resveratrol did nothing either. In the same test, rapamycin started at 9 months made mice live longer, on average 10 percent for males and 18 percent for females, at each of three labs.

     The numbers Interventions Testing Program. Simvastatin at 12 and 120 ppm in the diet had no significant effect on survival in male or female mice. Resveratrol at 300 and 1200 ppm also had none. In the same cohort rapamycin, started at 9 months, extended median survival by an average of 10 percent in males and 18 percent in females, including maximum life span, at each of three test sites.

     Journals of Gerontology Series A, 2011· animal study

2. 02Cardiac glycosidesSmall moleculeModerate. At least one finished study in people, and at least 100 people who took it. 1 completed trial, 6,800 people given it.

   6,800 people given it1 trial1 found nothing

   • found nothingDigoxin did not save lives, and it was tested well enough to say so. 6,800 people with weak hearts took digoxin or a dummy pill and were followed about three years on average. About the same share died in each group, roughly 35 percent either way. A study this big would have found a survival benefit if there was one. Digoxin did keep people out of hospital: heart failure stays fell from about 35 percent to 27 percent. This is heart failure proof. It says nothing about ageing.

     The numbers 6,800 patients with heart failure and ejection fraction 0.45 or less randomised to digoxin or placebo, average follow-up 37 months. Mortality unchanged: 1,181 deaths (34.8 percent) versus 1,194 (35.1 percent), risk ratio 0.99, 95 percent confidence interval 0.91 to 1.07. Hospitalisation for worsening heart failure fell from 34.7 to 26.8 percent, risk ratio 0.72. This is cardiology evidence and says nothing about senescence.

     New England Journal of Medicine, 1997· 6,800 people

3. 03EmpagliflozinSmall moleculeStrong. At least two finished studies in people, and at least 1,000 people who took it. 3 completed trials, 16,738 people given it.4 reported

   5,988 people given it1 trial, 1 watch-only

   • It slowed kidney disease down, and it did not stop people dying. 6,609 people with chronic kidney disease were followed for two years. Their kidney disease got worse, or they died of heart disease, in 16.9 percent of the dummy group against 13.1 percent on empagliflozin. Deaths from any cause were 5.1 percent against 4.5 percent, a gap too small to separate from chance. Anyone treating this drug as something that makes people live longer should stop at that last sentence.

     The numbers EMPA-KIDNEY. 6,609 people with chronic kidney disease, median 2.0 years. Kidney disease progression or cardiovascular death occurred in 13.1 percent against 16.9 percent (hazard ratio 0.72). Notably for anyone reading the drug as a mortality intervention, death from any cause was 4.5 percent against 5.1 percent and was not a significant difference in this trial.

     New England Journal of Medicine, 2023· 6,609 peopleobserved only, nobody was given it

   • It helped the harder kind of heart failure, mostly by keeping people out of hospital. 5,988 people whose hearts still pumped reasonably well but who had heart failure symptoms were followed for a bit over two years. 17.1 percent of the dummy group died of heart disease or were admitted for heart failure. On empagliflozin, 13.8 percent were. The authors say the difference came mainly from fewer hospital admissions rather than from fewer deaths. That distinction matters to anyone reading this as a life-extending drug.

     The numbers EMPEROR-Preserved. 5,988 people with class II to IV heart failure and an ejection fraction above 40 percent, median 26.2 months. Cardiovascular death or heart failure hospitalisation occurred in 13.8 percent against 17.1 percent (hazard ratio 0.79). The authors state the effect was mainly driven by fewer heart failure hospitalisations rather than fewer deaths.

     New England Journal of Medicine, 2021· 5,988 people

   Also measured in animals or in the lab

   • In mice. Naturally old male mice given empagliflozin lived 5.9 percent longer on average. They also did better on learning, memory and balance tests, weighed less, and showed fewer signs of worn-out cells in the liver. Their gut bacteria changed too. This is one lab's study, and nobody else has repeated it.

     The numbers The entire mouse lifespan case, from one laboratory. Empagliflozin extended the median survival of male mice by 5.9 percent, improved learning, memory and motor balance, lowered body weight, reduced hepatic P21 and P16, altered gut flora composition and raised short-chain fatty acids. A single-site study, not part of any multi-site replication programme.

     GeroScience, 2024· animal study

   • In mice. This is a different drug, canagliflozin, not empagliflozin. In the government mouse program, male mice given it in their food from 7 months old lived 14 percent longer on average. The longest-lived males lived 9 percent longer. It worked at all three test labs. Female mice got no benefit. Crediting this result to empagliflozin is a common mistake.

     The numbers This is the Interventions Testing Program SGLT2 result, and it is canagliflozin, not empagliflozin. Canagliflozin at 180 ppm in chow from 7 months of age extended median male survival by 14 percent and raised the 90th percentile survival age by 9 percent, with parallel effects at all three test sites. No lifespan benefit in females. Attributing this result to empagliflozin is a factual error that circulates widely.

     JCI Insight, 2020· animal study

4. 04PioglitazoneSmall moleculeStrong. At least two finished studies in people, and at least 1,000 people who took it. 2 completed trials, 9,114 people given it.5 reported

   3,876 people given it1 trial

   • In people with insulin resistance but no diabetes who had just had a stroke or a mini-stroke, pioglitazone lowered the chance of another stroke or a heart attack over about five years. It also halved new diabetes. It cost more weight gain, swelling and broken bones. Death rates were about the same.

     The numbers 3,876 patients without diabetes, with insulin resistance and a recent ischaemic stroke or TIA, randomised to pioglitazone (target 45 mg daily) or placebo, median 4.8 years (IRIS). Stroke or myocardial infarction in 9.0% versus 11.8% (HR 0.76, 95% CI 0.62 to 0.93, p=0.007). Diabetes in 3.8% versus 7.7% (HR 0.48). All-cause mortality similar (HR 0.93). Weight gain over 4.5 kg 52.2% versus 33.7%, oedema 35.6% versus 24.9%, fracture needing surgery or hospitalisation 5.1% versus 3.2%.

     The New England Journal of Medicine, 2016· 3,876 people

   Also measured in animals or in the lab

   • In mice. The NIA mouse lifespan program tested eleven compounds at three labs. None clearly made male or female mice live longer. In females, pooling all labs, astaxanthin, late-start mitoglitazone and pioglitazone were linked to clearly shorter lives. With one lab left out, where untreated females lived unusually long, the harm held for mitoglitazone and pioglitazone only.

     The numbers Interventions Testing Program, eleven compounds in UM-HET3 mice across three sites. None significantly increased lifespan in male or female mice. In females, pooling all sites, astaxanthin, late-start mitoglitazone and pioglitazone were associated with significantly reduced lifespan. After excluding one site whose control females lived unusually long, the negative effect remained for mitoglitazone and pioglitazone only.

     GeroScience, 2026· animal study

5. 05Zoledronic acidSmall moleculeStrong. At least two finished studies in people, and at least 1,000 people who took it. 4 completed trials, 7,176 people given it.

   3,065 people given it2 trials

   • The bone drip prevented broken bones in older women with thinning bones. Two thousand New Zealand women aged 65 and over got four infusions of either the drug or plain salt water over six years, spaced eighteen months apart. Fragility fractures happened in 122 women on the drug and 190 on salt water. Roughly fifteen women had to be treated for one to avoid a fracture. The trial was built to count fractures, not deaths, so it cannot tell you whether anyone lived longer.

     The numbers 2,000 New Zealand women aged 65 or older with osteopenia, randomised to four infusions of 5 mg zoledronate or saline at 18-month intervals over six years. Fragility fracture occurred in 190 on placebo and 122 on zoledronate, hazard ratio 0.63 (95 percent CI 0.50 to 0.79). Number needed to treat 15. This is the large trial in older women, and its primary endpoint was fracture, not mortality.

     New England Journal of Medicine, 2018· 2,000 people

   • A once a year bone drip after a broken hip cut later fractures, and fewer people died. Around two thousand people, average age in their mid seventies, got the drip or a dummy one within three months of hip surgery, then were followed about two years. New fractures hit about 9 in every hundred on the drug and about 14 on the dummy. Deaths fell too, roughly a quarter fewer. Death was not what the trial was built to measure. Fever and aching muscles were the usual side effects.

     The numbers HORIZON Recurrent Fracture Trial, NCT00046254. 1,065 assigned to yearly 5 mg intravenous zoledronic acid and 1,062 to placebo within 90 days of hip fracture repair, mean age 74.5, median follow-up 1.9 years. Primary endpoint new clinical fracture: 8.6 percent against 13.9 percent, a 35 percent reduction. In the safety analysis 101 of 1,054 (9.6 percent) on drug and 141 of 1,057 (13.3 percent) on placebo died, a 28 percent reduction in all-cause death, p equals 0.01. Mortality was not the primary endpoint. Commonest adverse events were pyrexia, myalgia and bone and musculoskeletal pain; no osteonecrosis of the jaw was reported.

     New England Journal of Medicine, 2007· 1,065 people

   Also measured in animals or in the lab

   • In human lung cells and mouse cells in a dish, and in old mice. Zoledronic acid killed zombie cells while barely touching healthy ones. In old mice, eight weeks of it cut inflammatory signals in the blood and improved grip strength. It does not test whether it helps people live longer.

     The numbers Mayo Clinic. In human lung fibroblasts and DNA-repair-deficient mouse embryonic fibroblasts, zoledronic acid killed senescent cells with minimal effect on non-senescent cells. In aged mice treated for eight weeks it significantly reduced circulating SASP factors including CCL7, IL-1 beta, TNFRSF1A and TGF beta 1, and improved grip strength. Cell and mouse work proposing a senolytic or senomorphic mechanism for the non-skeletal effects; it does not test the mortality question in people.

     Aging (Albany NY), 2023· animal study

6. 06EnalaprilSmall moleculeStrong. At least two finished studies in people, and at least 1,000 people who took it. 2 completed trials, 2,822 people given it.5 reported

   2,822 people given it2 trials, 1 watch-only1 found nothing

   • found nothingIn people with no symptoms, enalapril did not clearly save lives. 4,228 people with a weak pumping heart but no symptoms took enalapril or a dummy pill for about three years. 313 died on enalapril against 334 on the dummy pill, a gap small enough to be chance. A study this size would likely have found a real survival gain if there was one. It did delay heart failure. For anyone reading enalapril as a longevity drug, this is the result that matters, and it came up empty.

     The numbers 4,228 asymptomatic people with ejection fraction 0.35 or below, mean follow-up 37.4 months. Total mortality 313 versus 334 deaths, risk reduction 8 percent (95 percent CI -8 to 21, p = 0.30), not significant. Death or development of heart failure 630 versus 818 (29 percent reduction, p < 0.001). The null mortality result in people without symptoms is the relevant one for anyone reading enalapril as a longevity drug.

     New England Journal of Medicine, 1992· 4,228 peopleobserved only, nobody was given it

   • In people with symptoms, enalapril kept more of them alive. 2,569 patients with heart failure and a weak pumping heart took enalapril or a dummy for about three and a half years on average. 452 died on enalapril against 510 on the dummy, roughly a sixth fewer deaths. Hospital admissions for heart failure fell further still. A United States government institute ran it, not a drug company. A large trial, and a real but moderate benefit.

     The numbers 2,569 patients with symptomatic heart failure and ejection fraction 0.35 or below, enalapril 2.5 to 20 mg a day or placebo, mean follow-up 41.4 months. Deaths 452 (35.2 percent) versus 510 (39.7 percent), risk reduction 16 percent (95 percent CI 5 to 26, p = 0.0036); death or heart failure hospitalisation 613 versus 736 (26 percent reduction). Run by the US National Heart, Lung, and Blood Institute.

     New England Journal of Medicine, 1991· 2,569 people

   • This is one of the clearest survival gains ever shown for a pill. 253 patients with the worst kind of heart failure got enalapril or a dummy pill on top of their usual treatment, and nobody involved knew which. At six months, 26% of the enalapril group had died against 44% on the dummy pill. Every life saved came from slowing the heart failure itself, not from preventing sudden death. Seven people stopped for low blood pressure, and none on the dummy pill.

     The numbers 253 patients with NYHA class IV heart failure, double-blind, enalapril 2.5 to 40 mg a day or placebo on top of conventional therapy. Six-month mortality 26 versus 44 percent (40 percent reduction, p = 0.002); one-year 31 percent reduction; 50 versus 68 deaths overall (27 percent). Entire benefit in progressive heart failure deaths, none in sudden death. Hypotension withdrawals 7 versus 0. Funding not stated in the abstract retrieved.

     New England Journal of Medicine, 1987· 253 people

   Also measured in animals or in the lab

   • found nothingIn mice. A second look at 132 comparisons from the NIA mouse lifespan program, 2004 to 2022. Enalapril at 120 ppm from 4 months, 170 treated males against 357 untreated: typical male lifespan rose 7 percent. The standard test said that could be chance. The Gehan test, which counts early deaths more, said it held up. Females showed nothing. No adjustment for running so many tests was reported. The authors say the benefit is limited to midlife. Public NIA money paid for it.

     The numbers Reanalysis of 132 ITP comparisons from 2004 to 2022. Enalapril 120 ppm from 4 months, 170 treated males against 357 controls: median lifespan +7 percent, log-rank p = 0.22 (not significant), Gehan p = 0.046, proportional hazards assumption violated. No female effect. No multiplicity correction reported. The authors describe the benefit as limited to midlife. NIA funded.

     GeroScience, 2024· animal study

   • In mice. This is the NIA mouse lifespan program report best known for its rapamycin result. In the same run, enalapril and CAPE did not clearly make male or female mice live longer by the standard test. Public NIA money paid for it.

     The numbers The ITP report whose cohort included enalapril and CAPE as agents that did not significantly extend lifespan by log-rank test in either sex, alongside the landmark rapamycin result. NIA funded.

     Nature, 2009· animal study

7. 07TrametinibSmall moleculeStrong. At least two finished studies in people, and at least 1,000 people who took it. 2 completed trials, 1,192 people given it.

   1,192 people given it2 trials

   • After surgery for stage III melanoma with a BRAF mutation, a year of trametinib plus dabrafenib cut the chance of the cancer coming back compared with a dummy pill. This is a two-drug result, not trametinib alone.

     The numbers 870 patients with resected stage III BRAF V600E or V600K melanoma randomised double-blind to dabrafenib 150 mg twice daily plus trametinib 2 mg daily, or placebo, for 12 months (COMBI-AD). Three-year relapse-free survival 58% versus 39% (HR 0.47, 95% CI 0.39 to 0.58). Three-year overall survival 86% versus 77% (HR 0.57), short of the prespecified interim boundary.

     The New England Journal of Medicine, 2017· 870 people

   • In advanced melanoma with a BRAF mutation, trametinib on its own held the cancer back longer than chemotherapy and more people were alive at six months. Rash, diarrhoea and swelling were the common side effects. This is the trial that led to its approval as a single drug.

     The numbers 322 patients with metastatic melanoma carrying a BRAF V600E or V600K mutation randomised 2:1 to trametinib 2 mg daily or chemotherapy, open-label (METRIC). Median progression-free survival 4.8 versus 1.5 months (HR 0.45, 95% CI 0.33 to 0.63). Overall survival at 6 months 81% versus 67% despite crossover (HR 0.54). Rash, diarrhoea and peripheral oedema were most common; reductions in ejection fraction and eye effects were infrequent.

     The New England Journal of Medicine, 2012· 322 people

8. 08HydralazineSmall moleculeStrong. At least two finished studies in people, and at least 1,000 people who took it. 3 completed trials, 1,724 people given it.4 reported

   642 people given it1 trial

   • Adding hydralazine plus a nitrate to standard heart failure treatment lowered deaths over two years in 642 men. At two years, 25.6% had died on the pair against 34.3% on a dummy pill. It was the first trial of a blood vessel relaxing drug to show people living longer. It is a two-drug result, not hydralazine alone.

     The numbers 642 men with chronic heart failure on digoxin and a diuretic randomised double-blind to placebo, prazosin 20 mg daily, or hydralazine 300 mg plus isosorbide dinitrate 160 mg daily, mean follow-up 2.3 years. Two-year mortality 25.6% on hydralazine-nitrate versus 34.3% on placebo, a 34% risk reduction (p<0.028); 36.2% versus 46.9% at three years. Prazosin no different from placebo. Ejection fraction rose at 8 weeks and 1 year on the combination only.

     The New England Journal of Medicine, 1986· 642 people

9. 09BPTESSmall moleculeModerate. At least one finished study in people, and at least 100 people who took it. 2 completed trials, 513 people given it.1 reported

   513 people given it2 trials

   • The only proper test of blocking this enzyme in people found nothing. 444 adults with advanced kidney cancer got telaglenastat plus the cancer drug cabozantinib, or a dummy pill plus cabozantinib. Both groups went about 9.2 and 9.3 months before their cancer grew again. That is the same result twice. Telaglenastat is a different drug from BPTES, but it hits the same target, and this is cancer medicine, not ageing. The maker paid for the study.

     The numbers The only randomised human data on glutaminase inhibition. 444 patients with metastatic renal cell carcinoma. Median progression-free survival 9.2 months with telaglenastat plus cabozantinib versus 9.3 months with placebo plus cabozantinib, hazard ratio 0.94, P = 0.65. Manufacturer funded. Oncology, not senescence.

     JAMA Oncology, 2022· 444 people

   • A smaller study leaned toward the drug without settling anything. 69 adults with advanced kidney cancer got telaglenastat or a dummy pill, both along with the cancer drug everolimus. Two got the drug for every one on the dummy pill. Cancer took 3.8 months to grow again on the drug, against 1.9 months. The bar for success was set loose, so this would not count as proof elsewhere. Serious side effects hit 74 percent against 61 percent. The maker paid for it.

     The numbers 69 patients randomised 2:1. Median progression-free survival 3.8 months versus 1.9 months, hazard ratio 0.64, one-sided P = 0.079 against a pre-specified one-sided alpha below 0.2. Grade 3 to 4 events in 74 percent versus 61 percent. Manufacturer funded.

     Clinical Cancer Research, 2022· 69 people

   Also measured in animals or in the lab

   • In mice and in human cells in a dish. Worn-out human cells needed the glutaminase enzyme to survive. Leaky internal compartments make them acidic inside, and the enzyme makes ammonia that cancels the acid out. Blocking it in old mice killed worn-out cells and eased age-related organ problems.

     The numbers Human cells and mice. GLS1 was identified as essential for the survival of human senescent cells: lysosomal damage lowers intracellular pH, inducing kidney-type glutaminase, whose ammonia production neutralises the acidity. Inhibiting it in aged mice eliminated senescent cells specifically and ameliorated age-associated organ dysfunction.

     Science, 2021· animal study

10. 10TelaglenastatSmall moleculeModerate. At least one finished study in people, and at least 100 people who took it. 3 completed trials, 513 people given it.1 reported

    513 people given it2 trials1 found nothing

    • found nothingTelaglenastat was tested properly in a large study, and it did not work. 444 adults with advanced kidney cancer took telaglenastat or a dummy pill, both along with the cancer drug cabozantinib. The cancer grew again after 9.2 months on the drug and 9.3 months on the dummy pill. Tumours shrank in 31 percent against 28 percent, the same answer. Serious side effects were common in both groups, 71 percent against 79 percent. The maker paid for it.

      The numbers 444 patients randomised, double blind, placebo controlled. Median progression-free survival 9.2 versus 9.3 months, hazard ratio 0.94, 95 percent confidence interval 0.74 to 1.21, P = 0.65. Overall response 31 versus 28 percent. Grade 3 to 4 adverse events in 71 versus 79 percent. Manufacturer funded. The primary endpoint was missed.

      JAMA Oncology, 2022· 444 people

    • A second, smaller study hinted at a benefit and proved nothing. 69 adults with advanced kidney cancer, most already through three treatments, got telaglenastat or a dummy pill, both along with the cancer drug everolimus. Two got the drug for every one on the dummy pill. The cancer grew again after 3.8 months against 1.9 months. One tumour shrank. The study set itself a low bar and still did not clear it cleanly. Serious side effects hit 74 percent against 61 percent. The maker paid for it.

      The numbers 69 patients randomised 2:1 after a median of three prior lines. Median progression-free survival 3.8 versus 1.9 months, hazard ratio 0.64, 95 percent confidence interval 0.34 to 1.20, one-sided P = 0.079 against a pre-specified one-sided alpha below 0.2. One partial response on telaglenastat. Grade 3 to 4 events 74 versus 61 percent. Manufacturer funded.

      Clinical Cancer Research, 2022· 69 people

    Also measured in animals or in the lab

    • In mice and in human cells in a dish. Worn-out cells needed the glutaminase enzyme to survive. Blocking it in old mice killed worn-out cells and eased age-related organ problems. This is why telaglenastat shows up on lists of clean-up drugs. It is a mouse result.

      The numbers Mouse and human cells. The senolytic rationale for this drug class: glutaminase 1 is required for senescent cell survival, and inhibiting it in aged mice eliminated senescent cells and improved age-associated organ dysfunction. This is why telaglenastat appears on senolytic lists. It is a mouse result.

      Science, 2021· animal study

11. 11Azithromycin and roxithromycinSmall moleculeModerate. At least one finished study in people, and at least 100 people who took it. 1 completed trial, 480 people given it.

    480 people given it1 trial, 1 watch-only

    • This trial was stopped early because the antibiotic was harming people. 480 people who had received a donor stem cell transplant took low dose azithromycin three times a week or a dummy pill for two years. The safety board halted it when cancer relapses piled up in the antibiotic group. Two years in, more of that group had relapsed and fewer were alive. Lung function was no better either. Long term low dose azithromycin did worse than nothing.

      The numbers 480 patients randomised to 250 mg azithromycin three times weekly or placebo for two years after allogeneic transplant. Stopped early in December 2016 after the safety board detected an imbalance in haematological relapses. Two-year airflow decline-free survival 32.8 percent on azithromycin against 41.3 percent on placebo (hazard ratio 1.3). Two-year survival 56.6 percent against 70.1 percent (hazard ratio 1.5, 95 percent CI 1.1 to 2.0). Two-year cumulative haematological relapse 33.5 percent against 22.3 percent. Long-term low-dose azithromycin produced worse outcomes than placebo.

      JAMA, 2017· 480 people

    • Five days of azithromycin was linked to more heart deaths, though the extra risk to any one person is small. Researchers combed Tennessee Medicaid records and compared people taking the antibiotic against people taking no antibiotic. Death from heart causes was roughly three times as common during the five days of treatment. Amoxicillin showed no such rise. In real counts that is about 47 extra heart deaths for every million courses. Nobody was given anything here. Researchers only watched records.

      The numbers Tennessee Medicaid cohort. During five days of azithromycin, compared with no antibiotics, risk of cardiovascular death rose (hazard ratio 2.88, 95 percent CI 1.79 to 4.63) and of death from any cause (1.85, 1.25 to 2.75). Amoxicillin showed no such increase. Estimated 47 additional cardiovascular deaths per million courses, and 245 per million in the highest cardiovascular risk decile. An observational cohort, not a randomised trial, and the absolute risk is small.

      New England Journal of Medicine, 2012· number of people not givenobserved only, nobody was given it

12. 12MinocyclineSmall moleculeModerate. At least one finished study in people, and at least 100 people who took it. 2 completed trials, 966 people given it.

    412 people given it1 trial

    • This drug did not simply fail in ALS. People got worse on it. 412 patients were split by chance to a dummy pill or minocycline built up to 400 mg a day for nine months. Those on minocycline lost physical function faster than those on the dummy. Breathing capacity, muscle strength and deaths all leaned the wrong way too, though those gaps were small enough to be chance. The authors called the effect harmful and said it should change how the drug is tested in other brain diseases.

      The numbers 412 patients randomised to placebo or escalating minocycline up to 400 mg per day for nine months. ALSFRS-R deterioration was faster on minocycline, -1.30 against -1.04 units per month (p equals 0.005), with non-significant trends toward faster decline in forced vital capacity and muscle testing and greater mortality (hazard ratio 1.32). The authors concluded minocycline had a harmful effect with implications for its trials in other neurological disorders.

      Lancet Neurology, 2007· 412 peoplepoints the wrong way

    Also measured in animals or in the lab

    • In mice. This test run was built around giving rapamycin late in life, from 20 months. Rapamycin made male and female mice live longer. Four other drugs were tested the same way, including minocycline. None of them changed how long mice lived, in either sex.

      The numbers Interventions Testing Program cohort comparing three late-life rapamycin regimens started at 20 months. Rapamycin at 42 ppm increased survival in both sexes. The same experimental design tested four other drugs, minocycline, beta-guanidinopropionic acid, MitoQ and 17-DMAG, and none of these led to a change in survival in either sex.

      Aging Cell, 2020· animal study

13. 13MetforminSmall moleculeModerate. At least one finished study in people, and at least 100 people who took it. 3 completed trials, 489 people given it.6 reported

    342 people given it1 trial, 3 watch-only

    • The longest follow-up in people we have found no drop in deaths. 3234 adults at high risk of diabetes were given metformin, an intensive lifestyle program, or a dummy pill. After a median 21 years, 453 had died. Neither metformin nor lifestyle cut deaths from any cause, cancer or heart disease. Preventing diabetes and preventing death were different questions, and only the first one moved.

      The numbers DPP and DPPOS. 3,234 adults at high risk for type 2 diabetes, median 21 years. 453 deaths. Neither metformin nor lifestyle reduced all-cause, cancer or cardiovascular mortality.

      Diabetes Care, 2021· 3,234 peopleobserved only, nobody was given it

    • This is the diabetes study that made metformin a first-choice drug, not a longevity study. 342 overweight adults with new type 2 diabetes took metformin, and 411 stayed on diet as the main plan. They were followed for a median of 10.7 years. Deaths from any cause were 36 percent lower on metformin. A second part of the paper added metformin to the top dose of a sulphonylurea pill, and it pointed the other way on diabetes deaths. Nobody here was a healthy adult taking it to age slower.

      The numbers UKPDS 34. 342 overweight adults with newly diagnosed type 2 diabetes randomised to metformin versus 411 on conventional diet policy, median 10.7 years. All-cause mortality risk reduction 36% (95% CI 9 to 55). A supplementary randomisation adding metformin to maximum sulphonylurea found a higher risk of diabetes-related death. Not a trial in people without diabetes.

      Lancet, 1998· 342 peoplepoints the wrong way

    • The Danish try at repeating the 2014 survival claim found the opposite. People who started metformin for type 2 diabetes died more often than matched people without diabetes, including inside twin pairs. After other factors were counted, the extra risk was still there. Comparing people who already have diabetes with people who do not cannot show that the drug lengthens life.

      The numbers Danish registry analysis, 1996 to 2012. Incident metformin monotherapy versus no diabetes was associated with higher mortality in singletons (adjusted IRR 1.32, 95% CI 1.16 to 1.50) and in discordant twins (adjusted IRR 1.64, 95% CI 1.10 to 2.46).

      International Journal of Epidemiology, 2022· number of people not givenobserved only, nobody was given itpoints the wrong way

    • Twenty years of Welsh records tell the same story. 129140 people on metformin for type 2 diabetes did not outlive matched people without diabetes. An early bump in the first three years reversed after five. A short window can manufacture a longevity claim that a long window erases.

      The numbers Welsh SAIL records. 129,140 metformin-treated type 2 diabetes patients versus matched non-diabetic controls. Over a twenty-year window metformin patients had shorter survival than controls. An apparent benefit in the first three years reversed after five.

      BMC Public Health, 2023· number of people not givenobserved only, nobody was given it

    Also measured in animals or in the lab

    • In mice: a 2013 study in one strain of mice found metformin improved health and lifespan. The US government's multi-site ageing test program, using mixed-breed mice, did not find a real lifespan gain in males or females.

      The numbers The positive mouse result that launched metformin's longevity reputation, in C57BL/6 mice. The multi-site Interventions Testing Program, using genetically heterogeneous mice specifically to catch results that do not travel, did not reproduce a significant lifespan effect in either sex.

      Nature Communications, 2013· animal study

14. 14RuxolitinibSmall moleculeModerate. At least one finished study in people, and at least 100 people who took it. 1 completed trial, 309 people given it.

    309 people given it1 trial

    • Ruxolitinib worked in a blood cancer, and that is the only thing this trial shows. Just over three hundred people with a serious bone marrow disease got either the drug or a dummy pill, and nobody involved knew which. Spleens shrank sharply in four in ten on the drug, against almost nobody on the dummy. Symptoms eased for nearly half. Fewer people died on the drug. Low red cells and low platelets were common. Both cases that turned into leukaemia were on the drug.

      The numbers COMFORT-I, NCT00952289, 309 patients with intermediate-2 or high-risk myelofibrosis. Spleen volume reduction of at least 35 percent at 24 weeks: 41.9 percent on ruxolitinib against 0.7 percent on placebo. Total symptom score improved by at least 50 percent in 45.9 percent against 5.3 percent. Thirteen deaths on ruxolitinib against 24 on placebo (hazard ratio 0.50, 95 percent CI 0.25 to 0.98). Anaemia and thrombocytopenia were the commonest adverse events; both transformations to acute myeloid leukaemia were in the ruxolitinib arm. This is a cancer trial, not an ageing trial.

      New England Journal of Medicine, 2012· 309 people

15. 15Sodium phenylbutyrateSmall moleculeModerate. At least one finished study in people, and at least 100 people who took it. 2 completed trials, 148 people given it.4 reported

    137 people given it1 trial

    • In ALS, a pill combining sodium phenylbutyrate with a bile acid slowed the loss of daily function a little over six months, compared with a dummy pill. 137 people took part. The other measures of strength, breathing and survival did not differ. This small trial led to an approval that was pulled after a larger trial failed.

      The numbers 137 people with definite ALS randomised 2:1 double-blind to sodium phenylbutyrate 3 g plus taurursodiol 1 g, or placebo, for 24 weeks (CENTAUR). ALSFRS-R declined 1.24 versus 1.66 points per month (difference 0.42, 95% CI 0.03 to 0.81, p=0.03). The secondary outcomes (muscle strength, neurofilament, slow vital capacity, survival composites) did not separate from placebo. Adverse events were mainly gastrointestinal.

      The New England Journal of Medicine, 2020· 137 people

    Also measured in animals or in the lab

    • found nothingIn mice. In the NIA mouse lifespan program, 4-phenylbutyrate did not clearly make either sex live longer at the dose and method used.

      The numbers Interventions Testing Program. 4-phenylbutyrate did not increase lifespan significantly at the dose and method of administration tested, in either sex.

      GeroScience, 2024· animal study

16. 16LandogrozumabBiologicModerate. At least one finished study in people, and at least 100 people who took it. 3 completed trials, 726 people given it.

    125 people given it1 trial

    • In people with pancreatic cancer, the antibody did not help and the treated groups did worse. 125 patients on chemotherapy were split by chance between two doses of the drug and a dummy injection. Those on the dummy lived about ten and a half months. On the lower dose it was just under ten months, and on the higher dose about eight. Tumour shrinkage and time before the cancer grew again also favoured the dummy. Wasting from cancer is not the wasting of old age.

      The numbers 125 participants with pancreatic cancer on chemotherapy, randomised to LY2495655 at 100 mg, 300 mg or placebo (NCT01505530, results posted 2018). Every measure favoured placebo. Median overall survival 10.45 months on placebo against 9.82 at 100 mg and 8.02 at 300 mg. Progression free survival 8.21 against 6.87 and 4.90 months. Response rate 26.8 percent against 25.6 and 22.0 percent. The treated arms did worse. Wasting from cancer is a different mechanism from disuse or ageing, and this is the population where the idea failed hardest.

      ClinicalTrials.gov, 2015· 125 people

17. 17Efimosfermin alfaBiologicModerate. At least one finished study in people, and at least 100 people who took it. 2 completed trials, 186 people given it.2 reported

    102 people given it1 trial

    • Liver fat fell sharply. 102 people with fatty liver disease got efimosfermin or a dummy shot for 12 weeks. By week 12, 89 percent of those on the drug had cut their liver fat by at least 30 percent, against 7 percent on the dummy. Side effects were mostly mild nausea and diarrhoea. Liver fat on a scan is not scarring on a biopsy, and 12 weeks is short. Boston Pharmaceuticals paid for the study.

      The numbers 102 participants, 12 weeks, phase 2a with safety and tolerability as the stated primary measure and efficacy only as exploratory biomarkers. At week 12, 47 of 53 evaluable participants on efimosfermin (89 percent) had at least a 30 percent reduction in liver fat fraction against 2 of 30 (7 percent) on placebo. Gastrointestinal events were the commonest adverse event, 40 percent against 24 percent, with no treatment related deaths. Funded by Boston Pharmaceuticals.

      The Lancet Gastroenterology and Hepatology, 2025· 102 people

18. 18NavitoclaxSmall moleculeModerate. At least one finished study in people, and at least 100 people who took it. 2 completed trials, 137 people given it.2 reported

    46 people given it1 trial

    • Navitoclax on its own barely touched advanced ovarian cancer. 46 women whose cancer no longer responded to chemo took it, with no comparison group, after a median of four earlier treatments. One woman's tumour shrank. 15 saw theirs hold steady. Half were back to growing cancer within about seven weeks. In 12 of the 46, platelets dropped to dangerous levels, which forced a dose cut in 8 and stopped treatment in 3. The authors called the results poor.

      The numbers 46 women with platinum-resistant high-grade serous ovarian cancer, median four prior lines, single-arm. Three-month progression-free survival 22.7 percent, median progression-free survival 1.64 months, one partial response and 15 stable diseases. Grade 3 or 4 thrombocytopenia in 12 of 46, causing dose reduction in 8 and discontinuation in 3. The authors concluded activity was poor.

      Gynecologic Oncology, 2022· 46 people

19. 19NomlabofuspBiologicLimited. People have taken it in a published study, but fewer than 100 of them. 2 completed trials, 28 people given it.

    28 people given it1 trial

    • The drug got the missing protein into the body, which is not the same as helping anyone. Fifty five adults with Friedreich ataxia took part across two short safety studies, some getting one shot and some getting daily shots for under two weeks. Nobody involved knew who got the real thing. Side effects were mostly mild and nobody was seriously harmed. Levels of the protein rose in skin, cheek cells and platelets. No symptom or daily ability was measured. The maker paid and most authors work there.

      The numbers Two double blind placebo controlled phase 1 trials in adults aged 19 to 69 with Friedreich ataxia: single ascending dose 25 to 100 mg (28 participants) and multiple ascending dose up to 100 mg daily for 13 days (27 participants). Mostly mild adverse events, no serious adverse events or deaths; peak plasma levels at 15 minutes; frataxin rose in buccal cells, skin and platelets with higher and more frequent dosing. Funded by Larimar Therapeutics; most authors are or were Larimar employees.

      Annals of Clinical and Translational Neurology, 2024· 28 people

20. 20RapamycinSmall moleculeLimited. People have taken it in a published study, but fewer than 100 of them. 2 completed trials, 25 people given it.8 reported

    25 people given it1 trial

    • The first safety look at rapamycin itself in fairly healthy older adults was small. 25 people aged 70 to 95 took 1 mg a day or a dummy pill. 11 on rapamycin and 14 on the dummy finished at least 8 weeks. The study was built to see if they could take it, not to see if they aged slower. Face rash and mouth sores showed up. Do not read a lifespan claim into it.

      The numbers Placebo-controlled pilot in 25 generally healthy adults aged 70 to 95, randomised to rapamycin 1 mg daily or placebo. 11 on rapamycin and 14 controls completed at least 8 weeks and were analysed. The trial found the dose was safe enough to continue. It did not test lifespan.

      Experimental Gerontology, 2018· 25 people

    Also measured in animals or in the lab

    • In mice: started at 600 days old, which is late in life, rapamycin made mice live longer at three separate labs. Among the longest lived, females gained 14 percent and males 9 percent.

      The numbers Started at 600 days of age, rapamycin extended lifespan at three sites: 14% in females and 9% in males at the 90th percentile.

      Nature, 2009· animal study

21. 21DT2216Small moleculeLimited. People have taken it in a published study, but fewer than 100 of them. 1 completed trial, 20 people given it.3 reported

    20 people given it1 trial

    • DT2216 was built to spare platelets, and in its first study in people it mostly did. 20 adults with advanced solid cancers got it through a drip twice a week, at rising doses. Only one person hit a dose-limiting problem, a severe platelet drop that cleared within two days. Cancer held steady in 20 percent of patients. Half were alive at about eight months. This was a safety and dosing study, not a test of whether it helps. The US National Institutes of Health supported it.

      The numbers 20 patients, median age 60.5, 60 percent female, dose escalation 0.04 to 0.4 mg/kg intravenously twice weekly. One dose-limiting toxicity, a grade 4 thrombocytopenia resolving within 48 hours; lowest first-cycle platelet count 24,000 to 297,000, recovery above 50,000 within four days in all cases. Stable disease in 20 percent, median overall survival 7.9 months. Recommended phase 2 dose 0.4 mg/kg. National Institutes of Health supported.

      Journal of Hematology and Oncology, 2025· 20 peoplepoints the wrong way

22. 22OrforglipronSmall moleculeStrong. At least two finished studies in people, and at least 1,000 people who took it. 8 completed trials, 17,383 people given it.8 reported

    nobody was given it1 watch-only study

    • A pill in this drug class produced real weight loss in people with both obesity and type 2 diabetes. 1,613 adults took one of three doses or a dummy pill for about seventeen months. Weight fell by roughly 5, 7 and 10 percent as the dose rose, against about 2 percent on the dummy. More people quit for side effects on the drug. Ten people died, six on drug and four on dummy, judged unrelated. Eli Lilly funded it, and some authors are employees who hold its stock.

      The numbers 1,613 adults with obesity and type 2 diabetes across 136 sites in ten countries, 72 weeks. Weight change by the treatment-regimen estimand was -5.1, -7.0 and -9.6 percent on 6, 12 and 36 mg against -2.5 percent on placebo, all p<0.0001. Discontinuation for adverse events 6.1 to 9.9 percent against 4.1 percent. Ten deaths, six on drug and four on placebo, all judged unrelated except one placebo case and one 12 mg case for which no treatment-related association was reported. Funded by Eli Lilly, with employee-shareholder authors.

      The Lancet, 2026· 1,613 peopleobserved only, nobody was given it

23. 23GDF15BiologicModerate. At least one finished study in people, and at least 100 people who took it. 2 completed trials, 313 people given it.3 reported

    nobody was given it1 watch-only study

    • Higher GDF15 marked out men who died sooner, but nobody was given anything. 876 Swedish men aged 35 to 80 gave a blood sample and were then followed for up to 14 years. Those with more GDF15 at the start were roughly three times as likely to die of any cause. The pattern held in a separate set of 324 twins. This is a group watched over time, not a trial. It cannot tell you whether lowering GDF15 would help anyone.

      The numbers 876 Swedish men aged 35 to 80 followed up to 14 years: serum GDF15 at entry predicted all-cause mortality with an adjusted odds ratio of 3.38 (95 percent CI 1.38 to 8.26), validated in 324 same-sex twins and independent of telomere length, IL-6 and CRP. An association in a cohort, not an intervention.

      Aging Cell, 2010· 876 peopleobserved only, nobody was given it

24. 24AdiponectinBiologicPreliminary. Studied in people, but no published study has had people take it. 3 human studies where nobody was given it.2 reported

    nobody was given it2 watch-only studies

    • Genetics points the harm the wrong way for anyone hoping to raise adiponectin. 356 people with type 2 diabetes in Italy were followed for about five and a half years, and 58 died of heart disease. Those carrying a gene variant that raises adiponectin died of heart disease about twice as often. The genetic signal was stronger than the plain observed one, which the authors read as evidence the paradox is real. Public money paid for it.

      The numbers Gargano Heart Study, 356 patients with type 2 diabetes, mean follow-up 5.4 years, 58 cardiovascular deaths. The ADIPOQ variant rs822354 raised adiponectin and was associated with cardiovascular mortality (incidence rate ratio 1.94, 95 percent CI 1.23 to 3.07), with a genetic effect larger than the observational one, interpreted by the authors as evidence that the paradoxical association is causal. Non-US government funded.

      Cardiovascular Diabetology, 2016· 356 peopleobserved only, nobody was given it

    • More adiponectin is not better, and above a point it goes with dying sooner. In older adults free of heart disease, the risk of death fell as adiponectin rose up to a middling level, then climbed again above it. In people who already had heart failure or an irregular heartbeat, higher adiponectin went with clearly higher death rates. Nobody was given anything. This is a group watched over time, and it undercuts the idea of raising this hormone on purpose. The NIH paid for it.

      The numbers Population-based cohort of older adults. In those free of cardiovascular disease, the association with all-cause mortality was U-shaped: hazard ratio 0.81 per SD up to 12.4 mg/L, then 1.19 per SD (95 percent CI 1.12 to 1.27) above it. No association in those with cardiovascular disease alone; in heart failure or atrial fibrillation, higher adiponectin meant higher mortality, hazard ratio 1.31 (1.15 to 1.50) after adjustment. Results were similar for high molecular weight adiponectin and cardiovascular death. NIH funded.

      Circulation, 2012· number of people not givenobserved only, nobody was given it

25. 25DanazolHormoneLimited. People have taken it in a published study, but fewer than 100 of them. 3 completed trials, 63 people given it.5 reported

    nobody was given it1 watch-only study

    • The follow-up answers the question the early stop left open. The same 26 patients were tracked for a median of 3.3 years afterwards. Once danazol stopped, the improvement in blood counts lasted a median of 1.6 years and then went. Lung capacity held steady on the drug and fell away after withdrawal. Half the group was still alive 7.7 years after enrolling, and 16 of the 26 had died by the last check, most often of infection. The benefit is real, and it does not outlast the drug.

      The numbers Long-term follow-up of the same National Institutes of Health cohort, published as a brief report ten years after the original. Median follow-up 3.3 years. After danazol was stopped, median time to loss of haematologic response was 1.6 years in 12 evaluable patients. Median event free survival 5.7 years and median overall survival from enrolment 7.7 years, with 16 of 26 patients (62 percent) dead at last follow-up, infection the commonest known cause. Lung function was stable on the drug and declined after withdrawal, and 6 of 7 who restarted responded again. The original trial was stopped early on a biomarker, and this is the durability answer that early stop left open: the benefit does not outlast the drug.

      Blood Advances, 2026· 12 peopleobserved only, nobody was given it

26. 26NattokinaseBiologicStrong. At least two finished studies in people, and at least 1,000 people who took it. 9 completed trials, 1,795 people given it.6 reported

    nobody was given it1 watch-only study

    • A 92-year-old woman taking over-the-counter nattokinase bled into her abdomen and died. She had an irregular heartbeat and was on no prescribed blood thinner and no antiplatelet drug. The doctors reporting the case warn against supplements of this kind, and nattokinase in particular, in patients like her. This is one case. It is also why the bleeding risk is not theoretical.

      The numbers Case report: a 92-year-old woman with atrial fibrillation, taking over-the-counter nattokinase and no prescribed anticoagulant or antiplatelet drug, developed spontaneous bleeding into the abdominal cavity and died. The authors warn against consumption of herbal supplements, especially nattokinase, in this kind of patient.

      Cureus, 2021· number of people not givenobserved only, nobody was given it

27. 27Alpha-2-MacroglobulinBiologicLimited. People have taken it in a published study, but fewer than 100 of them. 1 completed trial, 75 people given it.6 reported

    nobody was given it1 watch-only study

    • Nobody was given anything, and this is not an ageing study in the usual sense. Researchers compared the sugar coating on alpha-2-macroglobulin from newborn umbilical cord blood against pooled adult blood. The total sugar content was the same. The newborn version carried different charges and more branched sugar chains. That may change how quickly the body clears the protein, which could explain why newborns carry more of it. This is a laboratory comparison of two blood pools, not a test of anything.

      The numbers Human observational. Glycosylation features of alpha-2-macroglobulin vary with age. A measurement of how the protein changes across the lifespan, not a test of any intervention.

      Cell Biochemistry and Biophysics, 2019· number of people not givenobserved only, nobody was given it

Peptides and blends

1. 01TB-500PeptidePreliminary. Studied in people, but no published study has had people take it. 1 registered with no result.9 reported

   1 animal or lab study

   Measured in animals or in the lab

   • In mice after a blocked heart artery, thymosin beta-4, the parent peptide, helped heart muscle cells survive and the heart pump better. This was not TB-500.

     The numbers After coronary artery ligation in mice, thymosin beta-4 upregulated ILK/Akt, enhanced early myocyte survival and improved cardiac function.

     Nature, 2004· animal study

2. 02HumaninPeptideLimited. People have taken it in a published study, but fewer than 100 of them. 1 completed trial, 30 people given it.6 reported

   1 animal or lab study

   Measured in animals or in the lab

   • In worms, making more humanin helped them live longer. In mice, a lab-made version improved metabolic health. In people, humanin in the blood was higher in 18 grown children of people who lived to 100 than in 19 people of the same age. In spinal fluid from just 7 people, it was lower in those with Alzheimer's.

     The numbers Humanin overexpression extended lifespan in C. elegans and an analogue improved metabolic healthspan in mice. In a human Ashkenazi Jewish cohort, circulating humanin was significantly higher in the 18 adult offspring of centenarians than in 19 age-matched controls (p<.05); in a 4-person CSF sample, humanin was lower in Alzheimer's patients than 3 controls (p<.05, very small n).

     Aging (Albany NY), 2020· animal study

3. 03Thymosin Beta-4PeptideStrong. At least two finished studies in people, and at least 1,000 people who took it. 5 completed trials, 1,382 people given it.9 reported

   1 animal or lab study

   Measured in animals or in the lab

   • In mice after a blocked heart artery, thymosin beta-4 helped heart muscle cells survive and the heart work better.

     The numbers After coronary ligation in mice, Tbeta4 activated ILK/Akt, improved early cardiomyocyte survival and cardiac function.

     Nature, 2004· animal study

4. 04VilonPeptideAnimal or lab only. Only animal or lab studies on this page. No study in people yet. 1 animal study, 1 lab study, no human study.6 reported

   1 animal or lab study

   Measured in animals or in the lab

   • In mice. Vilon given from 6 months of age made female mice more active, gave them more stamina, helped them live longer and cut tumors.

     The numbers Lys-Glu from month 6 of life increased physical activity and endurance, prolonged lifespan and reduced spontaneous tumors in female CBA mice.

     Bulletin of Experimental Biology and Medicine, 2000· animal study

5. 05OvagenPeptideAnimal or lab only. Only animal or lab studies on this page. No study in people yet. 1 animal study, 1 lab study, no human study.7 reported

   1 animal or lab study

   Measured in animals or in the lab

   • In fruit flies, mice and rats, and a different product. A cow pineal gland extract helped these animals live longer on average. It is the best animal result in this whole family. We show it as the benchmark. Ovagen has nothing like it.

     The numbers The best-documented animal result in the whole bioregulator family, for a different organ preparation entirely. Mean lifespan rose 11 to 31 percent in female Drosophila, SHR mice, C3H/Sn mice and LIO rats. It is cited on this page as the class benchmark: this is what a bioregulator result looks like when one exists, and Ovagen has nothing comparable.

     Mechanisms of Ageing and Development, 1998· animal study

Supplements

1. 01FisetinSupplementLimited. People have taken it in a published study, but fewer than 100 of them. 1 completed trial, none stating how many people.3 reported

   2 animal or lab studies

   Measured in animals or in the lab

   • In mice: of 10 plant compounds tested, fisetin was the best at clearing worn-out cells. Given late in life, it made mice live longer, both on average and at the top end.

     The numbers Most potent senolytic among 10 flavonoids; late-life fisetin reduced senescence markers and extended median and maximum lifespan in mice.

     EBioMedicine, 2018· animal study

   • In mice: the US government's ageing test program gave fisetin to mice. It did not really change how long males or females lived at the doses used.

     The numbers NIA Interventions Testing Program: fisetin did not significantly affect lifespan in either sex at the doses used.

     GeroScience, 2024· animal study

2. 02Calcium AKGSupplementPreliminary. Studied in people, but no published study has had people take it. 1 human study where nobody was given it.3 reported

   2 animal or lab studies

   Measured in animals or in the lab

   • found nothingIn mice: the US government's ageing test program gave AKG to mice starting at two different ages. Neither males nor females lived longer at either age.

     The numbers NIA Interventions Testing Program: alpha-ketoglutarate did not increase lifespan in male or female mice at either starting age tested.

     GeroScience, 2026· animal study

   • In mice: calcium AKG in the food made mice live longer and spend less of their life frail. Their blood showed lower levels of swelling signals.

     The numbers Dietary calcium AKG extended lifespan and compressed frailty in C57BL/6 mice, with lower systemic inflammatory cytokines.

     Cell Metabolism, 2020· animal study

3. 03Caffeic acid phenethyl esterSupplementAnimal or lab only. Only animal or lab studies on this page. No study in people yet. 4 animal studies, 2 lab studies, no human study.1 reported

   2 animal or lab studies

   Measured in animals or in the lab

   • In mice. A second look at the NIA mouse lifespan program. CAPE at 300 ppm from 4 months: 147 treated females against 289 untreated ones. Typical female lifespan was 5 percent higher. The standard test just missed. The Gehan test, which counts early deaths more, just passed. Males showed nothing at 30 or 300 ppm. This was one of 132 comparisons, with no adjustment reported for running so many. Public NIA money paid for it.

     The numbers CAPE 300 ppm from 4 months, 147 treated females against 289 controls: median lifespan +5 percent, log-rank p = 0.0665, Gehan p = 0.0481, proportional hazards assumption not violated. No male effect at 30 or 300 ppm. One of 132 comparisons reanalysed with no multiplicity correction reported. NIA funded.

     GeroScience, 2024· animal study

   • found nothingIn mice. This NIA mouse lifespan program report tested CAPE at two doses. By the standard test, it did not clearly make male or female mice live longer. Public NIA money paid for it.

     The numbers The ITP report whose cohort tested CAPE at two doses and found no significant lifespan effect in either sex by the protocol log-rank test. NIA funded.

     Nature, 2009· animal study

4. 04Green tea extractSupplementModerate. At least one finished study in people, and at least 100 people who took it. 1 completed trial, 1,075 people given it.4 reported

   2 animal or lab studies

   Measured in animals or in the lab

   • In mice. A second look at the NIA mouse lifespan program. Green tea extract at 2,000 ppm from 4 months: 129 treated females against 275 untreated ones. Typical female lifespan rose 7 percent. The standard test said that could be chance. The Gehan test, which counts early deaths more, said it held up. Males showed nothing. This was one of 132 comparisons, with no adjustment reported for running so many. The authors say the effect is limited to midlife. Public NIA money paid for it.

     The numbers Green tea extract 2,000 ppm from 4 months, 129 treated females against 275 controls: median lifespan +7 percent, log-rank p = 0.37, Gehan p = 0.034, proportional hazards assumption violated. No male effect. One of 132 comparisons reanalysed without a reported multiplicity correction; the authors describe the effect as limited to midlife. NIA funded.

     GeroScience, 2024· animal study

   • In mice. The NIA mouse lifespan program tested five supplements, including green tea extract from 4 months. None clearly made male or female mice live longer by the standard test. A side look hinted the extract might cut midlife deaths in females only. Public NIA money paid for it.

     The numbers ITP report: none of the five agents, including green tea extract from 4 months, had a statistically significant effect on lifespan in either sex by log-rank test; a secondary analysis suggested the extract might reduce midlife deaths in females only. NIA funded.

     Journals of Gerontology Series A, 2013· animal study

5. 05NDGASupplementAnimal or lab only. Only animal or lab studies on this page. No study in people yet. 2 animal studies, no human study.4 reported

   2 animal or lab studies

   Measured in animals or in the lab

   • found nothingIn mice, the result held at three different doses, which is rare. Male mice lived longer on average at the first dose, at a dose three times lower and at one three times higher. Bigger doses did more. The longest-lived mice did not live any longer. Females got nothing.

     The numbers Interventions Testing Program. The male-specific extension of median lifespan by NDGA was replicated at the original dose and at doses threefold lower and threefold higher. Effects were dose dependent and male specific, and there was no effect on maximal lifespan. Replication across three doses in the same programme is unusual and is the strongest thing about this compound.

     Aging Cell, 2016· animal study

   • In mice, this is the first report of the male-leaning lifespan result. NDGA, acarbose and 17-alpha-estradiol all helped males more than females.

     The numbers The original report of the male-preferential lifespan effect, alongside acarbose and 17-alpha-estradiol.

     Aging Cell, 2014· animal study

6. 06AstaxanthinSupplementAnimal or lab only. Only animal or lab studies on this page. No study in people yet. 2 animal studies, no human study.5 reported

   2 animal or lab studies

   Measured in animals or in the lab

   • In mice, it helped males live longer in this round. Treatment started at 12 months old. The longest-lived males lived 6 percent longer, but that did not pass the formal test. Females on it weighed less late in life, but did not live longer. Two authors run the company that supplied the astaxanthin, and they said so.

     The numbers The positive. Astaxanthin extended lifespan in male mice, started at 12 months of age. The 90th percentile lifespan was extended in absolute value by 6 percent in males, though not significantly by the Wang-Allison test. Late-life weights were lower in females fed astaxanthin without a significant lifespan effect in them. Disclosed conflict: two authors run the company that supplies the astaxanthin used in the study.

     GeroScience, 2024· animal study

   • In mice, the retest found nothing. At a different dose or a later starting age, it did not help lifespan. In females, with all three labs added together, it was linked to shorter lives. But one lab had untreated females that lived unusually long. With that lab left out, the harm held only for two other drugs, not astaxanthin. The authors say timing and dose matter a lot.

     The numbers The retest. Astaxanthin showed no lifespan benefit when administered at a different dose or starting at a later age. In females, pooling all three sites, astaxanthin was associated with significantly reduced lifespan; site-specific reanalysis excluding one site with unusually long-lived control females left a negative effect only for mitoglitazone and pioglitazone. The authors conclude that timing and dosage are critical variables.

     GeroScience, 2026· animal study

7. 07ResveratrolSupplementModerate. At least one finished study in people, and at least 100 people who took it. 14 completed trials, 403 people given it.7 reported

   1 animal or lab study

   What people using it report

   • Not everyone in the same crowd thinks it is worth taking. Longevity doctor Peter Attia has said many times in public that he does not take resveratrol and that it has shown no meaningful human benefit. He points to the no-effect lifespan result in the US government's mouse testing program.

   Measured in animals or in the lab

   • In mice. The US government's mouse testing program, at three sites, found resveratrol did not make male or female mice live longer. The earlier good survival result was in mice on a high-calorie diet.

     The numbers The NIA Interventions Testing Program, three sites, treatment from four months of age, with Sinclair and Baur among the authors. Resveratrol had no statistically significant effect on lifespan in male or female mice at the concentrations tested. The 2006 Nature result of improved survival applied to mice on a high-calorie diet, and a 2008 paper from the same collaboration found no lifespan extension on a normal diet.

     Journals of Gerontology Series A, 2013· animal study

8. 08Nicotinamide RibosideSupplementLimited. People have taken it in a published study, but fewer than 100 of them. 4 completed trials, 90 people given it.5 reported

   1 animal or lab study

   Measured in animals or in the lab

   • found nothingIn mice: the US government's ageing test program gave NR to mice from 8 months old. Males and females did not live any longer. The researchers noted they had expected it to work.

     The numbers NIA Interventions Testing Program: nicotinamide riboside at 1000 ppm from 8 months did not increase lifespan in either sex. The authors note this came despite data suggesting it would be effective.

     Aging Cell, 2021· animal study

9. 09SpermidineSupplementModerate. At least one finished study in people, and at least 100 people who took it. 2 completed trials, 130 people given it.4 reported

   1 animal or lab study

   Measured in animals or in the lab

   • In mice, spermidine given by mouth made them live longer and kept their hearts working better. It did this by boosting clean-up inside heart cells.

     The numbers Oral spermidine extended mouse lifespan and preserved cardiac function through enhanced cardiac autophagy and mitophagy.

     Nature Medicine, 2016· animal study

10. 10TrigonellineSupplementAnimal or lab only. Only animal or lab studies on this page. No study in people yet. 1 animal study, no human study.2 reported

    1 animal or lab study

    Measured in animals or in the lab

    • Mostly in mice and worms. Old mice had better muscle function, and worms lived 17.9% longer. Separately, people with age-related muscle loss had lower blood levels. Nobody was given it.

      The numbers Better muscle function in old mice; 17.9% lifespan extension in C. elegans; low levels in human sarcopenia.

      Nature Metabolism, 2024· animal study

11. 11Procyanidin C1SupplementAnimal or lab only. Only animal or lab studies on this page. No study in people yet. 2 animal studies, no human study.2 reported

    1 animal or lab study

    Measured in animals or in the lab

    • In old mice. Long-term treatment cut worn-out cells in the eye and eased age-related decline in how the eye is built and works. Mouse only, and it did not look at lifespan.

      The numbers Naturally aged mice. Long-term procyanidin C1 treatment reduced retinal senescent cell burden and ameliorated age-related structural and functional decline in the retina, characterised by single-cell RNA sequencing. Mouse, no lifespan endpoint.

      Proceedings of the National Academy of Sciences, 2024· animal study

12. 12EpicatechinSupplementLimited. People have taken it in a published study, but fewer than 100 of them. 4 completed trials, 44 people given it.1 reported

    1 animal or lab study

    Measured in animals or in the lab

    • In mice. In the 2021 run of the NIA mouse lifespan program, epicatechin was fed from 7 months of age. The typical male lived 836 days against 794, a 5.3 percent gain. Survival to old age rose 6.2 percent. There were 141 treated males and 298 untreated ones. Females did not live longer (typical lifespan down 2.2 percent). Public NIA money paid for it.

      The numbers Interventions Testing Program 2021 cohort, treatment from 7 months. Male median lifespan 836 versus 794 days (+5.3 percent, log-rank p = 0.037), 90th percentile survival +6.2 percent (p = 0.01); 141 treated males against 298 controls. Females: median -2.2 percent, p = 0.6. NIA funded.

      GeroScience, 2026· animal study

13. 13(R/S)-1,3-ButanediolSupplementLimited. People have taken it in a published study, but fewer than 100 of them. 1 completed trial, none stating how many people.2 reported

    1 animal or lab study

    Measured in animals or in the lab

    • In mice. Mice missing a key ketone-making enzyme (HMGCS2) died early, and a 1,3-butanediol diet prevented that. In normal mice, the same diet started early in life raised midlife deaths. Started in old mice, it extended lifespan. It also prevented deaths from clogged arteries in mice bred to get them (ApoE-deficient). A keto diet with no limit on food sharply raised deaths. An independent Japanese group did the work.

      The numbers Mice lacking the ketogenesis enzyme HMGCS2 died early, which a 1,3-butanediol diet prevented. In normal mice the same diet started early in life increased midlife mortality, while started in aged mice it extended lifespan and prevented atherosclerosis deaths in ApoE-deficient mice. An ad libitum ketogenic diet markedly increased mortality. Independent Japanese group.

      Aging Cell, 2023· animal study

14. 14InulinSupplementLimited. People have taken it in a published study, but fewer than 100 of them. 1 completed trial, 39 people given it.6 reported

    1 animal or lab study

    Measured in animals or in the lab

    • found nothingIn mice. A diet with 8 percent glycine made male and female mice live 4 to 6 percent longer, and raised the longest lifespans too. In the same test run, inulin, used as a source of soluble fibre, gave no benefit. Neither did the drug TM5441, or aspirin at either of two doses.

      The numbers Interventions Testing Program. An 8 percent glycine diet produced a 4 to 6 percent lifespan increase, with an increase in maximum lifespan, in both males (p equals 0.002) and females (p less than 0.001). In parallel analyses of the same cohort the authors report no benefit from TM5441, from inulin described as a source of soluble fibre, or from aspirin at either of two doses.

      Aging Cell, 2019· animal study

15. 15L-leucineSupplementLimited. People have taken it in a published study, but fewer than 100 of them. 1 completed trial, 30 people given it.3 reported

    1 animal or lab study

    Measured in animals or in the lab

    • In mice. This 2017 test run tried several treatments. Rapamycin plus acarbose, started at 9 months, made male mice live longer than either drug alone had before. Captopril made female mice live 4 to 5 percent longer. The authors say the other four, including leucine, gave no lifespan benefit.

      The numbers Interventions Testing Program C2017 cohort, testing (R/S)-1,3-butanediol, captopril, leucine, the Nrf2-activating botanical mixture PB125, sulindac, syringaresinol, and rapamycin plus acarbose started at 9 or 16 months. The rapamycin and acarbose combination started at 9 months produced longer male lifespan than either drug alone in prior cohorts. Captopril gave a small 4 to 5 percent female increase. The authors state that none of the other four tested agents, which includes leucine, led to any lifespan benefit.

      Aging Cell, 2022· animal study

16. 16OxaloacetateSupplementModerate. At least one finished study in people, and at least 100 people who took it. 2 completed trials, 112 people given it.4 reported

    1 animal or lab study

    Measured in animals or in the lab

    • In mice. Five supplements were mixed into the food from 4 months of age, at three labs: resveratrol, green tea extract, curcumin, oxaloacetic acid and MCT oil. None of them changed how long male or female mice lived. A side analysis hinted that green tea extract might lower midlife deaths in females only.

      The numbers Interventions Testing Program, three test sites, treatment beginning at 4 months of age. None of the five agents, oxaloacetic acid included, had a statistically significant effect on lifespan of male or female mice by log-rank test at the concentrations tested. A secondary analysis suggested green tea extract might diminish the risk of midlife deaths in females only.

      Journals of Gerontology Series A, 2013· animal study

17. 17Ursolic acidSupplementLimited. People have taken it in a published study, but fewer than 100 of them. 1 completed trial, 16 people given it.6 reported

    1 animal or lab study

    Measured in animals or in the lab

    • In mice. Acarbose at three doses made both sexes live longer. The two higher doses made males live 16 to 17 percent longer, and females 4 to 5 percent longer. Three other treatments were tested in the same report: ursolic acid, 2-(2-hydroxyphenyl) benzothiazole and INT-767. None of them changed lifespan at the doses tested.

      The numbers Interventions Testing Program. Acarbose at 400, 1,000 and 2,500 ppm produced significant survival changes in both sexes, with the two higher doses giving 16 to 17 percent increases in male median longevity against 4 to 5 percent in females. In the same report, three other interventions were tested, ursolic acid, 2-(2-hydroxyphenyl) benzothiazole and INT-767, and none of these affected lifespan at the doses tested.

      Aging Cell, 2019· animal study

18. 18MCT oilSupplementModerate. At least one finished study in people, and at least 100 people who took it. 1 completed trial, 152 people given it.6 reported

    1 animal or lab study

    Measured in animals or in the lab

    • In mice. Five supplements were mixed into the food from 4 months of age, at three labs: resveratrol, green tea extract, curcumin, oxaloacetic acid and MCT oil. None of them changed how long male or female mice lived.

      The numbers Interventions Testing Program, three test sites, treatment beginning at 4 months of age. None of the five agents, medium-chain triglyceride oil included, had a statistically significant effect on lifespan of male or female mice by log-rank test at the concentrations tested.

      Journals of Gerontology Series A, 2013· animal study

19. 19ForskolinSupplementLimited. People have taken it in a published study, but fewer than 100 of them. 2 completed trials, 53 people given it.5 reported

    1 animal or lab study

    Measured in animals or in the lab

    • In mice. Six compounds were mixed into food from 7 months of age. In males, epicatechin made mice live about 5 percent longer, and halofuginone and mitoglitazone about 9 percent each. Forskolin was not one of the ones that worked. The authors note that, as before, the wins were mostly in males.

      The numbers Interventions Testing Program, mice bred in 2021, all agents fed in the diet from 7 months of age. The cohort tested 2BAct, dichloroacetate, epicatechin, forskolin, halofuginone and mitoglitazone. In males, epicatechin increased median lifespan by about 5 percent and halofuginone and mitoglitazone by about 9 percent each, with epicatechin and halofuginone also increasing 90 percent survival. Forskolin was not among the agents reported to extend lifespan. The authors note the report continues the strong male bias among the programme's positive findings.

      GeroScience, 2026· animal study

20. 20PterostilbeneSupplementLimited. People have taken it in a published study, but fewer than 100 of them. 1 completed trial, 80 people given it.4 reported

    1 animal or lab study

    Measured in animals or in the lab

    • In old rats. Rats aged 19 months ate food with a little pterostilbene added. It was picked as the best of seven similar compounds in a cell test. It reversed problems with thinking and with release of the brain chemical dopamine. Rats with more of it in a memory area of the brain had better working memory. This is about thinking in old rats, not about lifespan, and not about people.

      The numbers 19 month old Fischer 344 rats fed diets containing 0.004 or 0.016 percent pterostilbene, selected as the most effective of seven stilbenes in a cell screen. Pterostilbene reversed cognitive behavioural deficits and dopamine release deficits, and working memory correlated with pterostilbene levels in the hippocampus. Aged rats, not people, and a cognition endpoint rather than a lifespan one.

      Journal of Agricultural and Food Chemistry, 2008· animal study

21. 21NicotinamideSupplementModerate. At least one finished study in people, and at least 100 people who took it. 4 completed trials, 591 people given it.2 reported

    1 animal or lab study

    Measured in animals or in the lab

    • In a dish and in yeast. At normal body levels, nicotinamide blocked the yeast sirtuin and the human sirtuin SIRT1, about as well as the best man-made blockers. In yeast, it switched off gene silencing and cut lifespan to that of yeast with no sirtuin. Nobody has shown this happens in a person taking a supplement, or that it does not.

      The numbers Purified enzyme and yeast work. Physiological concentrations of nicotinamide non-competitively inhibited both yeast Sir2 and human SIRT1 in vitro, with an IC50 below 50 micromolar, which the authors describe as equal to or better than the best synthetic inhibitors of the class. In yeast, nicotinamide abolished silencing, increased rDNA recombination and shortened replicative lifespan to that of a sir2 mutant. This is yeast and test-tube data. It has never been shown to occur in a person taking a supplement, and it has never been shown not to.

      Journal of Biological Chemistry, 2002· lab (cells in a dish)

22. 22NRPTSupplementModerate. At least one finished study in people, and at least 100 people who took it. 3 completed trials, 176 people given it.3 reported

    1 animal or lab study

    Measured in animals or in the lab

    • found nothingIn mice. In the US government mouse testing program, mixed-breed mice fed nicotinamide riboside from 8 months old did not live longer, male or female, across three labs. In the same group, a drug called 17-alpha-estradiol made males live 19 percent longer on average. That shows the test could spot a big effect.

      The numbers The relevant lifespan null for the nicotinamide riboside half of this product. In the National Institute on Aging Interventions Testing Program, genetically heterogeneous UM-HET3 mice fed nicotinamide riboside from 8 months of age showed no significant effect on lifespan in either sex in the pooled three-site dataset, the programme's primary endpoint. In the same cohort and the same three sites, 17-alpha-estradiol extended median male lifespan by 19 percent, demonstrating the experiment could detect a large effect. Funded by the National Institute on Aging, conflicts declared as none.

      Aging Cell, 2021· animal study

23. 23CurcuminSupplementModerate. At least one finished study in people, and at least 100 people who took it. 3 completed trials, 195 people given it.5 reported

    1 animal or lab study

    Measured in animals or in the lab

    • In mice. The US National Institute on Aging fed curcumin to mice for life, starting at 4 months old. It did not make male or female mice live longer at the dose tested.

      The numbers NIA Interventions Testing Program. Lifelong curcumin from 4 months of age did not extend lifespan in male or female genetically heterogeneous mice at the concentration tested.

      Journals of Gerontology Series A, 2013· animal study

Other compounds

1. 01KlothoBiologicPreliminary. Studied in people, but no published study has had people take it. 2 human studies where nobody was given it.

   2 animal or lab studies

   Measured in animals or in the lab

   • In mice: mice with extra klotho lived about 20 to 30 percent longer.

     The numbers Overexpression extended lifespan by about 20 to 30%.

     Science, 2005· animal study

   • In mice: one dose of a klotho gene therapy made males live 19.7 percent longer, with benefits to bone, muscle and brain.

     The numbers 19.7% lifespan extension in males with bone, muscle and brain benefits.

     Molecular Therapy, 2025· animal study

2. 02OSK Partial ReprogrammingBiologicPreliminary. Studied in people, but no published study has had people take it. 1 registered with no result.5 reported

   2 animal or lab studies

   Measured in animals or in the lab

   • In normally ageing mice, not ones bred to age fast, long stretches of partial reprogramming changed the kidney and skin. The longer the treatment ran, the bigger the change. Ageing clocks read younger. Genes for inflammation, worn-out cells and stress were turned down. The authors did not claim these mice lived longer.

     The numbers Mouse, physiologically ageing wild-type rather than progeroid. Long-term partial reprogramming regimens produced duration-dependent effects in kidney and skin, with reversion of epigenetic clock measures and reduced inflammation, senescence and stress-response gene expression. The authors make no lifespan extension claim for wild-type mice.

     Nature Aging, 2022· animal study

   • In mice, a virus carrying a switchable OSK system was given to very old males, 124 weeks old, through the body rather than into one organ. Their remaining life was about twice as long as untreated males, and they scored better on frailty. Read that carefully. It is remaining life from very late in life, in males only, from one lab, in a specialist journal. No independent lab and no government testing program has repeated it.

     The numbers Mouse. Systemically delivered AAV encoding an inducible OSK system, given to 124-week-old male mice, extended median remaining lifespan by 109 percent over wild-type controls and improved frailty scores. Read the number carefully: this is remaining lifespan from very late life in male mice only, from one group, in a specialty journal, and it has not been replicated by the NIA Interventions Testing Program or any independent laboratory.

     Cellular Reprogramming, 2024· animal study

3. 03OSKM Cyclic Partial ReprogrammingBiologicAnimal or lab only. Only animal or lab studies on this page. No study in people yet. 6 animal studies, no human study.5 reported

   2 animal or lab studies

   Measured in animals or in the lab

   • In mice bred to age too fast, short repeated bursts of all four Yamanaka genes improved signs of ageing in their cells and bodies, and they lived longer. In older normal mice, the same treatment helped them recover from metabolic disease and muscle injury. The paper made no claim that the normal mice lived longer.

     The numbers Mouse. In a PROGEROID model of premature ageing, short-term cyclic expression of Oct4, Sox2, Klf4 and c-Myc ameliorated cellular and physiological hallmarks of ageing and prolonged lifespan. In older WILD-TYPE mice the same treatment improved recovery from metabolic disease and muscle injury, with no lifespan claim made for those animals.

     Cell, 2016· animal study

   • In mice, the authors name the gap head on. Partial reprogramming makes mice bred to age too fast live longer, but nobody knew what longer stretches of it would do in normally ageing mice. Their answer is that cells and tissues looked younger and the method was tolerated. They did not measure lifespan.

     The numbers Mouse. The authors open by naming the gap directly: partial reprogramming extends the lifespan of a premature ageing mouse model, but the effects of longer-term partial reprogramming in physiologically ageing wild-type mice were unknown. Their result is molecular and tissue-level rejuvenation plus protocol safety, not lifespan.

     Nature Aging, 2022· animal study

4. 0417-DMAGSmall moleculeLimited. People have taken it in a published study, but fewer than 100 of them. 2 completed trials, 49 people given it.3 reported

   2 animal or lab studies

   Measured in animals or in the lab

   • In mice. A second look at the NIA mouse lifespan program. 17-DMAG at 30 ppm from 6 months: 152 treated males against 264 untreated ones. Typical male lifespan rose 7 percent. The standard test said that could be chance. The Gehan test, which counts early deaths more, said it held up. Females showed nothing. The effect on deaths seemed to fade at older ages. This was one of 132 comparisons, with no adjustment reported for running so many. Public NIA money paid for it.

     The numbers 17-DMAG 30 ppm from 6 months, 152 treated males against 264 controls: median +7 percent, log-rank p = 0.12, Gehan p = 0.032, proportional hazards assumption not violated. No female effect. Effect on mortality appears diminished at later ages. One of 132 comparisons reanalysed with no multiplicity correction reported. NIA funded.

     GeroScience, 2024· animal study

   • In a dish and in fast-ageing mice. Researchers screened drugs on worn-out skin cells from mice missing a DNA repair gene (Ercc1). HSP90 blockers cleared worn-out mouse and human cells. In those fast-ageing mice, 17-DMAG kept them healthier for longer, delayed several signs of ageing and lowered p16, a marker of worn-out cells. These mice model fast ageing, not normal ageing, and nobody measured lifespan.

     The numbers Screen of autophagy-regulating compounds in senescent Ercc1-deficient mouse fibroblasts identified HSP90 inhibitors as senolytic in mouse and human cells. In Ercc1-deficient progeroid mice, 17-DMAG extended healthspan, delayed onset of several age-related symptoms and reduced p16INK4a expression. Progeroid model, not normal ageing; no lifespan endpoint.

     Nature Communications, 2017· animal study

5. 05Metformin plus rapamycinSmall moleculePreliminary. Studied in people, but no published study has had people take it. 2 registered with no result.2 reported

   2 animal or lab studies

   Measured in animals or in the lab

   • In mice. The mouse program's own later summary says the metformin plus rapamycin survival results "were not significantly higher than those noted in earlier experiments using the same dose (14.7 ppm) of rapamycin by itself". It also reports that rapamycin at 42 ppm, started at 20 months, extended lifespan in both sexes. Public NIA money paid for it.

     The numbers The ITP's own later summary: the metformin plus rapamycin survival results "were not significantly higher than those noted in earlier experiments using the same dose (14.7 ppm) of rapamycin by itself". Also reports rapamycin at 42 ppm from 20 months extending lifespan in both sexes. NIA funded.

     Aging Cell, 2020· animal study

   • In mice. Rapamycin alone at 42 ppm made typical lifespan 23 percent longer in males and 26 percent longer in females. The oldest mice lived longer too, in both sexes. Females gained more at every dose. This shows rapamycin alone can match the pair's 23 percent when its dose is tripled. Public NIA money paid for it.

     The numbers Rapamycin alone at 42 ppm extended median lifespan 23 percent in males and 26 percent in females, with maximal lifespan increased in both sexes, and females gained more at every dose. The benchmark showing rapamycin alone can match the combination's 23 percent when its dose is tripled. NIA funded.

     Aging Cell, 2014· animal study

6. 0617-alpha-estradiolHormoneAnimal or lab only. Only animal or lab studies on this page. No study in people yet. 4 animal studies, no human study.4 reported

   2 animal or lab studies

   Measured in animals or in the lab

   • In mice, a higher dose worked even better, but still only in males. At three times the earlier dose, male mice lived longer on average, and the longest-lived ones lived longer too. The same paper found NDGA and Protandim also helped male mice. Fish oil, a bile acid drug and metformin on its own did not help. Metformin plus rapamycin did.

     The numbers Interventions Testing Program. 17-alpha-estradiol at a threefold higher dose than previously tested robustly extended both median and maximal lifespan, still only in males. The same paper reports nordihydroguaiaretic acid replicated in males at the original dose and at threefold lower and higher doses, dose-dependently and without an effect on maximal lifespan, and that Protandim extended median lifespan in males only. It also reports that neither fish oil nor ursodeoxycholic acid extended lifespan, and that metformin alone at 0.1 percent of diet did not significantly extend lifespan while metformin combined with rapamycin robustly did.

     Aging Cell, 2016· animal study

   • found nothingIn mice, it worked even when started late in life, in males. That is rare for any lifespan treatment. The same round found that nicotinamide riboside, an NAD booster people take, and three other compounds did not change lifespan in either sex.

     The numbers The late-start result, which is the property that makes this compound unusual: benefit when treatment began late in life, in males. The same cohort reports that nicotinamide riboside and three other compounds did not affect lifespan in either sex, which is the relevant null for anyone taking an NAD precursor.

     Aging Cell, 2021· animal study

7. 07MeclizineSmall moleculeAnimal or lab only. Only animal or lab studies on this page. No study in people yet. 2 animal studies, no human study.6 reported

   2 animal or lab studies

   Measured in animals or in the lab

   • In mice, it helped males live longer in this round. The mice ate it in their food from 12 months old. The longest-lived males lived 6 percent longer, but that did not pass the formal test. Treated females weighed less late in life but did not live longer.

     The numbers Interventions Testing Program. Meclizine, fed at 544 plus or minus 48 ppm and started at 12 months of age, extended lifespan in male mice. The 90th percentile lifespan was extended in absolute value by 6 percent in males but not significantly by the Wang-Allison test. Late-life weights were lower in treated females without a significant lifespan effect in them.

     GeroScience, 2024· animal study

   • In mice, the retest found nothing. At a different dose or a later starting age, it did not help lifespan. It was one of eleven compounds tested in that round. None of them made mice of either sex live longer.

     The numbers The retest. Meclizine showed no lifespan benefit at a different dose or a later starting age. One of eleven compounds in that cohort, none of which increased lifespan in either sex.

     GeroScience, 2026· animal study

8. 08RilmenidineSmall moleculePreliminary. Studied in people, but no published study has had people take it. 1 human study where nobody was given it.1 reported

   2 animal or lab studies

   Measured in animals or in the lab

   • In worms. Rilmenidine made tiny worms live longer and handle stress better, whether they started young or old. It only worked through one specific receptor and the cell's clean-up system. It added nothing for worms already eating less or on rapamycin. In mice, it changed genes in the liver and kidney to look like eating less, but the mice's lifespan was not measured. Two authors have business interests in longevity.

     The numbers The paper that put rilmenidine into geroscience. Identified by searching for compounds with a caloric-restriction-like expression signature. Increased lifespan in C. elegans when given at young and older ages, with the stress resilience, healthspan and lifespan benefits all dependent on the I1-imidazoline receptor nish-1, on DAF-16 and SKN-1, and on autophagy but not AMPK. Adding it to calorically restricted worms, reduced TORC1 function or rapamycin produced no further gain. Mice treated with rilmenidine showed caloric-restriction-like transcriptional changes in liver and kidney, which is a gene expression finding and not a lifespan finding. Two authors disclose commercial longevity interests.

     Aging Cell, 2023· animal study

   • In mice. In a second mouse model of the same kind of nerve disease, rilmenidine again switched on cell clean-up. This time the mice died sooner and lost nerve cells faster. A key protein was also pulled out of the cell centre. This is a lifespan result pointing the wrong way.

     The numbers The second and harder negative. In TDP-43WTxQ331K double transgenic mice, rilmenidine induced robust spinal cord autophagy and exacerbated the phenotype: truncated lifespan, accelerated motor neuron loss and pronounced clearance of TDP-43 from nuclei. A lifespan result in mice pointing the wrong way.

     Neurobiology of Disease, 2021· animal study

9. 09LamivudineSmall moleculeLimited. People have taken it in a published study, but fewer than 100 of them. 1 completed trial, none stating how many people.3 reported

   2 animal or lab studies

   Measured in animals or in the lab

   • In mice and in a dish. This is the paper that started the idea. In worn-out cells, jumping genes woke up and set off an immune alarm through loose DNA copies. Drugs that block the copying stopped it. Giving lamivudine to old mice turned down the alarm and cut inflammation in several body parts. It measured inflammation, not lifespan. The paper has a published author correction, which is not a retraction.

     The numbers The founding paper. LINE-1 elements become transcriptionally derepressed during cellular senescence and activate a type I interferon response, triggered by cytoplasmic LINE-1 complementary DNA and blocked by LINE-1 reverse transcriptase inhibitors. Treating aged mice with lamivudine downregulated interferon activation and age-associated inflammation in several tissues. Inflammation endpoints, not survival. The paper carries a published author correction in Nature in 2019, which is a correction and not a retraction.

     Nature, 2019· animal study

   • In mice. Mice missing the SIRT6 gene age fast and die young. They build up loose jumping-gene DNA that sets off an immune alarm. Drugs like lamivudine made these mice healthier, helped them live longer, and fully switched off the alarm. Normal old mice showed the same alarm signs, but nobody tested whether the drug helped them live longer.

     The numbers The lifespan-shaped result, and it is in a progeroid model. SIRT6-deficient mice, which are severely short lived, accumulate cytoplasmic LINE-1 complementary DNA that triggers a type I interferon response via cGAS. Nucleoside reverse transcriptase inhibitors significantly improved the health and lifespan of these knockout mice and completely rescued the interferon response. The same paper reports elevated LINE-1 transcription, cytoplasmic complementary DNA and type I interferon in normally aged wild-type mice, without a lifespan experiment in those animals.

     Cell Metabolism, 2019· animal study

10. 10Senolytic vaccine (anti-GPNMB)BiologicAnimal or lab only. Only animal or lab studies on this page. No study in people yet. 3 animal studies, no human study.

    2 animal or lab studies

    Measured in animals or in the lab

    • In mice. The team found GPNMB on zombie cells. Removing cells that carried it eased fat and blood sugar problems in mice on a high-fat diet and cut artery clogging. A vaccine against it cut those cells and helped male mice bred to age too fast live longer.

      The numbers Mouse. Identified GPNMB as a seno-antigen enriched in senescent cells. Genetic ablation of Gpnmb-positive cells attenuated adipose senescence and improved systemic metabolic abnormalities in high-fat-diet mice and reduced atherosclerotic burden in ApoE knockout mice. Immunisation against Gpnmb reduced Gpnmb-positive cells, improved age-related phenotypes, and extended the male lifespan of progeroid mice.

      Nature Aging, 2021· animal study

    • In human blood vessel cells in a dish and in mice. The same team found that GPNMB helps zombie cells survive. Removing it made human cells wear out sooner and made blood vessel disease in mice worse. Adding more of it protected against stress. So GPNMB is not just a harmless tag.

      The numbers The same group's mechanistic follow-up, in human endothelial cells and mice. Depleting GPNMB shortened the replicative lifespan of human vascular endothelial cells, and depleting Gpnmb in mice impaired vascular function and enhanced atherogenesis, while overexpression protected against stress-induced senescence and attenuated vascular dysfunction. GPNMB is a survival factor maintaining lysosomal integrity in senescent cells, not a neutral surface tag.

      Scientific Reports, 2022· animal study

11. 11FGF21BiologicModerate. At least one finished study in people, and at least 100 people who took it. 2 completed trials, 350 people given it.4 reported

    2 animal or lab studies

    Measured in animals or in the lab

    • In mice bred to make extra FGF21. They lived much longer without eating less. It seems to work by turning down growth hormone signals in the liver. The same mice had stunted growth and bone loss. There is no human lifespan data.

      The numbers Transgenic overexpression of FGF21 markedly extended lifespan in mice without reducing food intake, apparently by blunting hepatic growth hormone and IGF-1 signalling. The same paper records that FGF21 blocks somatic growth and causes bone loss in mice. There is no human lifespan data.

      eLife, 2012· animal study

    • In obese mice. FGF21 made them live longer, and it did not need to slow growth to do it. Mice only.

      The numbers In mice with diet-induced obesity, FGF21 extended lifespan through metabolic effects that did not depend on suppressing growth. Mouse only.

      Cell Metabolism, 2025· animal study

12. 12DasatinibSmall moleculeLimited. People have taken it in a published study, but fewer than 100 of them. 3 completed trials, 74 people given it.3 reported

    1 animal or lab study

    Measured in animals or in the lab

    • In old mice: D+Q given every so often helped them move and function better. From the point treatment began, they lived about 36 percent longer.

      The numbers Intermittent D+Q in old mice improved physical function and extended remaining lifespan by about 36%.

      Nature Medicine, 2018· animal study

13. 13Chemical Reprogramming CocktailsSmall moleculeAnimal or lab only. Only animal or lab studies on this page. No study in people yet. 1 animal study, 3 lab studies, no human study.4 reported

    1 animal or lab study

    Measured in animals or in the lab

    • In aged human cells in a dish and in a tiny worm. Chemical partial reprogramming reduced DNA damage and changes to the chemical tags on DNA in aged human cells. A two-molecule combination also cut worn-out cells and oxidative stress. That combination made worms live longer and stay healthier. The lifespan result is in a worm, not a mammal.

      The numbers Aged human cells in culture plus Caenorhabditis elegans. Chemical-induced partial reprogramming improved genomic instability and epigenetic alterations in aged human cells. An optimised two-molecule combination also reduced cellular senescence and oxidative stress, and extended lifespan and healthspan in C. elegans. The lifespan result is in a nematode, not a mammal.

      EMBO Molecular Medicine, 2025· animal study

14. 14FGF17BiologicPreliminary. Studied in people, but no published study has had people take it. 1 human study where nobody was given it.4 reported

    1 animal or lab study

    Measured in animals or in the lab

    • In animals, FGF17 both kept nerve cells alive and rebuilt the insulating sheath around nerve fibres, restoring what was lost after a stroke. That pushes the finding past normal ageing and into injury.

      The numbers Animal. FGF17 acted on neuronal survival and oligodendrogenesis together to restore deficits in a stroke model, extending the oligodendrocyte finding beyond normal ageing into injury.

      Neurotherapeutics, 2026· animal study

15. 15ABT-737Small moleculePreliminary. Studied in people, but no published study has had people take it. 1 human study where nobody was given it.1 reported

    1 animal or lab study

    Measured in animals or in the lab

    • In mice. Clearing worn-out cells, with genes or a clean-up drug, or removing a type of immune cell, shrank tumours and helped mice with a type of lung cancer live longer. Worn-out immune cells were also seen in human lung tissue before cancer, but that was only an observation, not a treatment.

      The numbers Mouse. Genetic or senolytic ablation of senescent cells, or macrophage depletion, reduced tumour burden and increased survival in KRAS-driven lung cancer models. Macrophages with senescent features were also found in human pre-malignant lung lesions, an observation rather than an intervention.

      Cancer Cell, 2023· animal study

16. 16HalofuginoneSmall moleculePreliminary. Studied in people, but no published study has had people take it. 3 human studies where nobody was given it, 1 registered with no result.2 reported

    1 animal or lab study

    Measured in animals or in the lab

    • In mice. In the 2021 run of the NIA mouse lifespan program, halofuginone was fed from 7 months of age. The typical male lived 864 days against 794, an 8.8 percent gain. Survival to old age rose 6.9 percent. There were 154 treated males and 298 untreated ones. Females did not change (typical lifespan up 0.2 percent). Public NIA money paid for it.

      The numbers Interventions Testing Program 2021 cohort, treatment from 7 months. Male median lifespan 864 versus 794 days (+8.8 percent, log-rank p = 0.002), 90th percentile survival +6.9 percent (p = 0.01); 154 treated males against 298 controls. Females: median +0.2 percent, p = 0.75. NIA funded.

      GeroScience, 2026· animal study

17. 17MitoglitazoneSmall moleculeModerate. At least one finished study in people, and at least 100 people who took it. 2 completed trials, 385 people given it.1 reported

    1 animal or lab study

    Measured in animals or in the lab

    • found nothingIn mice. In the 2021 run of the NIA mouse lifespan program, mitoglitazone was fed from 7 months of age. The typical male lived 863 days against 794, an 8.7 percent gain. Survival to old age rose 2.9 percent, which could be chance. There were 149 treated males and 298 untreated ones. Treated males were heavier at 12, 18 and 24 months. Females dipped 2.3 percent at the median, not clearly. Public NIA money paid for it.

      The numbers Interventions Testing Program 2021 cohort, treatment from 7 months. Male median lifespan 863 versus 794 days (+8.7 percent, log-rank p = 0.015); 90th percentile survival +2.9 percent, not significant (p = 0.19); 149 treated males against 298 controls. Treated males were heavier at 12, 18 and 24 months. Females: median -2.3 percent, p = 0.07. NIA funded.

      GeroScience, 2026· animal study

18. 18Rapamycin plus acarboseSmall moleculeAnimal or lab only. Only animal or lab studies on this page. No study in people yet. 7 animal studies, no human study.5 reported

    1 animal or lab study

    Measured in animals or in the lab

    • In mice. Rapamycin alone, started at 600 days of age, raised survival to old age 14 percent in females and 9 percent in males across three labs. This is the first rapamycin result, and the one the pair is measured against. Public NIA money paid for it.

      The numbers Rapamycin alone from 600 days of age: 90th percentile survival +14 percent in females and +9 percent in males at three sites. The founding rapamycin result the combination is measured against. NIA funded.

      Nature, 2009· animal study

19. 19MifepristoneSmall moleculeModerate. At least one finished study in people, and at least 100 people who took it. 2 completed trials, 320 people given it.4 reported

    1 animal or lab study

    Measured in animals or in the lab

    • In mice. The NIA mouse lifespan program tested eleven compounds in mixed-breed mice at three labs. Mifepristone did not clearly make male or female mice live longer.

      The numbers Interventions Testing Program, eleven compounds in genetically heterogeneous UM-HET3 mice at three sites. Mifepristone did not significantly increase lifespan in male or female mice.

      GeroScience, 2026· animal study

20. 20MethotrexateSmall moleculeStrong. At least two finished studies in people, and at least 1,000 people who took it. 2 completed trials, 5,022 people given it.4 reported

    1 animal or lab study

    Measured in animals or in the lab

    • In mice. The NIA mouse lifespan program tested eleven compounds in mixed-breed mice at three labs. Methotrexate did not clearly make male or female mice live longer.

      The numbers Interventions Testing Program, eleven compounds in UM-HET3 mice at three sites. Methotrexate did not significantly increase lifespan in male or female mice.

      GeroScience, 2026· animal study

21. 21Dimethyl fumarateSmall moleculeLimited. People have taken it in a published study, but fewer than 100 of them. 3 completed trials, 54 people given it.4 reported

    1 animal or lab study

    Measured in animals or in the lab

    • found nothingIn mice. In the NIA mouse lifespan program, dimethyl fumarate did not clearly make either sex live longer at the dose and method used. The amount in the food averaged 35 percent of the planned dose, which the authors say may explain the lack of effect. Note the conflicts of interest: two authors run a company that supplied the astaxanthin used, and others hold patents or company stakes in drugs that clear worn-out cells.

      The numbers Interventions Testing Program. Dimethyl fumarate did not increase lifespan significantly in either sex at the dose and method of administration tested. The authors report that the amount in the diet averaged 35 percent of the target dose, which they state may explain the absence of lifespan effects. Note the disclosed conflicts in this paper: two authors run a company supplying the astaxanthin used, and others hold senolytic patents or company interests.

      GeroScience, 2024· animal study

22. 22Mycophenolic acidSmall moleculeModerate. At least one finished study in people, and at least 100 people who took it. 2 completed trials, 227 people given it.5 reported

    1 animal or lab study

    Measured in animals or in the lab

    • found nothingIn mice. In the NIA mouse lifespan program, mycophenolic acid did not clearly make either sex live longer at the dose and method used.

      The numbers Interventions Testing Program. Mycophenolic acid did not increase lifespan significantly at the dose and method of administration tested, in either sex.

      GeroScience, 2024· animal study

23. 23SG1002Small moleculeAnimal or lab only. Only animal or lab studies on this page. No study in people yet. 1 animal study, no human study.1 reported

    1 animal or lab study

    Measured in animals or in the lab

    • found nothingIn mice. In the NIA mouse lifespan program, SG1002, a hydrogen sulfide releaser, did not clearly make either sex live longer at the dose and method used.

      The numbers Interventions Testing Program. SG1002, described as a hydrogen sulfide donor, did not increase lifespan significantly at the dose and method of administration tested, in either sex.

      GeroScience, 2024· animal study

24. 24ISRIBSmall moleculeAnimal or lab only. Only animal or lab studies on this page. No study in people yet. 3 animal studies, 1 lab study, no human study.4 reported

    1 animal or lab study

    Measured in animals or in the lab

    • In mice. This is the only ageing result. In old mice, ISRIB undid memory loss for places and improved short-term memory. In the memory part of the brain, nerve cells worked more like young ones and regrew contact points. Signs of immune activity in the brain went down. It measured memory, not lifespan. Several authors have business interests in this type of drug.

      The numbers The ageing result, and the only one. ISRIB reversed integrated stress response activation in the aged mouse brain, reversed spatial memory deficits and improved working memory in old mice, and in hippocampus restored intrinsic neuronal electrophysiological properties and spine density while reducing interferon and T cell mediated immune profiles. Memory endpoints, not lifespan or healthspan. Several authors disclose commercial interests in the compound class.

      eLife, 2020· animal study

25. 25Senolytic CAR T cellsBiologicAnimal or lab only. Only animal or lab studies on this page. No study in people yet. 3 animal studies, no human study.

    1 animal or lab study

    Measured in animals or in the lab

    • In mice and in a dish. Researchers found uPAR on the surface of zombie cells and built T cells to hunt it. The cells cleared zombie cells, helped mice with lung cancer live longer, and eased liver scarring in mice. This paper was later corrected.

      The numbers Mouse and in vitro. Identified uPAR as a cell-surface protein broadly induced during senescence, and showed that uPAR-specific CAR T cells ablated senescent cells in vitro and in vivo, extended survival of mice with lung adenocarcinoma treated with a senescence-inducing drug combination, and restored tissue homeostasis in mice with chemically or diet-induced liver fibrosis. This paper carries a published Author Correction, cited below.

      Nature, 2020· animal study

26. 26o-VanillinSmall moleculeAnimal or lab only. Only animal or lab studies on this page. No study in people yet. 1 animal study, 3 lab studies, no human study.

    1 animal or lab study

    Measured in animals or in the lab

    • In human disc cells, and in whole worn human discs kept alive outside the body. o-Vanillin and a lab-made drug, RG-7112, both cut inflammatory signals. One dose helped the discs keep up their tissue, along with fewer zombie cells.

      The numbers Human cells and intact degenerating human discs maintained ex vivo. RG-7112 selectively killed senescent disc cells by apoptosis; both it and o-vanillin decreased the SASP and affected a shared cell death and survival gene network, with o-vanillin additionally affecting cell cycle and connective tissue networks. A single dose improved disc matrix homeostasis in the ex vivo discs, correlating with fewer senescent cells and less SASP.

      eLife, 2020· lab (cells in a dish)