Everolimus
Everolimus, mTOR inhibitor and rapamycin analogue
Written by Aaron CuhaReviewed Sep 2026
Also known as: RAD001, Afinitor, Zortress, Rapalog
The rapamycin analogue that produced the first credible human geroscience result: improved influenza vaccine response in older adults in a randomised trial.
Overview
Everolimus matters to this site for a reason unrelated to its approved uses. It is an approved cancer and transplant drug, and it was also the molecule used for the first randomised trial that took the mTOR longevity hypothesis into humans and got a positive answer.
That 2014 trial gave low doses to older adults and measured response to influenza vaccination, which is a reasonable proxy for immune ageing. It improved. A follow-up reported enhanced immune function and fewer infections. For a field where almost everything rests on mice, that was the strongest human signal anyone had produced.
What happened next is the important part, and it happened to a related compound rather than to this one: the properly powered phase 3 of that programme failed. Everolimus is where the human mTOR story starts, and the story does not end well.
Mechanism of action
A rapamycin analogue, or rapalog, that binds FKBP12 and inhibits mechanistic target of rapamycin complex 1. mTORC1 is the central nutrient and growth-factor sensor: when it is active, cells build protein and suppress autophagy, and when it is inhibited, autophagy and stress resistance increase. That is the same pathway dietary restriction acts through, which is the entire basis for expecting mTOR inhibition to affect ageing. Everolimus differs from rapamycin by a hydroxyethyl group that improves oral bioavailability and shortens the half-life, which is why it is easier to dose intermittently.
Human evidence
A large approved-drug record in oncology and transplantation, plus the only positive randomised human trials in geroscience, whose programme then failed at phase 3.
- Approved for multiple cancers and for transplant rejection prophylaxis, with well-characterised dosing and toxicity.
- A randomised trial in older adults found low-dose mTOR inhibition improved influenza vaccination response.
- A multicentre follow-up reported enhanced immune function and reduced infections.
- The programme's phase 3, using the related compound RTB101, did not reduce respiratory illness in 1,024 patients.
- Known risks at therapeutic oncology doses include stomatitis, immunosuppression, hyperglycaemia, hyperlipidaemia and non-infectious pneumonitis.
- No human trial has examined lifespan.
What this does not tell you: The positive trials used surrogate and short-horizon endpoints, vaccine response and self-reported infection, in modest samples. The programme's own properly powered phase 3 is the reason to hold those results loosely. Oncology doses and the low intermittent doses used in geroscience are effectively different interventions with different risk profiles, and the safety record of the former does not transfer to long-term use of the latter.
Reading the research record
Read the mTOR human programme as one sequence rather than three papers. In 2014 a randomised trial found that everolimus improved influenza vaccine response in older adults, which was the first credible human signal that inhibiting this pathway could improve an age-related function. In 2018 a follow-up reported that TORC1 inhibition enhanced immune function and reduced infections. Then in 2021 the phase 2b and phase 3 trials were published together: phase 2b reduced clinically symptomatic respiratory illness with an odds ratio whose confidence interval ran from 0.391 to 0.922 at p = 0.02, and the 1,024-person phase 3 found 26 percent against 25 percent, odds ratio 1.07, p = 0.65. Nothing. In both trials the interferon-induced antiviral genes the drug was designed to upregulate were significantly upregulated. The mechanism was confirmed and the benefit vanished, which is the single best argument on this site for distrusting biomarker endpoints.
The evidence, charted
Fig. 1 · evidence composition
3of 3 citations (100%) are in people
Every citation cited here is Human work; no other study type is cited on this page. This count is of our own citation list and understates any literature larger than the sources we cite.
Fig. 2 · evidence over time
Evidence spans 3 distinct years, 2014 to 2021, counted from the citation list on this page.
Fig. 3 · legal status at a glance
US
Approved
UK
Approved
AU
Approved
CA
Approved
Approved in all four jurisdictions shown. A jurisdiction's classification is a regulatory fact, not a verdict on the science; see Legal status below for the full text and any notes.
Fig. 4 · dose response
No human dose response curve exists
We draw this figure where the data supports it. For this compound in humans it does not, so the panel stays empty rather than borrowing an animal curve and implying it transfers.
Key studies & citations
- Human2014
mTOR inhibition improves immune function in the elderly
The first randomised human trial to take the mTOR longevity hypothesis to an age-related functional endpoint. Low-dose mTOR inhibition improved influenza vaccination response in older adults. This is the result that made human geroscience trials credible.
Science Translational Medicine - Human2018
TORC1 inhibition enhances immune function and reduces infections in the elderly
The multicentre follow-up reporting enhanced immune function and reduced infections in older adults with TORC1 inhibition. Together with the 2014 trial this is the positive half of the programme, and the phase 3 that followed is on the RTB101 page.
Science Translational Medicine - Human2021
Targeting the biology of ageing with mTOR inhibitors to improve immune function in older adults: phase 2b and phase 3 randomised trials
The end of the arc. Phase 2b was positive and the 1,024-patient phase 3 was not: 26 percent against 25 percent with clinically symptomatic respiratory illness, odds ratio 1.07, p = 0.65. Interferon-induced antiviral genes were significantly upregulated in both trials, so the mechanism held while the benefit did not.
Lancet Healthy Longevity
Frequently asked questions
Is everolimus better than rapamycin for longevity?
No trial compares them for any ageing endpoint. Everolimus has the shorter half-life, roughly 30 hours against 60 or more, which makes intermittent dosing easier and is why it was chosen for the human immune-ageing trials. Rapamycin has by far the stronger mouse lifespan record.
Did it actually improve immune function in older people?
In randomised trials, yes, on vaccine response and reported infections. The caution is that the same programme's 1,024-person phase 3 found no reduction in respiratory illness while still moving the antiviral gene expression it targeted. Treat the positive results as a signal that did not survive proper testing.
Can I take it for ageing?
It is a prescription immunosuppressant with real toxicity, including stomatitis, hyperglycaemia, raised lipids and pneumonitis, and it has no approved ageing indication. Anyone considering it needs a prescriber who will monitor for those, and should know the programme's phase 3 outcome first.