Hydralazine
Hydralazine, vasodilator and NRF2 pathway activator
Written by Aaron CuhaReviewed Sep 2026
Also known as: Apresoline, Hydralazine hydrochloride
An old blood pressure drug that extended lifespan in worms by activating the same stress pathway as dietary restriction. In mice it did nothing, in either sex.
Overview
Hydralazine is a direct vasodilator that has been used for high blood pressure since the 1950s. Its appearance in ageing research came from an unexpected direction: screens in the nematode Caenorhabditis elegans found it extended lifespan and increased stress resistance, working through the worm equivalent of the NRF2 antioxidant response pathway, which is one of the pathways dietary restriction uses.
That is a real finding in a real model organism, published in a strong journal, and it is the reason the compound was worth testing further.
The Interventions Testing Program tested it in mice and found no significant lifespan effect in either sex. The distance between a worm and a mouse is where most longevity compounds die, and this is a clean example.
Mechanism of action
Two separate mechanisms that should not be confused. Clinically it is a direct arteriolar vasodilator, reducing peripheral resistance and lowering blood pressure, with reflex tachycardia and fluid retention as consequences, which is why it is usually combined with a beta blocker and a diuretic. Its ageing rationale is unrelated: in worms it activates the NRF2 and SKN-1 signalling pathway, inducing a transcriptional stress response resembling part of the dietary restriction response. It is also a DNA methyltransferase inhibitor at higher concentrations.
Human evidence
A long approved-drug record in hypertension and heart failure, with a specific and well-known autoimmune risk. No ageing endpoints.
- Approved and used for decades for hypertension, and in combination with isosorbide dinitrate in heart failure.
- Reflex tachycardia and sodium and fluid retention are predictable consequences of direct vasodilation, which is why it is rarely used alone.
- Drug-induced lupus is a recognised risk with prolonged use, more common in slow acetylators, and it is the reason long-term unmonitored use is a poor idea.
- No human study has examined lifespan, healthspan or any geroscience endpoint.
What this does not tell you: The human record concerns blood pressure, not ageing. The longevity evidence is a worm result, and the mouse lifespan test that followed it was negative in both sexes. The drug-induced lupus risk is specific and real, which makes this one of the less sensible compounds to experiment with on the strength of invertebrate data.
Reading the research record
This is the clearest worm-to-mouse failure in the batch, and it is worth being precise about what that means. The nematode result is not junk science: it is a strong journal, a defined mechanism, and the pathway involved is genuinely one that dietary restriction uses. The problem is the translation. Nematodes are short-lived, lack most mammalian physiology, and are unusually responsive to stress-response manipulation, so lifespan extension in that model has a poor record of carrying over.
That is why the Interventions Testing Program exists, and why a null from it outweighs a positive from a simpler organism. The compound also carries a specific autoimmune risk on prolonged use, so the risk-benefit here is negative rather than merely unproven.
The Interventions Testing Program is run by the National Institute on Aging at three independent sites, The Jackson Laboratory, the University of Michigan and the University of Texas Health Science Center at San Antonio. It uses UM-HET3 mice, a genetically heterogeneous four-way cross, so a result cannot be an artefact of one inbred strain. Compounds are fed in the diet, both sexes are tested, cohorts are large enough to detect roughly a 10 percent lifespan change, and results are analysed by log-rank for median survival and by the Wang-Allison test for maximum lifespan. Its nulls are published alongside its positives. That combination of features does not exist anywhere else in ageing research, which is why a null here means considerably more than a null from a single laboratory.
The evidence, charted
Fig. 1 · evidence composition
0of 1 citation (0%) is in people
Every citation cited here is Animal 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
Every citation here was published in 2017.
Too few distinct publication years on this page to plot as a timeline. The newest citation on file is from 2017, more than five years ago; the published record may have gone quiet.
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.
Key studies & citations
- Animal2017
Hydralazine induces stress resistance and extends C. elegans lifespan by activating the NRF2/SKN-1 signalling pathway
Nematode work. Hydralazine extended lifespan and induced stress resistance through the NRF2 and SKN-1 pathway. This is the origin of the compound's longevity reputation and it is an invertebrate result.
Nature Communications
Frequently asked questions
Did hydralazine extend lifespan?
In worms, yes, through the NRF2 and SKN-1 stress response pathway. In mice, tested by the National Institute on Aging at three sites, no effect in either sex. The mouse result is the one that should govern any decision about a person.
Why did the worm result not carry over?
It usually does not. Nematodes are short-lived, lack most mammalian physiology and respond strongly to stress-response manipulation, so lifespan extension in that model has a weak translation record. This is the specific reason multi-site mammalian testing exists.
Is it safe to take for longevity?
No. It causes reflex tachycardia and fluid retention, and prolonged use carries a recognised risk of drug-induced lupus, especially in slow acetylators. There is no mammalian lifespan benefit to weigh against that.