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The Interventions Testing Program and Mouse Lifespan Studies

How the National Institute on Aging mouse program tests longevity candidates, which agents raised or did not raise lifespan, why results differ by sex, and why this is not human evidence.

Content last updated . This page has not been medically reviewed.

What this program is

The Interventions Testing Program (ITP) is a peer-reviewed program of the National Institute on Aging (NIA) designed to identify agents that extend lifespan and healthspan in mice. Testing is done in a genetically varied mouse stock called UM-HET3 at three sites: the Jackson Laboratory, the University of Michigan and the University of Texas Health Science Center at San Antonio. [1] Early program reports used genetically varied mice at three independent sites, chosen to avoid results tied to one genotype. [2]

Labels used on this page: preclinical (cells/animals only) for every mouse result, and insufficient evidence where a mouse result has no human trial behind it. Nothing here shows that any agent helps people live longer. See Aging in Mice, Worms and Humans for what transfers.

What the program has found

NIA's program page says that, since the program began, it has identified 15 agents and 2 combinations that significantly increase median lifespan in mice. The list includes acarbose, aspirin, astaxanthin, canagliflozin, captopril, epicatechin, glycine, halofuginone, meclizine, rapamycin, 17-alpha estradiol and the combinations rapamycin with acarbose and rapamycin with metformin. [3] A 2025 review said the program had tested 54 agents in more than 30,000 mice. [4]
Agent (as tested in mice)Result in the main NIA tableSource
RapamycinLonger median and maximum lifespan in both sexes[5]
AcarboseLonger lifespan, larger in males[6]
CanagliflozinLonger lifespan in males, not females[7]
Metformin aloneListed as no increase[5]
Resveratrol, curcumin, green tea extractListed as no increase[5]
Nicotinamide riboside, fisetin, alpha-ketoglutarateListed as no increase[5]

Some of these are prescription medicines (rapamycin, acarbose, canagliflozin, metformin). Their approved uses and risks are on their drug information pages, and the table gives no use guidance.

Results that are mixed or change with the analysis

  • Metformin. A reanalysis of 2004 to 2022 ITP data with a different statistical test (the Gehan test, more sensitive to deaths earlier in life) found metformin significantly increased survival in males, though the standard test had missed it. [8] So metformin is a mixed result in mice, not a clear yes or no.
  • Rapamycin plus acarbose. In males, the combination lived longer than in earlier cohorts given rapamycin alone, suggesting more benefit than either drug alone; in females it did not clearly differ from rapamycin alone. [9]
  • Agents that did not repeat. A 2026 report found astaxanthin, meclizine and mitoglitazone, which had been linked to lifespan gains earlier, showed no benefit at different doses or later starting ages, and said single-cohort findings need cautious reading. [10] Another 2026 report found three new agents (epicatechin, halofuginone, mitoglitazone) extended male lifespan only. [11]
  • Possible harm to one sex. In one report, canagliflozin started late and an estrogen-related compound each increased male lifespan but reduced female lifespan. [12]

Why sex matters so much

A 2025 review of two decades of ITP results found that most compounds that extended lifespan worked primarily or only in male mice, and that dose and starting age also differed by sex. [4] It argued this suggests aging mechanisms differ by sex. For readers, the lesson is that one average result can hide opposite effects in subgroups.

What these studies cannot tell you

  • Mice are not people. Doses are given in the mouse diet, and the program tests lifespan in a laboratory setting. Do not convert them to human amounts.
  • Lifespan in mice is not healthspan in people. Human trials of the same agents use disease outcomes or markers, as in Aging Clinical Trials: TAME and Other Human Studies.
  • The program is still testing agents, including taurine and urolithin A, so those entries are not results yet. [5]

For a plain-language rule of thumb, read Claim Check: "It Extended Lifespan in Mice, So It Works" and Longevity Research Limitations and Safety.

Frequently asked questions

What is the Interventions Testing Program?

An NIA program that tests candidate agents for effects on lifespan and healthspan in genetically varied mice at three sites. [1]

Did metformin extend lifespan in the program?

It was listed as no increase in the main table, but a reanalysis with a different statistical test found a survival gain in males. The result is mixed. [5][8]

Do ITP results apply to people?

No. They are mouse results. Whether the same agents help people live longer or healthier needs human trials.

Why do some drugs work only in male mice?

The reason is not settled; a 2025 review suggests aging mechanisms differ by sex. [4]

References
  1. National Institute on Aging (US NIH). Interventions Testing Program (ITP). Read 2026-10-22 (page updated July 9, 2026).
  2. Harrison DE et al. Rapamycin fed late in life extends lifespan in genetically heterogeneous mice. Nature 2009. PubMed 19587680. Read 2026-10-22.
  3. National Institute on Aging (US NIH). About the ITP. Read 2026-10-22.
  4. Jiang N et al. Sex as a major determinant of pro-longevity drug efficacy: a review of two decades of the NIA Interventions Testing Program. J Gerontol A 2025. PubMed 40717358. Read 2026-10-22.
  5. National Institute on Aging (US NIH). ITP Supported Interventions. Read 2026-10-22 (page updated April 13, 2026).
  6. Harrison DE et al. Acarbose, 17-alpha-estradiol, and nordihydroguaiaretic acid extend mouse lifespan preferentially in males. Aging Cell 2014. PubMed 24245565. Read 2026-10-22.
  7. Miller RA et al. Canagliflozin extends life span in genetically heterogeneous male but not female mice. JCI Insight 2020. PubMed 32990681. Read 2026-10-22.
  8. Jiang N et al. The Gehan test identifies life-extending compounds overlooked by the log-rank test in the NIA Interventions Testing Program. GeroScience 2024. PubMed 38630424. Read 2026-10-22.
  9. Strong R et al. Lifespan benefits for the combination of rapamycin plus acarbose and for captopril in genetically heterogeneous mice. Aging Cell 2022. PubMed 36179270. Read 2026-10-22.
  10. Korstanje R et al. Astaxanthin, meclizine, mitoglitazone, pioglitazone, alpha-ketoglutarate, mifepristone, methotrexate, and atorvastatin-telmisartan do not increase lifespan in UM-HET3 mice. GeroScience 2026. PubMed 41843349. Read 2026-10-22.
  11. Strong R et al. Extension of lifespan by epicatechin, halofuginone and mitoglitazone in male but not female genetically heterogeneous mice. GeroScience 2026. PubMed 40973907. Read 2026-10-22.
  12. Miller RA et al. Lifespan effects in male UM-HET3 mice treated with sodium thiosulfate, 16-hydroxyestriol, and late-start canagliflozin. GeroScience 2024. PubMed 38753230. Read 2026-10-22.
Education, not medical advice. This page is for general information. It does not diagnose or treat any condition and is not a substitute for care from a qualified health professional. Natural does not automatically mean safe. Ask a clinician or pharmacist before changing your care, especially if you take medication, are pregnant or breastfeeding, or have a health condition.