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    How anti-aging interventions are tested, from mice to people

    Anti-aging interventions are first tested for lifespan in animals such as genetically diverse mice, then in people against specific diseases or composite outcomes, because the FDA does not recognize aging as a disease.[1][2][3] Dogs have become a middle step, with both a rapamycin trial and a lifespan drug under FDA review.[4][5]

    Editor reviewedStrict sourcingUpdated Aging and longevity biologyLife sciencesHealth and medicine

    Step one: lifespan in animals

    Most ideas start in short-lived animals such as mice. The US National Institute on Aging’s testing program, started in 2004, runs studies at several sites at once with genetically mixed mice. Results therefore do not depend on one lab or one mouse strain.[1] It has tested 54 substances in more than 30,000 mice.[6]

    The interventions-testing-program uses UM-HET3 mice across multiple sites, a design meant to avoid effects specific to one genotype or one lab.[1] Its best-known positive result, rapamycin, replicated at three independent sites.[7] Statistical choices matter: a 2024 reanalysis with the Gehan test found survival benefits, including for metformin in males, that the standard log-rank test had missed.[8] Most ITP compounds that worked did so mainly in males, a reminder that sex is a major variable.[9]

    Step two: companion dogs

    Companion dogs share the human environment and have shorter lives than people, which allows faster tests of interventions.[10] TRIAD is a randomized, placebo-controlled trial of rapamycin in healthy middle-aged pet dogs from the Dog Aging Project.[4] Its designers call it the first rigorous lifespan-and-healthspan test of an anti-aging drug outside the laboratory in any species.[11] TRIAD plans to enrol 580 dogs and uses survival time as its primary outcome.[12] Separately, Loyal’s loy-002 is the subject of a 1,317-dog study and has cleared two of three major FDA requirements for conditional approval.[13][5] Loyal says the FDA has accepted effectiveness sections for two other lifespan drugs aimed at large dogs, LOY-001 and LOY-003.[14]

    Step three: people, without an aging indication

    In people, the FDA does not recognize aging as a disease, and a 2025 scoping review found no regulatory framework for approving drugs that target aging, so such drugs are developed for specific diseases.[3] Researchers therefore borrow other routes. The planned tame-trial of the diabetes drug metformin would track whether people develop any of several age-related diseases (heart events, cancer, dementia) or die, rather than one disease.[2] Life Biosciences’ rejuvenation therapy er-100 is being tested in two eye diseases rather than in aging.[15]

    Three human strategies are in use. First, composite-endpoint trials: TAME was designed for 3,000 people aged 65–79, measuring time to a first new cardiovascular event, cancer, dementia or death.[16][2] Second, disease-specific proxies for an aging mechanism, such as ER-100 in glaucoma and NAION, or senolytics in pulmonary fibrosis and diabetic macular edema.[15][17][18] Third, functional endpoints in older adults, such as vaccine response under mTOR inhibition.[19] Prize programmes also push trials: XPRIZE Healthspan finalists must be ready to run randomized trials in 100–200 participants.[20]

    Why biomarkers matter here

    Biomarkers of aging could serve as surrogate endpoints, but as of 2024 there was no consensus on how to validate them.[21] Until then, a conclusive test of the geroscience hypothesis requires long trials with hard endpoints.[22]

    Common pitfalls

    Two examples show why trial design matters. A 14-person open-label senolytic study reported better physical function.[17] A later 60-person randomized senolytic trial in a different condition missed its primary endpoint.[23] Separately, the mTOR inhibitor RTB101 did not reduce respiratory illness in a 1,024-person phase 3 trial.[24] Next in the course: senolytics.

    Questions readers ask

    Why not just run a trial to see if a drug makes people live longer?

    Lifespan trials in people would take a very long time. A conclusive test needs long-term follow-up with outcomes such as chronic disease and death, which is why researchers look for shorter proxies.[22]

    Can a company get a drug approved for aging?

    Not in people today. The FDA does not recognize aging as a disease and no regulatory framework exists for approving aging-targeted therapies, so trials target specific conditions.[3]

    Why are dogs used in aging research?

    Companion dogs share our environment and live shorter lives, which allows faster tests. TRIAD tests rapamycin in middle-aged pet dogs, and Loyal's LOY-002 is in a 1,300-dog study.[10][4][25]

    What is the NIA Interventions Testing Program?

    A US government-funded program, running since 2004, that tests candidate compounds for lifespan effects in genetically diverse mice at multiple sites.[1]

    Sources

    Each numbered claim is a statement we checked against the sources listed with it. Status shows how well established it is.

    1. [1]

      The US National Institute on Aging launched the Interventions Testing Program (ITP) in 2004 as a multi-site effort testing candidate compounds in genetically heterogeneous UM-HET3 mice. confirmedas of 2025-07-24

    2. [2]

      TAME's primary measure is time to a new occurrence of a composite of cardiovascular events, cancer, dementia and death, rather than any single disease. confirmedas of 2016-06-14

    3. [3]

      Papers published in 2025 in peer-reviewed journals state that the FDA does not recognize aging as a disease and that no regulatory framework exists for developing or approving therapies that target aging, so such therapies are developed through disease-specific pipelines. confirmedas of 2025-08-04

    4. [4]

      TRIAD is a double-masked, randomized, placebo-controlled multicenter trial testing whether rapamycin extends lifespan and improves healthspan in healthy middle-aged companion dogs from the Dog Aging Project. confirmedas of 2025-02-14

    5. [5]

      The manufacturing section must still be accepted before LOY-002 can be considered for conditional approval; as of October 2026 Loyal says two of three major requirements are complete and approval is not guaranteed. confirmedas of 2026-10-10

    6. [6]

      Over two decades the ITP has tested 54 agents in more than 30,000 mice. confirmedas of 2025-07-24

    7. [7]

      Measured by age at 90% mortality, rapamycin increased lifespan by 14% in female and 9% in male mice, with the effect seen at three independent test sites using genetically heterogeneous mice chosen to avoid genotype-specific effects. confirmedas of 2009-07-08

    8. [8]

      A 2024 reanalysis of ITP data from 2004 to 2022 with the Gehan test, which is more sensitive to mortality differences earlier in life, found that metformin, previously missed by the log-rank test, increased survival in male mice only. confirmedas of 2024-04-17

    9. [9]

      Most compounds that extended lifespan in the ITP worked primarily or only in male mice. confirmedas of 2025-07-24

    10. [10]

      Companion dogs are considered a useful aging model because they share the human environment and have shorter life expectancy than people, allowing faster tests of interventions. confirmedas of 2025-02-14

    11. [11]

      Its designers describe TRIAD as the first rigorous test of a drug against biological aging with lifespan and healthspan endpoints performed outside the laboratory in any species. confirmedas of 2025-02-14

    12. [12]

      TRIAD plans to enrol and randomize 580 dogs, with survival time from randomization as its primary outcome. confirmedas of 2025-02-14

    13. [13]

      As of October 2026 Loyal's website lists 1,317 dogs enrolled in the STAY trial at 70 veterinary practices and three drug programs in development. confirmedas of 2026-10-10

    14. [14]

      On 16 September 2026 Loyal said the FDA had accepted the reasonable expectation of effectiveness (RXE) for LOY-003, a once-daily tablet meant to extend the lifespan of large and giant-breed dogs by lowering growth hormone and IGF-1; Loyal says this is its third RXE, after LOY-001 and LOY-002. reportedas of 2026-09-16

    15. [15]

      On 9 June 2026 Life Biosciences announced the first patient dosed in its Phase 1 trial of ER-100 (NCT07290244) in open-angle glaucoma and non-arteritic anterior ischemic optic neuropathy (NAION), which evaluates safety and tolerability with additional visual-function endpoints. confirmedas of 2026-06-09

    16. [16]

      The TAME (Targeting Aging with Metformin) trial was designed in 2016 to enrol 3,000 people aged 65 to 79 at about 14 US centres. confirmedas of 2016-06-14

    17. [17]

      The first-in-human senolytic study, an open-label pilot of dasatinib plus quercetin in 14 people with idiopathic pulmonary fibrosis, reported improved physical function but no change in lung function or frailty index. confirmedas of 2019-01-05

    18. [18]

      In a 65-person sham-controlled trial in diabetic macular edema, UBX1325 showed a non-significant 5.6-letter visual acuity advantage at 48 weeks, and the authors called for larger trials. confirmedas of 2025-04-22

    19. [19]

      In a 2014 trial in older volunteers, the mTOR inhibitor RAD001 (everolimus) improved the response to influenza vaccination by about 20% at relatively well-tolerated doses. confirmedas of 2014-12-24

    20. [20]

      Teams in the XPRIZE Healthspan finals must be prepared to run randomized controlled clinical trials in 100 to 200 participants. confirmedas of 2026-10-10

    21. [21]

      Aging biomarkers could serve as surrogate endpoints for trials of longevity interventions, but as of 2024 there was no consensus on how they should be validated before clinical use. confirmedas of 2024-02-14

    22. [22]

      Researchers note that a conclusive test of the geroscience hypothesis requires long trials measuring hard endpoints such as chronic disease incidence and mortality. confirmedas of 2023-02-09

    23. [23]

      In a 2024 phase 2 randomized trial in 60 postmenopausal women, intermittent dasatinib plus quercetin did not change the primary bone-resorption marker at 20 weeks compared with control. confirmedas of 2024-07-02

    24. [24]

      In a phase 3 trial of 1,024 adults aged 65 or older, the mTOR inhibitor RTB101 did not reduce clinically symptomatic respiratory illness compared with placebo. confirmedas of 2021-05-06

    25. [25]

      Loyal's STAY study of LOY-002 completed enrolment of about 1,300 dogs at 70 US veterinary clinics in July 2025. confirmedas of 2026-01-13

    Revision history (2)
    1. Page created.
    2. Refresh: added TRIAD's planned size, the updated STAY enrolment and Loyal's LOY-003.

    Created Oct 10, 2026. Last reviewed by an editor on Oct 10, 2026. Next scheduled review: Jan 10, 2027.

    Cite this page

    "How anti-aging interventions are tested, from mice to people." ContentLora, updated Oct 10, 2026. https://contentlora.com/explain/how-aging-interventions-are-tested

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