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    NIA Interventions Testing Program (ITP)

    Also known as ITP, NIA ITP, Interventions Testing Program

    The Interventions Testing Program is a US National Institute on Aging effort, started in 2004, that tests candidate compounds for lifespan effects in genetically diverse UM-HET3 mice at multiple sites.[1] It has tested 54 agents in more than 30,000 mice. Rapamycin and acarbose are among its positive results, and most effective compounds worked mainly in males.[2][3][4]

    Editor reviewedStrict sourcingUpdated Aging and longevity biologyLife sciencesHealth and medicine
    Key facts

    What the ITP is

    The Interventions Testing Program (ITP) was launched by the US National Institute on Aging in 2004 to find compounds that extend lifespan and delay aging. It runs the same studies at multiple sites using genetically heterogeneous UM-HET3 mice.[1] Over two decades it has tested 54 agents in more than 30,000 mice.[2]

    Each year the program takes proposals from researchers worldwide and selects the most promising interventions to test.[5] Its UM-HET3 mice are bred by crossing four common inbred strains, so each animal has a unique genetic background that mimics the genetic diversity of people.[5] To limit the influence of any one lab’s environment, each compound is tested at three different locations, and results are judged with the log-rank test for overall lifespan and the Wang-Allison test for maximum lifespan.[6] Genetically heterogeneous mice are used to avoid genotype-specific effects. In the landmark rapamycin study, the effect was seen at three independent sites.[7]

    Key results

    Using its standard log-rank test, the ITP had identified 12 lifespan-extending compounds by 2024. Notable examples include rapamycin and acarbose.[8][3] Rapamycin, fed from 600 days of age, extended lifespan in both sexes in 2009.[9] A separate study starting at 270 days also increased survival in both sexes in an interim analysis.[10] The authors noted that rapamycin might work by postponing cancer deaths, by slowing aging, or both, a question that applies to many lifespan results.[11] See rapamycin-and-mtor.

    A 2024 reanalysis of ITP data from 2004 to 2022 used the Gehan test, which is more sensitive to early-life differences in mortality. It found five additional compounds that increased survival. Metformin was among them, effective in males only.[12] Three of the five (metformin, enalapril and 17-DMAG) worked only in males, and two (CAPE and green tea extract) only in females.[12] That nuance matters for the metformin-based tame-trial in people.

    Replication is uneven. As of 2025, nine of the lifespan-extending compounds, including captopril, the diabetes drug canagliflozin, astaxanthin, aspirin and glycine, had been tested in only a single cohort.[13] A single positive cohort is a weaker signal than a result repeated across cohorts and sites.

    The sex-difference pattern

    A 2025 review of two decades of ITP results found that most compounds that extended lifespan were effective primarily or exclusively in male mice.[4] By its count, 13 compounds significantly prolonged lifespan in at least one sex. Rapamycin was the only one that worked better in females. Acarbose, captopril and 1,3-butanediol worked better in males, and eight others, including aspirin, canagliflozin, 17-alpha-estradiol and astaxanthin, worked only in males.[14] The two female-only compounds from the 2024 reanalysis are further exceptions.[3] The review’s authors say dose and the age at which treatment starts also affect results differently in each sex, which suggests that aging mechanisms themselves differ by sex.[15]

    Why it matters for the field

    Mouse lifespan results are a first filter for candidates. Drugs that look promising can move on to companion dogs, as rapamycin has in the TRIAD trial.[16] Human trials target specific diseases because the FDA does not recognize aging as a disease and no regulatory framework exists for approving aging-targeted therapies.[17] For how candidates move from mice to dogs and people, see how aging interventions are tested.

    Questions readers ask

    Why does the ITP use genetically diverse mice?

    To avoid genotype-specific effects. The landmark rapamycin study used such mice and replicated at three independent sites.[1][7]

    Did metformin extend lifespan in the ITP?

    Not by the program's standard test. A 2024 reanalysis using a different statistical test found a survival benefit in male mice only.[12]

    Do ITP drugs work equally in both sexes?

    Usually not. Most compounds that extended lifespan worked primarily or only in males.[4]

    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]

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

    3. [3]

      Rapamycin and acarbose are among the twelve of 48 drugs that extended mouse lifespan in the ITP under its standard tests; apart from two compounds found effective only in females in a 2024 reanalysis, rapamycin is the only ITP drug that has worked better in females. confirmedas of 2024-04-17

    4. [4]

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

    5. [5]

      Each year the ITP accepts proposals from researchers worldwide and picks the most promising interventions to test in UM-HET3 mice, which are bred from four inbred strains so that each mouse has a unique genetic background, mimicking human genetic diversity. confirmedas of 2025-07-24

    6. [6]

      To minimise environmental effects, the ITP tests each compound at three different locations, and after each cohort it applies the log-rank test for lifespan and the Wang-Allison test for maximum lifespan. 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]

      Using its standard log-rank test, the ITP had identified 12 compounds that extend the lifespan of genetically heterogeneous mice as of 2024. confirmedas of 2024-04-17

    9. [9]

      In 2009 rapamycin, an inhibitor of the mTOR pathway, extended median and maximal lifespan in both male and female mice when feeding began at 600 days of age, the first drug shown to extend lifespan in both sexes of a mammal. confirmedas of 2009-07-08

    10. [10]

      In a separate 2009 study, rapamycin started at 270 days of age also increased survival in both male and female mice, based on an interim analysis. confirmedas of 2009-07-08

    11. [11]

      The authors of the 2009 rapamycin study said it may extend lifespan by postponing death from cancer, by slowing mechanisms of aging, or both. confirmedas of 2009-07-08

    12. [12]

      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

    13. [13]

      As of 2025, nine of the ITP's lifespan-extending compounds, including captopril, canagliflozin, astaxanthin, aspirin and glycine, had been tested in only a single cohort. confirmedas of 2025-07-24

    14. [14]

      A 2025 review of two decades of ITP results counted 13 compounds that significantly prolonged lifespan in at least one sex; rapamycin was the only one that worked better in females, and eight, including aspirin, canagliflozin, 17-alpha-estradiol and astaxanthin, worked only in males. confirmedas of 2025-07-24

    15. [15]

      The 2025 ITP review found that dose and the age at which treatment started affected efficacy, also differently by sex, and its authors concluded that mechanisms of aging may be sexually dimorphic. confirmedas of 2025-07-24

    16. [16]

      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

    17. [17]

      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

    Revision history (2)
    1. Page created.
    2. Refresh: added how compounds are chosen, the 2025 review's 13-compound count and sex breakdown, single-cohort caveats and dose and onset effects.

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

    Cite this page

    "NIA Interventions Testing Program (ITP)." ContentLora, updated Oct 10, 2026. https://contentlora.com/wiki/interventions-testing-program

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