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    Rapamycin and mTOR inhibition

    Also known as rapamycin, sirolimus, mTOR inhibitors, rapalogs

    Rapamycin inhibits mTOR, a nutrient-sensing pathway whose inhibition has extended lifespan in every species studied, including mice of both sexes in a landmark 2009 study.[1][2] Human trials have tested immune function and safety in healthy adults, with mixed results and no approval for aging as of October 2026.[3][4][5]

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

    What mTOR is and why it matters

    mTOR (mechanistic target of rapamycin) is a central nutrient-sensing pathway, and deregulated nutrient sensing is one of the twelve hallmarks of aging.[6] By 2014, inhibiting mTOR had extended lifespan in all species studied.[1]

    The landmark mouse study

    In 2009, mice fed rapamycin from 600 days of age lived longer, with both median and maximal lifespan extended in males and females.[2] Measured by age at 90% mortality, the gains were 14% in females and 9% in males. The result replicated at three independent sites using genetically diverse mice.[7] The authors described these as the first results showing pharmacological lifespan extension in both sexes of a mammal.[2] A separate study starting at 270 days of age also increased survival in an interim analysis.[8] The authors said rapamycin might work by postponing death from cancer, by slowing aging, or both.[9] Rapamycin is one of the best-known positive results of the NIA’s interventions-testing-program. A 2025 review of that program found it was the only one of 13 lifespan-extending compounds that worked better in females than in males.[10]

    Later mouse work asked whether treatment must be lifelong. A 2016 study found that just three months of rapamycin in middle-aged mice increased life expectancy by up to 60% and improved healthspan measures. It also found a dose in females that did not extend lifespan but shifted cancers toward aggressive blood cancers.[11]

    Human studies

    Human trials have tested specific functions rather than lifespan. In 2014, the mTOR inhibitor everolimus (RAD001) improved older volunteers’ response to flu vaccination by about 20% at relatively well-tolerated doses.[3] A later phase 3 trial of a different mTOR inhibitor, RTB101, in 1,024 adults aged 65 and over did not reduce clinically symptomatic respiratory illness.[4]

    The PEARL trial, published in 2025, gave healthy adults weekly low-dose rapamycin (5 mg or 10 mg) or placebo for 48 weeks.[12] Adverse events were similar across groups and visceral fat, the primary outcome, did not change. Some secondary measures improved, such as lean tissue mass and pain in women on 10 mg.[5] Several authors disclosed employment at and shares in AgelessRx.[13]

    Dogs and the road ahead

    TRIAD, a randomized placebo-controlled trial in healthy middle-aged pet dogs, is testing whether rapamycin extends lifespan and healthspan outside the laboratory.[14][15] It plans to enrol 580 dogs, with survival time from randomization as the primary outcome.[16] Earlier small studies in dogs, including 24 and 17 healthy middle-aged dogs and 152 dogs with bone cancer, found a low rate of side effects similar to control groups.[17] Dogs share the human environment and live shorter lives, so a trial can report faster than one in people.[18] Loyal’s separate dog-drug programs, such as loy-002, target other pathways.[19]

    Industry interest continues. Joan Mannick, who co-founded resTORbio and later ran Tornado Therapeutics, a company developing mTOR inhibitors for aging-related diseases, became Chief Medical Officer of altos-labs.[20][21] In people, the FDA does not recognize aging as a disease and no regulatory framework exists for approving aging-targeted therapies, so rapamycin-based drugs would be developed for specific diseases.[22]

    This page describes research findings and is not medical advice.

    Questions readers ask

    Does rapamycin extend lifespan in mice?

    Yes. In a 2009 study it extended median and maximal lifespan in male and female mice even when started at 600 days of age, with effects at three independent sites.[2][7]

    Has rapamycin been shown to slow aging in people?

    No. The 48-week PEARL trial in healthy adults found adverse events similar to placebo but no change in its primary outcome, visceral fat.[5]

    Is rapamycin being tested in dogs?

    Yes. TRIAD is a randomized, placebo-controlled trial of rapamycin in healthy middle-aged pet dogs from the Dog Aging Project.[14]

    Sources

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

    1. [1]

      Inhibiting the mTOR pathway has extended lifespan in every species studied, as of a 2014 review of the evidence. confirmedas of 2014-12-24

    2. [2]

      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

    3. [3]

      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

    4. [4]

      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

    5. [5]

      In PEARL, adverse events were similar across groups and the primary outcome, visceral fat, did not change significantly; some secondary measures improved, such as lean tissue mass and pain in women on 10 mg. confirmedas of 2025-04-04

    6. [6]

      A 2023 update in Cell expanded the list to twelve hallmarks of aging: genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, disabled macroautophagy, deregulated nutrient-sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, altered intercellular communication, chronic inflammation and dysbiosis. confirmedas of 2026-10-10

    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]

      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

    9. [9]

      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

    10. [10]

      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

    11. [11]

      A 2016 study found that three months of rapamycin in middle-aged mice increased life expectancy by up to 60% and improved healthspan measures, while one dose in females that did not extend lifespan shifted cancers toward aggressive blood cancers. confirmedas of 2016-08-23

    12. [12]

      PEARL was a 48-week double-blind, randomized, placebo-controlled trial of weekly low-dose rapamycin (5 mg or 10 mg) in healthy, normally aging adults. confirmedas of 2025-04-04

    13. [13]

      Several PEARL authors disclosed that they are employees and shareholders of AgelessRx, a company that provides longevity-focused prescriptions. confirmedas of 2025-04-04

    14. [14]

      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

    15. [15]

      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

    16. [16]

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

    17. [17]

      Earlier small studies giving rapamycin to dogs, including 24 and 17 healthy middle-aged dogs and 152 dogs with osteosarcoma, found a low incidence of adverse events similar to control groups. confirmedas of 2025-02-14

    18. [18]

      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

    19. [19]

      LOY-002 targets dogs aged 10 or older weighing at least 14 pounds and is intended to work by improving insulin sensitivity and lowering insulin levels. confirmedas of 2026-10-10

    20. [20]

      Joan Mannick joined Altos Labs from Tornado Therapeutics, where she was chief executive and co-founder developing mTOR inhibitors for aging-related diseases; she earlier held leadership roles at Life Biosciences, resTORbio, which she co-founded, and a Novartis unit running clinical programs targeting aging biology. confirmedas of 2026-10-10

    21. [21]

      Altos Labs appointed Joan Mannick as Chief Medical Officer and Head of Product Development to help bring its rejuvenation science to patients. confirmedas of 2026-10-10

    22. [22]

      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

    23. [23]

      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

    24. [24]

      The authors of the 2023 hallmarks review describe the twelve hallmarks as interconnected with one another. confirmedas of 2026-10-10

    Revision history (2)
    1. Page created.
    2. Refresh: added the 2016 transient-rapamycin mouse study, the ITP review's sex finding, TRIAD's size and earlier dog safety data, and industry context.

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

    Cite this page

    "Rapamycin and mTOR inhibition." ContentLora, updated Oct 10, 2026. https://contentlora.com/wiki/rapamycin-and-mtor

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