Rapamycin appears to be a universal anti-aging drug, extending the lifespan of all animals tested to date; it’s the only known drug to do so.
Inhibiting mTOR with Rapamycin for Extending Lifespan and Healthspan
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Below is an approximation of this video’s audio content. To see any graphs, charts, graphics, images, and quotes to which Dr. Greger may be referring, watch the above video.
The soil bacteria on Easter Island weren’t making rapamycin to slow down aging, but rather to slow down the growth of its natural enemy, soil fungi (just like fungi make penicillin to wipe out competing bacteria). Fungi from yeast on up, like all plants and animals, have mTOR genes. This target of the rapamycin enzyme is the universal growth regulator of advanced lifeforms. So, while rapamycin originally drew attention as an antifungal drug, we soon learned it had many other effects.
Dozens of published studies have demonstrated that rapamycin, by slowing down mTOR, extends both the average and maximum lifespans of laboratory mice. In fact, rapamycin appears to be a universal anti-aging drug, extending the lifespan of all animals and organisms tested to date—the only known drug to do so. It can even work when started in midlife.
The original National Institute on Aging Interventions Testing Program experiment in 2009 was delayed because the researchers were having difficulty keeping rapamycin stable in the mouse food pelleting process. (It can’t just be dissolved in their drinking water because it’s fat soluble.) By the time they were up and running, the allotted batch of mice were 600 days old, which is equivalent to about 60 years of age in humans. Even though the mice started the drug so late in life, their lifespans were still extended by about 12 percent, which could equate to more than an added seven years of human life.
Initially, it was debated whether rapamycin was a true anti-aging intervention or “merely” a potent anticancer agent, lengthening lifespans by just preventing cancer formation. Note that mTOR signaling is hyperactive in up to 80 percent of human cancers, where it plays a pivotal role in sustaining tumor growth. Rapamycin is used clinically to prevent the rejection of organ transplants (by suppressing the proliferation of immune cells that attack the new organ), and a peculiar side effect was found. In a set of 15 patients who had biopsy-proven Kaposi’s sarcoma (a cancer that often affects the skin), all sarcoma skin lesions disappeared in all patients within three months after starting rapamycin therapy. The cancer just vanished. As TOR is the master regulator of cellular growth, the cancer remission was not completely unsurprising, but subsequent rapamycin studies showed it can do so much more.
In animal models, rapamycin extends healthspan too. Rapamycin can ameliorate age-related declines in cognitive function and physical function, prevent hearing loss, artery dysfunction and tendon stiffening, regenerate the periodontal bone that holds teeth in place, and even rejuvenate the hearts of aged mice. Remarkably, health and longevity benefits could be achieved with intermittent or transient dosing, like getting one dose every five days, or for just a few months during middle age.
As a dog dad, I was excited to read about the Dog Aging Project, where people brought their middle-aged companion canines to be randomized to low-dose rapamycin or placebo for 10 weeks. Like in the mouse studies, rapamycin appeared to at least partially reverse some of the age-related heart dysfunction without any untoward side effects. Anecdotally, most of the owners of the dogs who covertly got the rapamycin reported their dogs displayed increased activity and energy compared to only a minority of the owners of the pooches slipped the placebos.
It was time to try rapamycin out in humans, which I’ll cover next.
Please consider volunteering to help out on the site.
- Blagosklonny MV. Does rapamycin slow down time? Oncotarget. 2018;9(54):30210-30212.
- Fleming A. On the antibacterial action of cultures of a penicillium, with special reference to their use in the isolation of b. Influenzæ. Br J Exp Pathol. 1929;10(3):226-236.
- Wei Y, Zhang YJ, Cai Y. Growth or longevity: the TOR’s decision on lifespan regulation. Biogerontology. 2013;14(4):353-363.
- van Dam TJP, Zwartkruis FJT, Bos JL, Snel B. Evolution of the TOR pathway. J Mol Evol. 2011;73(3-4):209-220.
- Swindell WR. Meta-analysis of 29 experiments evaluating the effects of rapamycin on life span in the laboratory mouse. J Gerontol A Biol Sci Med Sci. 2017;72(8):1024-1032.
- Blagosklonny MV. Rapamycin for longevity: opinion article. Aging (Albany NY). 2019;11(19):8048-8067.
- Stallone G, Schena A, Infante B, et al. Sirolimus for Kaposi's sarcoma in renal-transplant recipients. N Engl J Med. 2005 Mar 31;352(13):1317-1323.
- Weichhart T. mTOR as regulator of lifespan, aging, and cellular senescence: a mini-review. Gerontology. 2018;64(2):127-134.
- Sharp ZD, Strong R. The role of mTOR signaling in controlling mammalian life span: what a fungicide teaches us about longevity. J Gerontol A Biol Sci Med Sci. 2010;65(6):580-589.
- Kaeberlein M, Kennedy BK. Ageing: a midlife longevity drug? Nature. 2009;460(7253):331-332.
- Arriola Apelo SI, Lamming DW. Rapamycin: an inhibitor of aging emerges from the soil of easter island. J Gerontol A Biol Sci Med Sci. 2016;71(7):841-849.
- Liu GY, Sabatini DM. mTOR at the nexus of nutrition, growth, ageing and disease. Nat Rev Mol Cell Biol. 2020;21(4):183-203.
- Weber JD, Gutmann DH. Deconvoluting mTOR biology. Cell Cycle. 2012;11(2):236-248.
- Zhang Y, Zhang J, Wang S. The role of rapamycin in healthspan extension via the delay of organ aging. Ageing Res Rev. 2021;70:101376.
- Majumder S, Caccamo A, Medina DX, et al. Lifelong rapamycin administration ameliorates age-dependent cognitive deficits by reducing IL-1β and enhancing NMDA signaling. Aging Cell. 2012;11(2):326-335.
- Wilkinson JE, Burmeister L, Brooks SV, et al. Rapamycin slows aging in mice. Aging Cell. 2012;11(4):675-682.
- Altschuler RA, Kanicki A, Martin C, Kohrman DC, Miller RA. Rapamycin but not acarbose decreases age-related loss of outer hair cells in the mouse Cochlea. Hear Res. 2018;370:11-15.
- Lesniewski LA, Seals DR, Walker AE, et al. Dietary rapamycin supplementation reverses age-related vascular dysfunction and oxidative stress, while modulating nutrient-sensing, cell cycle, and senescence pathways. Aging Cell. 2017;16(1):17-26.
- Zaseck LW, Miller RA, Brooks SV. Rapamycin attenuates age-associated changes in tibialis anterior tendon viscoelastic properties. J Gerontol A Biol Sci Med Sci. 2016;71(7):858-865.
- An JY, Kerns KA, Ouellette A, et al. Rapamycin rejuvenates oral health in aging mice. Elife. 2020;9:e54318.
- Dai DF, Karunadharma PP, Chiao YA, et al. Altered proteome turnover and remodeling by short-term caloric restriction or rapamycin rejuvenate the aging heart. Aging Cell. 2014;13(3):529-539.
- Arriola Apelo SI, Pumper CP, Baar EL, Cummings NE, Lamming DW. Intermittent administration of rapamycin extends the life span of female C57BL/6J mice. J Gerontol A Biol Sci Med Sci. 2016;71(7):876-881.
- Bitto A, Ito TK, Pineda VV, et al. Transient rapamycin treatment can increase lifespan and healthspan in middle-aged mice. Elife. 2016;5:e16351.
- Kaeberlein M, Creevy KE, Promislow DEL. The dog aging project: translational geroscience in companion animals. Mamm Genome. 2016;27(7-8):279-288.
- Urfer SR, Kaeberlein TL, Mailheau S, et al. A randomized controlled trial to establish effects of short-term rapamycin treatment in 24 middle-aged companion dogs. Geroscience. 2017;39(2):117-127.
Motion graphics by Avo Media
Below is an approximation of this video’s audio content. To see any graphs, charts, graphics, images, and quotes to which Dr. Greger may be referring, watch the above video.
The soil bacteria on Easter Island weren’t making rapamycin to slow down aging, but rather to slow down the growth of its natural enemy, soil fungi (just like fungi make penicillin to wipe out competing bacteria). Fungi from yeast on up, like all plants and animals, have mTOR genes. This target of the rapamycin enzyme is the universal growth regulator of advanced lifeforms. So, while rapamycin originally drew attention as an antifungal drug, we soon learned it had many other effects.
Dozens of published studies have demonstrated that rapamycin, by slowing down mTOR, extends both the average and maximum lifespans of laboratory mice. In fact, rapamycin appears to be a universal anti-aging drug, extending the lifespan of all animals and organisms tested to date—the only known drug to do so. It can even work when started in midlife.
The original National Institute on Aging Interventions Testing Program experiment in 2009 was delayed because the researchers were having difficulty keeping rapamycin stable in the mouse food pelleting process. (It can’t just be dissolved in their drinking water because it’s fat soluble.) By the time they were up and running, the allotted batch of mice were 600 days old, which is equivalent to about 60 years of age in humans. Even though the mice started the drug so late in life, their lifespans were still extended by about 12 percent, which could equate to more than an added seven years of human life.
Initially, it was debated whether rapamycin was a true anti-aging intervention or “merely” a potent anticancer agent, lengthening lifespans by just preventing cancer formation. Note that mTOR signaling is hyperactive in up to 80 percent of human cancers, where it plays a pivotal role in sustaining tumor growth. Rapamycin is used clinically to prevent the rejection of organ transplants (by suppressing the proliferation of immune cells that attack the new organ), and a peculiar side effect was found. In a set of 15 patients who had biopsy-proven Kaposi’s sarcoma (a cancer that often affects the skin), all sarcoma skin lesions disappeared in all patients within three months after starting rapamycin therapy. The cancer just vanished. As TOR is the master regulator of cellular growth, the cancer remission was not completely unsurprising, but subsequent rapamycin studies showed it can do so much more.
In animal models, rapamycin extends healthspan too. Rapamycin can ameliorate age-related declines in cognitive function and physical function, prevent hearing loss, artery dysfunction and tendon stiffening, regenerate the periodontal bone that holds teeth in place, and even rejuvenate the hearts of aged mice. Remarkably, health and longevity benefits could be achieved with intermittent or transient dosing, like getting one dose every five days, or for just a few months during middle age.
As a dog dad, I was excited to read about the Dog Aging Project, where people brought their middle-aged companion canines to be randomized to low-dose rapamycin or placebo for 10 weeks. Like in the mouse studies, rapamycin appeared to at least partially reverse some of the age-related heart dysfunction without any untoward side effects. Anecdotally, most of the owners of the dogs who covertly got the rapamycin reported their dogs displayed increased activity and energy compared to only a minority of the owners of the pooches slipped the placebos.
It was time to try rapamycin out in humans, which I’ll cover next.
Please consider volunteering to help out on the site.
- Blagosklonny MV. Does rapamycin slow down time? Oncotarget. 2018;9(54):30210-30212.
- Fleming A. On the antibacterial action of cultures of a penicillium, with special reference to their use in the isolation of b. Influenzæ. Br J Exp Pathol. 1929;10(3):226-236.
- Wei Y, Zhang YJ, Cai Y. Growth or longevity: the TOR’s decision on lifespan regulation. Biogerontology. 2013;14(4):353-363.
- van Dam TJP, Zwartkruis FJT, Bos JL, Snel B. Evolution of the TOR pathway. J Mol Evol. 2011;73(3-4):209-220.
- Swindell WR. Meta-analysis of 29 experiments evaluating the effects of rapamycin on life span in the laboratory mouse. J Gerontol A Biol Sci Med Sci. 2017;72(8):1024-1032.
- Blagosklonny MV. Rapamycin for longevity: opinion article. Aging (Albany NY). 2019;11(19):8048-8067.
- Stallone G, Schena A, Infante B, et al. Sirolimus for Kaposi's sarcoma in renal-transplant recipients. N Engl J Med. 2005 Mar 31;352(13):1317-1323.
- Weichhart T. mTOR as regulator of lifespan, aging, and cellular senescence: a mini-review. Gerontology. 2018;64(2):127-134.
- Sharp ZD, Strong R. The role of mTOR signaling in controlling mammalian life span: what a fungicide teaches us about longevity. J Gerontol A Biol Sci Med Sci. 2010;65(6):580-589.
- Kaeberlein M, Kennedy BK. Ageing: a midlife longevity drug? Nature. 2009;460(7253):331-332.
- Arriola Apelo SI, Lamming DW. Rapamycin: an inhibitor of aging emerges from the soil of easter island. J Gerontol A Biol Sci Med Sci. 2016;71(7):841-849.
- Liu GY, Sabatini DM. mTOR at the nexus of nutrition, growth, ageing and disease. Nat Rev Mol Cell Biol. 2020;21(4):183-203.
- Weber JD, Gutmann DH. Deconvoluting mTOR biology. Cell Cycle. 2012;11(2):236-248.
- Zhang Y, Zhang J, Wang S. The role of rapamycin in healthspan extension via the delay of organ aging. Ageing Res Rev. 2021;70:101376.
- Majumder S, Caccamo A, Medina DX, et al. Lifelong rapamycin administration ameliorates age-dependent cognitive deficits by reducing IL-1β and enhancing NMDA signaling. Aging Cell. 2012;11(2):326-335.
- Wilkinson JE, Burmeister L, Brooks SV, et al. Rapamycin slows aging in mice. Aging Cell. 2012;11(4):675-682.
- Altschuler RA, Kanicki A, Martin C, Kohrman DC, Miller RA. Rapamycin but not acarbose decreases age-related loss of outer hair cells in the mouse Cochlea. Hear Res. 2018;370:11-15.
- Lesniewski LA, Seals DR, Walker AE, et al. Dietary rapamycin supplementation reverses age-related vascular dysfunction and oxidative stress, while modulating nutrient-sensing, cell cycle, and senescence pathways. Aging Cell. 2017;16(1):17-26.
- Zaseck LW, Miller RA, Brooks SV. Rapamycin attenuates age-associated changes in tibialis anterior tendon viscoelastic properties. J Gerontol A Biol Sci Med Sci. 2016;71(7):858-865.
- An JY, Kerns KA, Ouellette A, et al. Rapamycin rejuvenates oral health in aging mice. Elife. 2020;9:e54318.
- Dai DF, Karunadharma PP, Chiao YA, et al. Altered proteome turnover and remodeling by short-term caloric restriction or rapamycin rejuvenate the aging heart. Aging Cell. 2014;13(3):529-539.
- Arriola Apelo SI, Pumper CP, Baar EL, Cummings NE, Lamming DW. Intermittent administration of rapamycin extends the life span of female C57BL/6J mice. J Gerontol A Biol Sci Med Sci. 2016;71(7):876-881.
- Bitto A, Ito TK, Pineda VV, et al. Transient rapamycin treatment can increase lifespan and healthspan in middle-aged mice. Elife. 2016;5:e16351.
- Kaeberlein M, Creevy KE, Promislow DEL. The dog aging project: translational geroscience in companion animals. Mamm Genome. 2016;27(7-8):279-288.
- Urfer SR, Kaeberlein TL, Mailheau S, et al. A randomized controlled trial to establish effects of short-term rapamycin treatment in 24 middle-aged companion dogs. Geroscience. 2017;39(2):117-127.
Motion graphics by Avo Media
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Title
Inhibiting mTOR with Rapamycin for Extending Lifespan and Healthspan
LicenseCreative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0)
Content URLDoctor's Note
This is the second video in a three-part series. If you missed the first one, check out The Enzyme mTOR as an Engine of Aging, and stay tuned for Is Rapamycin a Universal Anti-Aging Drug?.
For more on longevity, see:
- Is Longevity Genetic?
- Dietary Sources of the “Longevity Vitamin” Ergothioneine
- APOE—The Single Most Important Gene for Longevity
For more on aging, visit your local public library or book seller and check out my longevity book, How Not to Age, available in print, e-book, and audio. (All proceeds I receive from the book are donated directly to charity.)
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