Rapamycin, But Not Resveratrol or Simvastatin, Extends Life Span of Genetically Heterogeneous Mice
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Rapamycin was administered in food to genetically heterogeneous mice from the age of 9 months and produced significant increases in life span, including maximum life span, at each of three test sites. Median survival was extended by an average of 10% in males and 18% in females. Rapamycin attenuated age-associated decline in spontaneous activity in males but not in females. Causes of death were similar in control and rapamycin-treated mice. Resveratrol (at 300 and 1200 ppm food) and simvastatin (12 and 120 ppm) did not have significant effects on survival in male or female mice. Further evaluation of rapamycin's effects on mice is likely to help delineate the role of the mammalian target of rapamycin complexes in the regulation of aging rate and age-dependent diseases and may help to guide a search for drugs that retard some or all of the diseases of aging.
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Rapamycin increases life span and health span and acts as a selective SASP suppressor.
“the mTOR inhibitor rapamycin increases life span and health span (Miller et al. 2011) and acts as a selective SASP suppressor.”
From Senescence and the SASP: many therapeutic avenues (2020) · cites this paper as Miller et al. 2011
The Results report longer life spans in rapamycin-treated male and female mice. The Discussion says activity data only suggest a possible reduction in age-related decline, apparently restricted to males, and calls for further studies of other health outcomes; it does not establish increased health span. The citation precedes the separate SASP-suppressor statement, so that statement is not attributed to this paper. (LLM, conf=0.88)
Experimental — accuracy not yet measuredGenetic regulation of mTOR signal transduction can slow the aging of many organisms.
“Much of the literature suggests that the genetic regulation of mTOR signal transduction can slow the aging of many organisms [183–185].”
From Immunosenescence: a key player in cancer development (2020) · cites this paper as [185]
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RetractedImmunity, stem cells, and aging
Devaraj, E., Anbalagan, M., Ileng Kumaran, R., & Bhaskaran, N. (2021) · Stem Cells and Aging · doi:10.1016/b978-0-12-820071-1.00006-2 · Cited by 8 · see citing works
- Authors
- Miller, R. A., Harrison, D. E., Astle, C. M., Baur, J. A., Boyd, A. R., de Cabo, R., Fernandez, E., Flurkey, K., Javors, M. A., Nelson, J. F., Orihuela, C. J., Pletcher, S., Sharp, Z. D., Sinclair, D., Starnes, J. W., Wilkinson, J. E., Nadon, N. L., & Strong, R.
- Affiliations
- University of Michigan (US)
- Jackson Laboratory (US)
- University of Pennsylvania (US)
- The University of Texas at San Antonio Health Science Center (US)
- Harvard University (US)
- University of North Carolina at Greensboro (US)
- National Institutes of Health (US)
- ORCID
- Venue
- The Journals of Gerontology: Series A
- Publisher
- Oxford University Press (OUP)
- Published
- 2010-10-25
- Volume
- 66A
- Issue
- 2
- Pages
- 191-201
- ISSN
- 1079-5006 (ISSN-L)
- 1758-535X
- PMC
- PMC3021372
- OpenAlex
- W2156003677
- Cited by
- 896
- References
- 51
- Citations by year
- 2026: 31 · 2025: 33 · 2024: 36 · 2023: 52 · 2022: 41 · 2021: 53 · 2020: 53 · 2019: 67 · 2018: 53 · 2017: 53 · 2016: 58 · 2015: 94 · 2014: 79 · 2013: 80 · 2012: 72
- FWCI
- 20.44
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journals of Gerontology Series A (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- The Mouseion at the JAXlibrary (Jackson Laboratory) (submittedVersion)
- Funders
- National Institutes of Health
- National Institute on Aging (U01-AG025707, R37AG028730, P30AG025707, P01AG027916, R01AG028730, R01AG019719, R21AG029313, U01AG022307, P30AG024824, U01AG022308, P30AG038070, U01AG022303)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Keywords
- rapamycin, resveratrol, simvastatin, lifespan extension, aging, genetically heterogeneous mice, mTOR, median survival time, sex differences, age-related mortality, age-related diseases
- MeSH terms
- Resveratrol, Aging, Animals, Female, Longevity, Male, Mice, Inbred BALB C, Mice, Inbred C3H, Mice, Inbred C57BL, Mice, Inbred DBA, Stilbenes, Genetic Heterogeneity, Simvastatin, Sirolimus, Mice
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