The mechanistic target of rapamycin: the grand conducTOR of metabolism and aging
Open accessAbstract
Since the discovery that rapamycin, a small molecule inhibitor of the protein kinase mTOR (mechanistic target of rapamycin), can extend the lifespan of model organisms including mice, interest in understanding the physiological role and molecular targets of this pathway has surged. While mTOR was already well known as a regulator of growth and protein translation, it is now clear that mTOR functions as a central coordinator of organismal metabolism in response to both environmental and hormonal signals. This review discusses recent developments in our understanding of how mTOR signaling is regulated by nutrients and the role of the mTOR signaling pathway in key metabolic tissues. Finally, we discuss the molecular basis for the negative metabolic side effects associated with rapamycin treatment, which may serve as barriers to the adoption of rapamycin or similar compounds for the treatment of diseases of aging and metabolism.
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Rapamycin has earned great interest over the years to prolong lifespan, even when administered to aged animals.
“Additionally, rapamycin has earned great interest over the years to prolong lifespan (195, 280), even when administered to aged animals (281).”
From Metabolic Flexibility as an Adaptation to Energy Resources and Requirements in Health and Disease (2018) · cites this paper as [280]
A family of molecules that are the mechanistic target of the rapamycin (mTOR) complex has been attributed a major role in the biology of cell metabolism, growth, longevity, and even preterm birth.
“A family of molecules that are the mechanistic target of the rapamycin (mTOR) complex has been attributed a major role in the biology of cell metabolism, growth, longevity, and even preterm birth(230–236).”
From Metformin, the Aspirin of the 21st Century: Its Role in Gestational Diabetes Mellitus, Prevention of Preeclampsia and Cancer, and the Promotion of Longevity (2017) · cites this paper as [235]
Rapamycin can prolong the life cycle of many species as diverse as worms and mice, and its signaling system has been implicated as the master regulator of cellular growth and metabolism.
“Rapamycin can also prolong the life cycle of many species as diverse as worms and mice, and its signaling system has been implicated as the master regulator of cellular growth and metabolism.”
From Metformin, the Aspirin of the 21st Century: Its Role in Gestational Diabetes Mellitus, Prevention of Preeclampsia and Cancer, and the Promotion of Longevity (2017) · cites this paper as [235]
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Metabolic Effects of Caloric Restriction
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“Similarly the dietary restriction mimetic rapamycin, which also prolongs healthy lifespan in many species by activating autophagy (Kennedy and Lamming, 2016) and improving mitochondrial complex I function (Miwa et al.”
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- Authors
- Kennedy, B. K., & Lamming, D. W.
- Affiliations
- Buck Institute for Research on Aging (US)
- University of Wisconsin–Madison (US)
- Corresponding author
- Lamming, Dudley W.
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2016-06
- Volume
- 23
- Issue
- 6
- Pages
- 990-1003
- ISSN
- 1550-4131 (ISSN-L)
- PMC
- PMC4910876
- OpenAlex
- W2438502441
- Cited by
- 544
- References
- 172
- Citations by year
- 2026: 39 · 2025: 39 · 2024: 42 · 2023: 48 · 2022: 48 · 2021: 61 · 2020: 53 · 2019: 79 · 2018: 62 · 2017: 58 · 2016: 14
- FWCI
- 6.41
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Glenn Foundation for Medical Research
- National Institutes of Health
- National Institute on Aging (R56AG050441, R01AG050441, R00AG041765)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Keywords
- mTOR signaling, rapamycin, lifespan extension, aging, metabolism, nutrient signaling, hormonal regulation, metabolic tissues, mRNA translation, growth regulation
- MeSH terms
- Aging, Animals, Humans, Metabolism, Organ Specificity, Substrate Specificity, Signal Transduction, TOR Serine-Threonine Kinases
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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