Cited by 544PI3K/AKT/mTOR signaling in cancerGenetics, Aging, and Longevity in Model OrganismsMetabolism, Diabetes, and Cancer

The mechanistic target of rapamycin: the grand conducTOR of metabolism and aging

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Kennedy, Brian K., Lamming, Dudley W.·2016·Cell Metabolism

Abstract

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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Crossref · 10.1016/j.cmet.2016.05.009

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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)
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
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

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