mTOR as Regulator of Lifespan, Aging, and Cellular Senescence: A Mini-Review
Open accessAbstract
The mechanistic target of rapamycin (mTOR) network is an evolutionary conserved signaling hub that senses and integrates environmental and intracellular nutrient and growth factor signals to coordinate basic cellular and organismal responses such as cell growth, proliferation, apoptosis, and inflammation depending on the individual cell and tissue. A growing list of evidence suggests that mTOR signaling influences longevity and aging. Inhibition of the mTOR complex 1 (mTORC1) with rapamycin is currently the only known pharmacological treatment that increases lifespan in all model organisms studied. This review discusses the potential mechanisms how mTOR signaling controls lifespan and influences aging-related processes such as cellular senescence, metabolism, and stem cell function. Understanding these processes might provide novel therapeutic approaches to influence longevity and aging-related diseases.
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Cellular senescence is associated with changes in cellular metabolism including upregulation of lysosomal senescence-associated β-galactosidase, a shift from oxidative phosphorylation to glycolysis, and accumulation of lipofuscin in the cytoplasm.
“Cellular senescence is associated with changes in cellular metabolism. These include upregulation of lysosomal senescence-associated β-galactosidase, a shift from oxidative phosphorylation to glycolysis [54,55] and accumulation of lipofuscin in the cytoplasm [56,57].”
From Ageing, Cellular Senescence and Neurodegenerative Disease (2018) · cites this paper as [55]
The senescence-associated secretory phenotype consists of pro-inflammatory cytokines, proteases, chemokines, and extracellular matrix degrading proteins.
“The SASP consists of a noxious secretome comprised of pro-inflammatory cytokines, proteases, chemokines, and extracellular matrix degrading proteins (24–27).”
From Senolytic Therapy to Modulate the Progression of Alzheimer's Disease (SToMP-AD): A Pilot Clinical Trial (2022) · cites this paper as [27]
mTORC2 controls cell proliferation and survival by the phosphorylation of several protein kinases, including AKT and SGK1.
“mTORC2 controls cell proliferation and survival by the phosphorylation of several protein kinases, including AKT and SGK1.”
From The mitochondrial permeability transition: Nexus of aging, disease and longevity (2021) · cites this paper as [150]
The mTOR pathway controls autophagy and thus lifespan.
“Another nutrient-sensing pathway that controls autophagy and thus lifespan is the mTOR pathway [148,149,150,151,152].”
From The mitochondrial permeability transition: Nexus of aging, disease and longevity (2021) · cites this paper as [150]
mTORC1 regulates cell growth and metabolism and negatively regulates autophagy.
“mTORC1 regulates cell growth and metabolism and negatively regulates autophagy.”
From The mitochondrial permeability transition: Nexus of aging, disease and longevity (2021) · cites this paper as [150]
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- Authors
- Weichhart, T.
- Affiliations
- Medical University of Vienna (AT)
- Corresponding author
- Weichhart, Thomas
- ORCID
- Weichhart, Thomas
- Venue
- Gerontology
- Publisher
- S. Karger AG
- Published
- 2017-12-01
- Volume
- 64
- Issue
- 2
- Pages
- 127-134
- ISSN
- 0304-324X (ISSN-L)
- 1423-0003
- PMC
- PMC6089343
- OpenAlex
- W2774620560
- Cited by
- 596
- References
- 65
- Citations by year
- 2026: 37 · 2025: 75 · 2024: 92 · 2023: 83 · 2022: 98 · 2021: 97 · 2020: 62 · 2019: 37 · 2018: 15
- FWCI
- 3.50
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Gerontology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Keywords
- mTOR signaling, lifespan, aging, cellular senescence, mTORC1, rapamycin, longevity, metabolism, stem cell function, nutrient sensing, age-related diseases
- MeSH terms
- Aging, Animals, Autophagy, Humans, Longevity, Mitochondria, Stem Cells, Signal Transduction, Cellular Senescence, Caloric Restriction, 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.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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