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mTOR is a key modulator of ageing and age-related disease
Open accessAbstract
Many experts in the biology of ageing believe that pharmacological interventions to slow ageing are a matter of 'when' rather than 'if'. A leading target for such interventions is the nutrient response pathway defined by the mechanistic target of rapamycin (mTOR). Inhibition of this pathway extends lifespan in model organisms and confers protection against a growing list of age-related pathologies. Characterized inhibitors of this pathway are already clinically approved, and others are under development. Although adverse side effects currently preclude use in otherwise healthy individuals, drugs that target the mTOR pathway could one day become widely used to slow ageing and reduce age-related pathologies in humans.
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“the mammalian target of rapamycin (mTOR) pathway, which is induced by amino acids, growth factors, and RT, is often inhibited during CR, and mediates CR-induced health benefits in model organisms [37].”
From Resistance Training Prevents Muscle Loss Induced by Caloric Restriction in Obese Elderly Individuals: A Systematic Review and Meta-Analysis (2018) · cites this paper as [37]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“a well-known inhibitor of mTOR, rapamycin, inhibits the production of SASP factors”
From The role of cellular senescence and SASP in tumour microenvironment (2023) · cites this paper as [121]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
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“which might explain its beneficial impact on longevity [121,122].”
From The role of cellular senescence and SASP in tumour microenvironment (2023) · cites this paper as [121]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Genetic down-regulation of mTORC1 activity in yeast, worms and flies extends longevity and attenuates further longevity benefits from DR, suggesting that mTOR inhibition phenocopies DR”
From The Hallmarks of Aging (2013) · cites this paper as Johnson et al., 2013
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In the citing paper
“Inhibition of mTOR has been shown to extend lifespan and to improve the function of ageing organ systems, including the immune system, in multiple preclinical species.18, 19”
From Targeting the biology of ageing with mTOR inhibitors to improve immune function in older adults: phase 2b and phase 3 randomised trials (2021) · cites this paper as [18]
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In the citing paper
“One of the best validated mechanisms underlying ageing biology is the activity of the protein kinase mTOR.”
From Targeting the biology of ageing with mTOR inhibitors to improve immune function in older adults: phase 2b and phase 3 randomised trials (2021) · cites this paper as [18]
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“More importantly, these pathways have been evaluated in mammalian models, in which health span and lifespan have been extended by genetic manipulation or drugs (Johnson et al., 2013).”
From Metformin as a tool to target aging (2016) · cites this paper as Johnson et al., 2013
In the citing paper
“Of significance is that metformin, like rapamycin, is known to inhibit mTOR signaling, and the inhibition of the mTOR signaling pathway with rapamycin has been shown to extend lifespan in C. elegans, S. cerevisiae, and Drosophila melanogaster (fruit fly) (221–225).”
From A Critical Review of the Evidence That Metformin Is a Putative Anti-Aging Drug That Enhances Healthspan and Extends Lifespan (2021) · cites this paper as [224]
In the citing paper
“Of significance is that metformin, like rapamycin, is known to inhibit mTOR signaling, and the inhibition of the mTOR signaling pathway with rapamycin has been shown to extend lifespan in C. elegans, S. cerevisiae, and Drosophila melanogaster (fruit fly) (221–225).”
From A Critical Review of the Evidence That Metformin Is a Putative Anti-Aging Drug That Enhances Healthspan and Extends Lifespan (2021) · cites this paper as [224]
In the citing paper
“Based on previous studies in the aging field, it is believed that Nrf2 is repressed by mTOR pathway (downstream target); therefore, an inhibition of mTOR by rapamycin would increase the activity of Nrf2 (Johnson et al., 2013).”
From Rapamycin inhibits the secretory phenotype of senescent cells by a Nrf2-independent mechanism (2017) · cites this paper as Johnson et al., 2013
In the citing paper
“The benefits of nicotinamide riboside can be suppressed by treatment of mice with inhibitors of either SIRT1 or mTOR complex 1 (mTORC1), which is paradoxical as inhibition of mTORC1 signalling normally extends healthspan and lifespan220.”
From Ageing and rejuvenation of tissue stem cells and their niches (2023) · cites this paper as [220]
In the citing paper
“The benefits of nicotinamide riboside can be suppressed by treatment of mice with inhibitors of either SIRT1 or mTOR complex 1 (mTORC1), which is paradoxical as inhibition of mTORC1 signalling normally extends healthspan and lifespan220.”
From Ageing and rejuvenation of tissue stem cells and their niches (2023) · cites this paper as [220]
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Citations
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“…good example of this is the mechanistic target of rapamycin (mTOR) pathway that was first genetically implicated in aging in yeast (Fabrizio et al. 2001) and has since emerged as an important target for delaying aging in multicellular invertebrates and mice (Johnson et al. 2013a, 2015).”
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“Additionally, it has been found that 4E-BP1, a target of mTORC1, is also regulated by FOXO in fruit flies (Johnson et al., 2013; Mannick & Lamming, 2023).”
BackgroundInfluentialPostbiotics: A Promising Approach to Combat Age-Related Diseases
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“…mTORC1 The mTOR pathway is a central regulator of cell growth, prolifration and metabolism and has been implicated in multiple ageelated diseases ( Johnson et al., 2013 ). mTOR is a serine/threonine inase that co-ordinates numerous cellular processes and assemles into two distinct multiprotein…”
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“Moreover, mTOR complex activation suppresses lipolysis and autophagy (the degradative signals often likened to cellular homeostasis maintenance) (Johnson et al., 2013; Saxton and Sabatini, 2017) (Table 6).”
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“There is increasing evidence that signaling through the phosphoinositide-3-kinase (PI3K)-AKT-mammalian target of rapamycin (mTOR) pathway is of critical importance in cellular senescence and aging [13].”
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“As far as we know, mTOR is currently the only known pharmacological target which has been shown to delay ageing (Johnson et al., 2013).”
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Sestrins are Gatekeepers in the Way from Stress to Aging and Disease
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Metadata
- Authors
- Johnson, S. C., Rabinovitch, P. S., & Kaeberlein, M.
- Affiliations
- University of Washington (US)
- Guangdong Medical College (CN)
- Corresponding author
- Kaeberlein, Matt
- Venue
- Nature
- Published
- 2013-01-16
- Volume
- 493
- Issue
- 7432
- Pages
- 338-345
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC3687363
- OpenAlex
- W2010583480
- Cited by
- 1,676
- References
- 100
- Citations by year
- 2026: 87 · 2025: 82 · 2024: 117 · 2023: 121 · 2022: 113 · 2021: 164 · 2020: 136 · 2019: 140 · 2018: 125 · 2017: 133 · 2016: 136 · 2015: 119 · 2014: 131 · 2013: 72
- FWCI
- 9.38
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- National Institutes of Health
- National Institute on Aging (R01AG031108, T32AG000057, P01AG001751, R01AG039390, R01AG038550, P30AG013280)
- 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
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Autophagy in Disease and Therapy
- Keywords
- mTOR, aging, age-related diseases, lifespan extension, rapamycin, mTOR inhibitors, pharmacological interventions
- MeSH terms
- Aging, Animals, Humans, Insulin, Insulin-Like Growth Factor I, Longevity, Signal Transduction, TOR Serine-Threonine Kinases
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