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mTOR at the nexus of nutrition, growth, ageing and disease
Open accessAbstract
The mTOR pathway integrates a diverse set of environmental cues, such as growth factor signals and nutritional status, to direct eukaryotic cell growth. Over the past two and a half decades, mapping of the mTOR signalling landscape has revealed that mTOR controls biomass accumulation and metabolism by modulating key cellular processes, including protein synthesis and autophagy. Given the pathway's central role in maintaining cellular and physiological homeostasis, dysregulation of mTOR signalling has been implicated in metabolic disorders, neurodegeneration, cancer and ageing. In this Review, we highlight recent advances in our understanding of the complex regulation of the mTOR pathway and discuss its function in the context of physiology, human disease and pharmacological intervention.
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“a notable feature of effective anti-aging interventions, such as lowered insulin/IGF-1 signaling 296 and disruption of the TORC1 complex 296,297 , is the diverse mechanisms by which they target different aging hallmarks in different tissues to maintain healthspan of the whole organism.”
From Hallmarks of aging: An expanding universe (2023) · cites this paper as [296]
In the citing paper
“Conversely, during protein breakdown, the amino acids released by lysosome and proteasome directly stimulate mTOR5 and therefore, protein synthesis might increase during muscle atrophy.”
From Mechanisms of muscle atrophy and hypertrophy: implications in health and disease (2021) · cites this paper as [5]
In the citing paper
“This kinase integrates multiple stimuli coming not only from hormones but also from cytokines, nutrients, ATP/AMP ratio, and signals to the translation machinery via p70S6K1, which controls the ribosomal protein S6, and factor 4E binding protein 1 (4EBP1), which negatively regulates the ribosomal eukaryotic translation initiator factor 4E5.”
From Mechanisms of muscle atrophy and hypertrophy: implications in health and disease (2021) · cites this paper as [5]
In the citing paper
“While mTORC2 is related to glucose and lipids homeostasis5, mTORC1 regulates several anabolic processes, including protein synthesis, ribosome, and mitochondria biogenesis.”
From Mechanisms of muscle atrophy and hypertrophy: implications in health and disease (2021) · cites this paper as [5]
In the citing paper
“Amino acids, especially the branched ones, are well-known growth-promoting agents because they directly stimulate mTOR5.”
From Mechanisms of muscle atrophy and hypertrophy: implications in health and disease (2021) · cites this paper as [5]
In the citing paper
“The mTOR kinase is part of the multiprotein complexes mTORC1 and mTORC2, which participate in the sensing of high amino acid concentrations and regulate multiple aspects of anabolic metabolism.219”
From Meta-hallmarks of aging and cancer (2023) · cites this paper as [219]
In the citing paper
“Hamartin (encoded by TSC1)–tuberin (encoded by TSC2) complexes negatively regulate mTORC1 by inhibiting GTP binding protein RHEB”
From Autophagy in kidney homeostasis and disease (2020) · cites this paper as [15]
In the citing paper
“mTORC1 is a master regulator of autophagy that is activated by amino acids or growth factors, such as insulin and insulin-like growth factor-1”
From Autophagy in kidney homeostasis and disease (2020) · cites this paper as [15]
In the citing paper
“Under nutrient-rich conditions, active mTORC1 suppresses autophagy by phosphorylating ULK1 and ATG13 to inhibit the ULK1–ULK2 complex.”
From Autophagy in kidney homeostasis and disease (2020) · cites this paper as [15]
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Metadata
- Authors
- Liu, G. Y., & Sabatini, D. M.
- Affiliations
- Broad Institute (US)
- Corresponding author
- Sabatini, David M.
- Venue
- Nature Reviews Molecular Cell Biology
- Published
- 2020-01-14
- Volume
- 21
- Issue
- 4
- Pages
- 183-203
- ISSN
- 1471-0072 (ISSN-L)
- 1471-0080
- PMC
- PMC7102936
- OpenAlex
- W2999421965
- Cited by
- 2,737
- References
- 287
- Citations by year
- 2026: 356 · 2025: 469 · 2024: 462 · 2023: 447 · 2022: 436 · 2021: 412 · 2020: 152
- FWCI
- 34.98
- Type
- journal article
- Language
- en
- Update notices
- correction (2020-01-31)
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Nature Reviews Molecular Cell Biology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion, cc-by-nc-sa)
- Funders
- National Cancer Institute (R01CA103866, R01CA129105, F31CA232340)
- National Institute of General Medical Sciences (T32GM007287)
- National Institute of Allergy and Infectious Diseases (R37AI047389)
- Topics
- 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
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Keywords
- mTOR signaling, nutrient sensing, cell growth, protein synthesis, autophagy, metabolic homeostasis, aging, neurodegeneration, cancer, metabolic disorders
- MeSH terms
- Aging, Animals, Autophagy, Humans, Metabolic Diseases, Neoplasms, Nutritional Status, Protein Biosynthesis, Signal Transduction, TOR Serine-Threonine Kinases
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