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The Multifaceted Role of Nutrient Sensing and mTORC1 Signaling in Physiology and Aging

The mechanistic Target of Rapamycin (mTOR) is a growth-related kinase that, in the context of the mTOR complex 1 (mTORC1), touches upon most fundamental cellular processes. Consequently, its activity is a critical determinant for cellular and organismal physiology, while its dysregulation is commonl...

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Autores principales: Fernandes, Stephanie A., Demetriades, Constantinos
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9261424/
https://www.ncbi.nlm.nih.gov/pubmed/35822019
http://dx.doi.org/10.3389/fragi.2021.707372
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author Fernandes, Stephanie A.
Demetriades, Constantinos
author_facet Fernandes, Stephanie A.
Demetriades, Constantinos
author_sort Fernandes, Stephanie A.
collection PubMed
description The mechanistic Target of Rapamycin (mTOR) is a growth-related kinase that, in the context of the mTOR complex 1 (mTORC1), touches upon most fundamental cellular processes. Consequently, its activity is a critical determinant for cellular and organismal physiology, while its dysregulation is commonly linked to human aging and age-related disease. Presumably the most important stimulus that regulates mTORC1 activity is nutrient sufficiency, whereby amino acids play a predominant role. In fact, mTORC1 functions as a molecular sensor for amino acids, linking the cellular demand to the nutritional supply. Notably, dietary restriction (DR), a nutritional regimen that has been shown to extend lifespan and improve healthspan in a broad spectrum of organisms, works via limiting nutrient uptake and changes in mTORC1 activity. Furthermore, pharmacological inhibition of mTORC1, using rapamycin or its analogs (rapalogs), can mimic the pro-longevity effects of DR. Conversely, nutritional amino acid overload has been tightly linked to aging and diseases, such as cancer, type 2 diabetes and obesity. Similar effects can also be recapitulated by mutations in upstream mTORC1 regulators, thus establishing a tight connection between mTORC1 signaling and aging. Although the role of growth factor signaling upstream of mTORC1 in aging has been investigated extensively, the involvement of signaling components participating in the nutrient sensing branch is less well understood. In this review, we provide a comprehensive overview of the molecular and cellular mechanisms that signal nutrient availability to mTORC1, and summarize the role that nutrients, nutrient sensors, and other components of the nutrient sensing machinery play in cellular and organismal aging.
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spelling pubmed-92614242022-07-11 The Multifaceted Role of Nutrient Sensing and mTORC1 Signaling in Physiology and Aging Fernandes, Stephanie A. Demetriades, Constantinos Front Aging Aging The mechanistic Target of Rapamycin (mTOR) is a growth-related kinase that, in the context of the mTOR complex 1 (mTORC1), touches upon most fundamental cellular processes. Consequently, its activity is a critical determinant for cellular and organismal physiology, while its dysregulation is commonly linked to human aging and age-related disease. Presumably the most important stimulus that regulates mTORC1 activity is nutrient sufficiency, whereby amino acids play a predominant role. In fact, mTORC1 functions as a molecular sensor for amino acids, linking the cellular demand to the nutritional supply. Notably, dietary restriction (DR), a nutritional regimen that has been shown to extend lifespan and improve healthspan in a broad spectrum of organisms, works via limiting nutrient uptake and changes in mTORC1 activity. Furthermore, pharmacological inhibition of mTORC1, using rapamycin or its analogs (rapalogs), can mimic the pro-longevity effects of DR. Conversely, nutritional amino acid overload has been tightly linked to aging and diseases, such as cancer, type 2 diabetes and obesity. Similar effects can also be recapitulated by mutations in upstream mTORC1 regulators, thus establishing a tight connection between mTORC1 signaling and aging. Although the role of growth factor signaling upstream of mTORC1 in aging has been investigated extensively, the involvement of signaling components participating in the nutrient sensing branch is less well understood. In this review, we provide a comprehensive overview of the molecular and cellular mechanisms that signal nutrient availability to mTORC1, and summarize the role that nutrients, nutrient sensors, and other components of the nutrient sensing machinery play in cellular and organismal aging. Frontiers Media S.A. 2021-08-27 /pmc/articles/PMC9261424/ /pubmed/35822019 http://dx.doi.org/10.3389/fragi.2021.707372 Text en Copyright © 2021 Fernandes and Demetriades. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Aging
Fernandes, Stephanie A.
Demetriades, Constantinos
The Multifaceted Role of Nutrient Sensing and mTORC1 Signaling in Physiology and Aging
title The Multifaceted Role of Nutrient Sensing and mTORC1 Signaling in Physiology and Aging
title_full The Multifaceted Role of Nutrient Sensing and mTORC1 Signaling in Physiology and Aging
title_fullStr The Multifaceted Role of Nutrient Sensing and mTORC1 Signaling in Physiology and Aging
title_full_unstemmed The Multifaceted Role of Nutrient Sensing and mTORC1 Signaling in Physiology and Aging
title_short The Multifaceted Role of Nutrient Sensing and mTORC1 Signaling in Physiology and Aging
title_sort multifaceted role of nutrient sensing and mtorc1 signaling in physiology and aging
topic Aging
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9261424/
https://www.ncbi.nlm.nih.gov/pubmed/35822019
http://dx.doi.org/10.3389/fragi.2021.707372
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