PMID- 35822019
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220928
IS  - 2673-6217 (Electronic)
IS  - 2673-6217 (Print)
IS  - 2673-6217 (Linking)
VI  - 2
DP  - 2021
TI  - The Multifaceted Role of Nutrient Sensing and mTORC1 Signaling in Physiology and 
      Aging.
PG  - 707372
LID - 10.3389/fragi.2021.707372 [doi]
LID - 707372
AB  - 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.
CI  - Copyright (c) 2021 Fernandes and Demetriades.
FAU - Fernandes, Stephanie A
AU  - Fernandes SA
AD  - Max Planck Institute for Biology of Ageing (MPI-AGE), Cologne, Germany.
AD  - Cologne Graduate School for Ageing Research (CGA), Cologne, Germany.
FAU - Demetriades, Constantinos
AU  - Demetriades C
AD  - Max Planck Institute for Biology of Ageing (MPI-AGE), Cologne, Germany.
AD  - Cologne Graduate School for Ageing Research (CGA), Cologne, Germany.
AD  - University of Cologne, Cologne Excellence Cluster on Cellular Stress Responses in 
      Aging-Associated Diseases (CECAD), Cologne, Germany.
LA  - eng
GR  - 757729/ERC_/European Research Council/International
PT  - Journal Article
PT  - Review
DEP - 20210827
PL  - Switzerland
TA  - Front Aging
JT  - Frontiers in aging
JID - 9918231199706676
PMC - PMC9261424
OTO - NOTNLM
OT  - aging
OT  - amino acids
OT  - dietary restriction
OT  - mTORC1
OT  - nutrient sensing
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2022/07/14 06:00
MHDA- 2022/07/14 06:01
PMCR- 2021/08/27
CRDT- 2022/07/13 02:11
PHST- 2021/05/09 00:00 [received]
PHST- 2021/08/12 00:00 [accepted]
PHST- 2022/07/13 02:11 [entrez]
PHST- 2022/07/14 06:00 [pubmed]
PHST- 2022/07/14 06:01 [medline]
PHST- 2021/08/27 00:00 [pmc-release]
AID - 707372 [pii]
AID - 10.3389/fragi.2021.707372 [doi]
PST - epublish
SO  - Front Aging. 2021 Aug 27;2:707372. doi: 10.3389/fragi.2021.707372. eCollection 
      2021.