PMID- 35860029
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220722
IS  - 1663-9812 (Print)
IS  - 1663-9812 (Electronic)
IS  - 1663-9812 (Linking)
VI  - 13
DP  - 2022
TI  - Glutamine Availability Regulates the Development of Aging Mediated by mTOR 
      Signaling and Autophagy.
PG  - 924081
LID - 10.3389/fphar.2022.924081 [doi]
LID - 924081
AB  - Glutamine is a conditionally essential amino acid involved in energy production 
      and redox homeostasis. Aging is commonly characterized by energy generation 
      reduction and redox homeostasis dysfunction. Various aging-related diseases have 
      been reported to be accompanied by glutamine exhaustion. Glutamine 
      supplementation has been used as a nutritional therapy for patients and the 
      elderly, although the mechanism by which glutamine availability affects aging 
      remains elusive. Here, we show that chronic glutamine deprivation induces 
      senescence in fibroblasts and aging in Drosophila melanogaster, while glutamine 
      supplementation protects against oxidative stress-induced cellular senescence and 
      rescues the D-galactose-prompted progeria phenotype in mice. Intriguingly, we 
      found that long-term glutamine deprivation activates the Akt-mTOR pathway, 
      together with the suppression of autolysosome function. However, the inhibition 
      of the Akt-mTOR pathway effectively rescued the autophagy impairment and cellular 
      senescence caused by glutamine deprivation. Collectively, our study demonstrates 
      a novel interplay between glutamine availability and the aging process. 
      Mechanistically, long-term glutamine deprivation could evoke mammalian target of 
      rapamycin (mTOR) pathway activation and autophagy impairment. These findings 
      provide new insights into the connection between glutamine availability and the 
      aging process.
CI  - Copyright (c) 2022 Zhou, Chen, Du, Tai, Han, Huang, Wang, Gong, Yang and Xiao.
FAU - Zhou, Jiao
AU  - Zhou J
AD  - Department of Geriatrics, State Key Laboratory of Biotherapy, West China 
      Hospital, Sichuan University, Chengdu, China.
FAU - Chen, Honghan
AU  - Chen H
AD  - Department of Geriatrics, State Key Laboratory of Biotherapy, West China 
      Hospital, Sichuan University, Chengdu, China.
FAU - Du, Jintao
AU  - Du J
AD  - Department of Otorhinolaryngology Head and Neck Surgery, West China Hospital, 
      Sichuan University, Chengdu, China.
FAU - Tai, Haoran
AU  - Tai H
AD  - Department of Geriatrics, State Key Laboratory of Biotherapy, West China 
      Hospital, Sichuan University, Chengdu, China.
AD  - Development and Regeneration Key Laboratory of Sichuan Province, Department of 
      Anatomy and Histology and Embryology, Chengdu Medical College, Chengdu, China.
FAU - Han, Xiaojuan
AU  - Han X
AD  - Department of Geriatrics, State Key Laboratory of Biotherapy, West China 
      Hospital, Sichuan University, Chengdu, China.
FAU - Huang, Ning
AU  - Huang N
AD  - Department of Geriatrics, State Key Laboratory of Biotherapy, West China 
      Hospital, Sichuan University, Chengdu, China.
FAU - Wang, Xiaobo
AU  - Wang X
AD  - Department of Geriatrics, State Key Laboratory of Biotherapy, West China 
      Hospital, Sichuan University, Chengdu, China.
FAU - Gong, Hui
AU  - Gong H
AD  - Department of Geriatrics, State Key Laboratory of Biotherapy, West China 
      Hospital, Sichuan University, Chengdu, China.
FAU - Yang, Mingyao
AU  - Yang M
AD  - Institute of Animal Genetics and Breeding, Sichuan Agricultural University, 
      Chengdu, China.
FAU - Xiao, Hengyi
AU  - Xiao H
AD  - Department of Geriatrics, State Key Laboratory of Biotherapy, West China 
      Hospital, Sichuan University, Chengdu, China.
LA  - eng
PT  - Journal Article
DEP - 20220704
PL  - Switzerland
TA  - Front Pharmacol
JT  - Frontiers in pharmacology
JID - 101548923
PMC - PMC9289448
OTO - NOTNLM
OT  - aging
OT  - autophagy
OT  - cellular senescence
OT  - glutamine
OT  - mTOR
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- 2022/07/22 06:00
MHDA- 2022/07/22 06:01
PMCR- 2022/07/04
CRDT- 2022/07/21 02:24
PHST- 2022/04/20 00:00 [received]
PHST- 2022/06/17 00:00 [accepted]
PHST- 2022/07/21 02:24 [entrez]
PHST- 2022/07/22 06:00 [pubmed]
PHST- 2022/07/22 06:01 [medline]
PHST- 2022/07/04 00:00 [pmc-release]
AID - 924081 [pii]
AID - 10.3389/fphar.2022.924081 [doi]
PST - epublish
SO  - Front Pharmacol. 2022 Jul 4;13:924081. doi: 10.3389/fphar.2022.924081. 
      eCollection 2022.