REST/NRSF deficiency impairs autophagy and leads to cellular senescence in neurons.
REST/NRSF
autophagy
mitochondria
neurons
oxidative stress
rapamycin
senescence
trehalose
Journal
Aging cell
ISSN: 1474-9726
Titre abrégé: Aging Cell
Pays: England
ID NLM: 101130839
Informations de publication
Date de publication:
10 2021
10 2021
Historique:
revised:
14
07
2021
received:
24
08
2020
accepted:
05
08
2021
pubmed:
15
9
2021
medline:
19
2
2022
entrez:
14
9
2021
Statut:
ppublish
Résumé
During aging, brain performances decline. Cellular senescence is one of the aging drivers and a key feature of a variety of human age-related disorders. The transcriptional repressor RE1-silencing transcription factor (REST) has been associated with aging and higher risk of neurodegenerative disorders. However, how REST contributes to the senescence program and functional impairment remains largely unknown. Here, we report that REST is essential to prevent the senescence phenotype in primary mouse neurons. REST deficiency causes failure of autophagy and loss of proteostasis, increased oxidative stress, and higher rate of cell death. Re-establishment of autophagy reverses the main hallmarks of senescence. Our data indicate that REST has a protective role in physiological aging by regulating the autophagic flux and the senescence program in neurons, with implications for neurological disorders associated with aging.
Identifiants
pubmed: 34520100
doi: 10.1111/acel.13471
pmc: PMC8520714
doi:
Substances chimiques
RE1-silencing transcription factor
0
Repressor Proteins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e13471Commentaires et corrections
Type : ErratumIn
Informations de copyright
© 2021 The Authors. Aging Cell published by Anatomical Society and John Wiley & Sons Ltd.
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