Open AccessREST/NRSF deficiency impairs autophagy and leads to cellular senescence in neurons
Author(s) -
Rocchi Anna,
Carminati Emanuele,
De Fusco Antonio,
Kowalska Jagoda Aleksandra,
Floss Thomas,
Benfenati Fabio
Publication year - 2021
Publication title -
aging cell
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.103
H-Index - 140
eISSN - 1474-9726
pISSN - 1474-9718
DOI - 10.1111/acel.13471
Subject(s) - proteostasis , senescence , biology , autophagy , rest (music) , gene silencing , oxidative stress , microbiology and biotechnology , phenotype , transcription factor , programmed cell death , repressor , longevity , cellular senescence , neuroscience , genetics , endocrinology , medicine , gene , apoptosis
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.