REST/NRSF deficiency impairs autophagy and leads to cellular senescence in neurons.

ABSTRACT: 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

SUBMITTER: Rocchi A 

PROVIDER: S-EPMC8520714 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature