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REST/NRSF deficiency impairs autophagy and leads to cellular senescence in neurons
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 disorde...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8520714/ https://www.ncbi.nlm.nih.gov/pubmed/34520100 http://dx.doi.org/10.1111/acel.13471 |
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author | Rocchi, Anna Carminati, Emanuele De Fusco, Antonio Kowalska, Jagoda Aleksandra Floss, Thomas Benfenati, Fabio |
author_facet | Rocchi, Anna Carminati, Emanuele De Fusco, Antonio Kowalska, Jagoda Aleksandra Floss, Thomas Benfenati, Fabio |
author_sort | Rocchi, Anna |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-8520714 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-85207142021-10-25 REST/NRSF deficiency impairs autophagy and leads to cellular senescence in neurons Rocchi, Anna Carminati, Emanuele De Fusco, Antonio Kowalska, Jagoda Aleksandra Floss, Thomas Benfenati, Fabio Aging Cell Original Papers 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. John Wiley and Sons Inc. 2021-09-14 2021-10 /pmc/articles/PMC8520714/ /pubmed/34520100 http://dx.doi.org/10.1111/acel.13471 Text en © 2021 The Authors. Aging Cell published by Anatomical Society and John Wiley & Sons Ltd. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Papers Rocchi, Anna Carminati, Emanuele De Fusco, Antonio Kowalska, Jagoda Aleksandra Floss, Thomas Benfenati, Fabio REST/NRSF deficiency impairs autophagy and leads to cellular senescence in neurons |
title | REST/NRSF deficiency impairs autophagy and leads to cellular senescence in neurons |
title_full | REST/NRSF deficiency impairs autophagy and leads to cellular senescence in neurons |
title_fullStr | REST/NRSF deficiency impairs autophagy and leads to cellular senescence in neurons |
title_full_unstemmed | REST/NRSF deficiency impairs autophagy and leads to cellular senescence in neurons |
title_short | REST/NRSF deficiency impairs autophagy and leads to cellular senescence in neurons |
title_sort | rest/nrsf deficiency impairs autophagy and leads to cellular senescence in neurons |
topic | Original Papers |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8520714/ https://www.ncbi.nlm.nih.gov/pubmed/34520100 http://dx.doi.org/10.1111/acel.13471 |
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