REST/NRSF deficiency impairs autophagy and leads to cellular senescence in neurons
| Autor: | Fabio Benfenati, Thomas Floss, Jagoda Aleksandra Kowalska, Anna Rocchi, Emanuele Carminati, Antonio De Fusco |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Senescence
Aging Programmed cell death autophagy Autophagy Mitochondria Neurons Oxidative Stress Rapamycin Rest/nrsf Trehalose senescence mitochondria neurons oxidative stress rapamycin REST/NRSF trehalose Animals Cellular Senescence Humans Mice Repressor Proteins Biology Mitochondrion medicine.disease_cause medicine Transcription factor Original Paper Cell Biology Original Papers Cell biology Proteostasis Physiological Aging Oxidative stress |
| Zdroj: | Aging Cell Aging Cell, DOI: 10.1111/acel.13471:e13471 (2021) |
| ISSN: | 1474-9726 1474-9718 |
| DOI: | 10.1111/acel.13471:e13471 |
| Popis: | 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. Cellular senescence is one of the aging drivers and a key feature of a variety of human age‐related disorders. The transcriptional repressor REST deficiency leads to cellular senescence in primary neurons. Rest depletion causes DNA damage, impairment of autophagic flux, mitochondrial dysfunction, and alteration of SASP genes expression. We describe a novel transcriptional regulator of the senescence program. |
| Databáze: | OpenAIRE |
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