REST/NRSF deficiency impairs autophagy and leads to cellular senescence in neurons.
REST/NRSF deficiency impairs autophagy and leads to cellular senescence in neurons.
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DOI：
10.1111/acel.13471
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发表时间：
2021-10
期刊：
影响因子：
7.8
通讯作者：
Benfenati F
中科院分区：
文献类型：
--
作者：
Rocchi A;Carminati E;De Fusco A;Kowalska JA;Floss T;Benfenati F
在衰老过程中，大脑的表现会下降。细胞衰老是衰老的驱动因素之一，也是多种人类衰老相关疾病的重要特征。转录抑制因子Re1沉默转录因子(REST)与衰老和神经退行性疾病的高风险有关。然而，休息对衰老程序和功能损害的作用在很大程度上仍不清楚。在这里，我们报告REST对于防止原代小鼠神经元的衰老表型是必不可少的。休息不足会导致自噬失败和蛋白平衡丧失，氧化应激增加，细胞死亡率更高。自噬的重新建立逆转了衰老的主要特征。我们的数据表明，REST通过调节神经元中的自噬通量和衰老程序，在生理衰老中起到保护作用，这可能与衰老相关的神经疾病有关。细胞衰老是衰老的驱动因素之一，也是多种人类衰老相关疾病的重要特征。转录抑制因子REST缺陷导致原代神经元细胞衰老。静息耗竭导致DNA损伤、自噬通量受损、线粒体功能障碍和SASP基因表达改变。我们描述了一种新的衰老程序的转录调节因子。
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.
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影响因子：
64.5
作者：
López-Otín C;Blasco MA;Partridge L;Serrano M;Kroemer G
通讯作者：
Kroemer G
DOI：
10.15252/embj.201592862
发表时间：
2016-04-01
期刊：
The EMBO journal
影响因子：
--
作者：
Correia-Melo C;Marques FD;Anderson R;Hewitt G;Hewitt R;Cole J;Carroll BM;Miwa S;Birch J;Merz A;Rushton MD;Charles M;Jurk D;Tait SW;Czapiewski R;Greaves L;Nelson G;Bohlooly-Y M;Rodriguez-Cuenca S;Vidal-Puig A;Mann D;Saretzki G;Quarato G;Green DR;Adams PD;von Zglinicki T;Korolchuk VI;Passos JF
通讯作者：
Passos JF
影响因子：
8.8
作者：
Meyer, Katharina;Feldman, Heather M.;Yankner, Bruce A.
通讯作者：
Yankner, Bruce A.
影响因子：
5.1
作者：
Pecoraro-Bisogni, F.;Lignani, Gabriele;Baldelli, Pietro
通讯作者：
Baldelli, Pietro
影响因子：
11.4
作者：
Pozzi, Davide;Lignani, Gabriele;Baldelli, Pietro
通讯作者：
Baldelli, Pietro