Autophagy and the hallmarks of aging

被引:158
|
作者
Kaushik, Susmita [1 ,2 ]
Tasset, Inmaculada [1 ,2 ,3 ]
Arias, Esperanza [2 ,4 ]
Pampliega, Olatz [5 ]
Wong, Esther [6 ]
Martinez-Vicente, Marta [7 ]
Cuervo, Ana Maria [1 ,2 ,4 ]
机构
[1] Albert Einstein Coll Med, Dept Dev & Mol Biol, 1300 Morris Pk Ave, Bronx, NY 10461 USA
[2] Albert Einstein Coll Med, Inst Aging Studies, Bronx, NY 10461 USA
[3] Univ Cordoba, Dept Bioquim & Biol Mol, Cordoba, Spain
[4] Albert Einstein Coll Med, Marion Bessin Liver Res Ctr, Dept Med, Bronx, NY 10461 USA
[5] Univ Basque Country, Achucarro Basque Ctr Neurosci, Det Neurosciencias, UPV EHU, Leioa 48940, Spain
[6] Natl Univ Singapore, Natl Univ Hlth Syst, Hlth Longev Translat Res Programme, Yong Loo Lin Sch Med,Ctr Hlth Longev,Dept Physiol, Singapore, Singapore
[7] Vall dHebron Res Inst VHIR, Autophagy & Lysosomal Dysfunct Lab, Barcelona, Spain
基金
美国国家卫生研究院;
关键词
Aging; Chaperones; Lysosomes; Organelle turnover; Proteostasis; Proteolysis; CHAPERONE-MEDIATED AUTOPHAGY; LIFE-SPAN EXTENSION; UNFOLDED PROTEIN RESPONSE; DNA-DAMAGE RESPONSE; AGE-RELATED-CHANGES; MUSCLE STEM-CELLS; CAENORHABDITIS-ELEGANS; HEMATOPOIETIC STEM; OXIDATIVE STRESS; PIECEMEAL MICROAUTOPHAGY;
D O I
10.1016/j.arr.2021.101468
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Autophagy, an essential cellular process that mediates degradation of proteins and organelles in lysosomes, has been tightly linked to cellular quality control for its role as part of the proteostasis network. The current interest in identifying the cellular and molecular determinants of aging, has highlighted the important contribution of malfunctioning of autophagy with age to the loss of proteostasis that characterizes all old organisms. However, the diversity of cellular functions of the different types of autophagy and the often reciprocal interactions of autophagy with other determinants of aging, is placing autophagy at the center of the aging process. In this work, we summarize evidence for the contribution of autophagy to health-and lifespan and provide examples of the bidirectional interplay between autophagic pathways and several of the so-called hallmarks of aging. This central role of autophagy in aging, and the dependence on autophagy of many geroprotective interventions, has motivated a search for direct modulators of autophagy that could be used to slow aging and extend healthspan. Here, we review some of those ongoing therapeutic efforts and comment on the potential of targeting autophagy in aging.
引用
收藏
页数:20
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