Molecular Mechanisms of Autophagy Decline during Aging

被引:4
作者
Lim, Shaun H. Y. [1 ,2 ]
Hansen, Malene [2 ,3 ]
Kumsta, Caroline [2 ]
机构
[1] Sanford Burnham Prebys Med Discovery Inst, Grad Sch Biomed Sci, 10901 North Torrey Pines Rd, La Jolla, CA 92037 USA
[2] Sanford Burnham Prebys Med Discovery Inst, Program Dev Aging & Regenerat, 10901 North Torrey Pines Rd, La Jolla, CA 92037 USA
[3] Buck Inst Res Aging, 8001 Redwood Blvd, Novato, CA 94945 USA
关键词
aging; autophagy; proteostasis; lysosomes; proteolysis; LIFE-SPAN; NORDIHYDROGUAIARETIC ACID; MITOCHONDRIAL INTEGRITY; AGE; ATG9; LONGEVITY; DISEASE; GENES; BRAIN; PHOSPHORYLATION;
D O I
10.3390/cells13161364
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Macroautophagy (hereafter autophagy) is a cellular recycling process that degrades cytoplasmic components, such as protein aggregates and mitochondria, and is associated with longevity and health in multiple organisms. While mounting evidence supports that autophagy declines with age, the underlying molecular mechanisms remain unclear. Since autophagy is a complex, multistep process, orchestrated by more than 40 autophagy-related proteins with tissue-specific expression patterns and context-dependent regulation, it is challenging to determine how autophagy fails with age. In this review, we describe the individual steps of the autophagy process and summarize the age-dependent molecular changes reported to occur in specific steps of the pathway that could impact autophagy. Moreover, we describe how genetic manipulations of autophagy-related genes can affect lifespan and healthspan through studies in model organisms and age-related disease models. Understanding the age-related changes in each step of the autophagy process may prove useful in developing approaches to prevent autophagy decline and help combat a number of age-related diseases with dysregulated autophagy.
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页数:16
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