衰老的分子和细胞机制原理。

Principles of the Molecular and Cellular Mechanisms of Aging.

机构信息

Medical Faculty, Institute for Genome Stability in Ageing and Disease, University of Cologne, Cologne, Germany; Cologne Cluster of Excellence in Cellular Stress Responses in Aging-Associated Diseases (CECAD) Research Center, University of Cologne, Cologne, Germany; Center for Molecular Medicine, University of Cologne, Cologne, Germany.

出版信息

J Invest Dermatol. 2021 Apr;141(4S):951-960. doi: 10.1016/j.jid.2020.11.018. Epub 2021 Jan 29.

DOI:10.1016/j.jid.2020.11.018

PMID:33518357

Abstract

Aging can be defined as a state of progressive functional decline accompanied by an increase in mortality. Time-dependent accumulation of cellular damage, namely lesions and mutations in the DNA and misfolded proteins, impair organellar and cellular function. Ensuing cell fate alterations lead to the accumulation of dysfunctional cells and hamper homeostatic processes, thus limiting regenerative potential; trigger low-grade inflammation; and alter intercellular and intertissue communication. The accumulation of molecular damage together with modifications in the epigenetic landscape, dysregulation of gene expression, and altered endocrine communication, drive the aging process and establish age as the main risk factor for age-associated diseases and multimorbidity.

摘要

衰老是指一种渐进性功能衰退的状态，伴随着死亡率的增加。随着时间的推移，细胞损伤的积累，即 DNA 中的损伤和突变以及错误折叠的蛋白质，会损害细胞器和细胞功能。随后的细胞命运改变导致功能失调细胞的积累，并阻碍体内平衡过程，从而限制了再生潜力；引发低度炎症；并改变细胞间和组织间的通讯。分子损伤的积累以及表观遗传景观的改变、基因表达的失调和内分泌通讯的改变，推动了衰老过程，并将年龄确立为与年龄相关的疾病和多种疾病的主要危险因素。