Mitochondrial alterations, cellular response to oxidative stress and defective degradation of proteins in aging.
Respiratory function decline and increase of oxidative stress in mitochondria have been proposed as important contributors to human aging. A wide spectrum of alterations in aged individuals and senescent cells are similar and are correlated to cellular response to sublethal dose of oxidative stress. These alterations and responses include: (1) decline in mitochondrial respiratory function; (2) increase in the rate of production of reactive oxygen species (ROS); (3) accumulation of mitochondrial DNA (mtDNA) mutations; (4) increase in the levels of oxidative damage to DNA, protein, and lipids; and (5) decrease in the capacities of degradation of oxidatively damaged proteins and other macromolecules. Responses to oxidative stress and their subsequent interactions in tissues result in the deleterious effect of ROS on the cellular function, which culminate in aging and degenerative diseases. In this review, we focus on the roles that ROS play in age-related oxidative damage to mtDNA and proteins and oxidative stress responses at the molecular and cellular levels. The alterations of gene expression profiles elicited by oxidative stress in aging animals are discussed. We suggest that the increase in mitochondrial production of ROS and decline in the cellular capacity to cope with oxidative stress and subsequent accumulation of mtDNA mutations and oxidized proteins play an important role in the aging process.
Lee
H C
HC
Department of Biochemistry, National Yang-Ming University, Taipei, Taiwan, Republic of China. joeman@ym.edu.tw
Wei
Y H
YH
D000375:Aging / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D000818:Animals; D015870:Gene Expression; D006801:Humans; D046911:Macromolecular Substances; D008928:Mitochondria / Q000378:metabolism* / Q000502:physiology; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D011506:Proteins / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism
D046911:Macromolecular Substances; D011506:Proteins; D017382:Reactive Oxygen Species