Role of oxidative stress and protein oxidation in the aging process.
The hypothesis is that the rate of oxygen consumption and the ensuing accrual of molecular oxidative damage constitute a fundamental mechanism governing the rate of aging is supported by several lines of evidence: (i) life spans of cold blooded animals and mammals with unstable basal metabolic rate (BMR) are extended and oxidative damage (OxD) is attenuated by an experimental decrease in metabolic rate; (ii) single gene mutations in Drosophila and Caenorhabditis elegans that extend life span almost invariably result in a generalized slowing of physiological activities, albeit via different mechanisms, affecting a decrease in OxD; (iii) caloric restriction decreases body temperature and OxD; and, (iv) results of studies on the effects of transgenic overexpressions of antioxidant enzymes are generally supportive, but quite ambiguous. It is suggested that oxidative damage to proteins plays a crucial role in aging because oxidized proteins lose catalytic function and are preferentially hydrolyzed. It is hypothesized that oxidative damage to specific proteins constitutes one of the mechanisms linking oxidative stress/damage and age-associated losses in physiological functions.
Sohal
Rajindar S
RS
Department of Molecular Pharmacology and Toxicology, University of Southern California, Los Angeles, CA 90033, USA. sohal@usc.edu
D000375:Aging / Q000502:physiology*; D000818:Animals; D031204:Caloric Restriction; D005609:Free Radicals / Q000378:metabolism; D006801:Humans; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D010100:Oxygen / Q000378:metabolism; D011506:Proteins / Q000737:chemistry / Q000378:metabolism*; D017382:Reactive Oxygen Species
D005609:Free Radicals; D011506:Proteins; D017382:Reactive Oxygen Species; D010100:Oxygen