Protein oxidation in aging and age-related diseases.
Although different theories have been proposed to explain the aging process, it is generally agreed that there is a correlation between aging and the accumulation of oxidatively damaged proteins, lipids, and nucleic acids. Oxidatively modified proteins have been shown to increase as a function of age. Studies reveal an age-related increase in the level of protein carbonyl content, oxidized methionine, protein hydrophobicity, and cross-linked and glycated proteins as well as the accumulation of less active enzymes that are more susceptible to heat inactivation and proteolytic degredation. Factors that decelerate protein oxidation also increase the life span of animals and vice versa. Furthermore, a number of age-related diseases have been shown to be associated with elevated levels of oxidatively modified proteins. The chemistry of reactive oxygen species-mediated protein modification will be discussed. The accumulation of oxidatively modified proteins may reflect deficiencies in one or more parameters of a complex function that maintains a delicate balance between the presence of a multiplicity of prooxidants, antioxidants, and repair, replacement, or elimination of biologically damaged proteins.
Stadtman
E R
ER
Laboratory of Biochemistry, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892-0342, USA. erstadtman@nih.gov
D000375:Aging / Q000378:metabolism*; D000596:Amino Acids / Q000737:chemistry*; D000818:Animals; D000975:Antioxidants / Q000378:metabolism / Q000494:pharmacology; D017209:Apoptosis; D003432:Cross-Linking Reagents / Q000009:adverse effects; D003545:Cysteine / Q000737:chemistry; D004194:Disease / Q000209:etiology*; D006801:Humans; D008136:Longevity / Q000502:physiology; D008715:Methionine / Q000737:chemistry; D008954:Models, Biological; D009569:Nitric Oxide / Q000378:metabolism; D016877:Oxidants / Q000009:adverse effects / Q000378:metabolism; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D010455:Peptides / Q000737:chemistry / Q000528:radiation effects; D030421:Peroxynitrous Acid / Q000009:adverse effects / Q000378:metabolism; D011489:Protein Denaturation; D011506:Proteins / Q000737:chemistry* / Q000528:radiation effects; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D014443:Tyrosine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000378:metabolism
D000596:Amino Acids; D000975:Antioxidants; D003432:Cross-Linking Reagents; D016877:Oxidants; D010455:Peptides; D011506:Proteins; D017382:Reactive Oxygen Species; D030421:Peroxynitrous Acid; D009569:Nitric Oxide; C002744:3-nitrotyrosine; D014443:Tyrosine; D008715:Methionine; D003545:Cysteine