title: Effects of age and caloric restriction on mitochondrial protein oxidative damage in mice.
abstract: The hypothesis that life-span extension by caloric restriction (CR) is contingent upon the attenuation of macromolecular oxidative damage was tested in two different strains of mice: the C57BL/6, whose life span is extended by CR, and the DBA/2, in which CR has relatively minor or no impact on longevity. Mice were fed ad libitum (AL) or restricted to 40% lesser food, starting at 4 months of age. Protein damage was measured as protein-linked adducts of 4-hydroxy-2-nonenal (HNE) and malondialdehyde (MDA) in skeletal muscle mitochondria at 6 and 23 months of age. Protein-HNE and -MDA content increased with age in C57BL/6 mice and CR significantly attenuated these augmentations. Metalloprotease 1, NADP-dependent mitochondrial malic enzyme (isoform 2) and citrate synthase were identified by mass spectroscopy to contain HNE/MDA adducts. DBA/2 mice exhibited little effect of age or CR on protein HNE/MDA content in skeletal muscle mitochondria. In contrast, protein-HNE levels in liver mitochondria showed a significant increase with age in AL-fed mice of both strains, and CR caused significant attenuation of this damage. Overall, results indicated that the age-related increase in protein oxidative damage and its abatement by CR are genotype- and tissue-specific, and not a universal phenomenon.
authors.affiliation: Department of Pharmacology and Pharmaceutical Sciences, University of Southern California, 1985 Zonal Avenue, Los Angeles, CA 90089, United States.
authors.forename: Xiao-Dong
authors.initials: XD
authors.lastname: Li
authors.forename: Igor
authors.initials: I
authors.lastname: Rebrin
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Forster
authors.forename: Rajindar S
authors.initials: RS
authors.lastname: Sohal
mesh_terms: D000375:Aging / Q000378:metabolism*; D000818:Animals; D031204:Caloric Restriction; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D051379:Mice; D008811:Mice, Inbred DBA; D008931:Mitochondria, Muscle / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism*; D018384:Oxidative Stress
chemical_list: D024101:Mitochondrial Proteins; D008315:Malondialdehyde