Aging is associated with increased lipid peroxidation in human hearts, butnot with mitochondrial respiratory chain enzyme defects

Background: Aging is associated with increased oxidative damage at multiple cellular and tissular levels. A decrease in mitochondrial function has rep eatedly been advocated as a primary key event, especially on the basis of a nalysis of skeletal muscle mitochondria. However, some doubts on this issue have arisen when confounding variables (such as physical activity or smoki ng habit) have been taken into account in the analysis of mitochondrial res piratory chain (MRC) enzyme activities or when additional analytical parame ters such as enzyme ratios have been considered. Objective: To determine wh ether oxidative damage and enzyme activities of the MRC are influenced by t he aging process in human hearts. Patients and methods: We studied cardiac muscle obtained from 59 organ donors (age: 56+/-12 years, 75% men). Oxidati ve membrane damage was evaluated through the assessment of lipid peroxidati on. Absolute and relative enzyme activities (AEA and REA, respectively) of complex I, II, III and TV of the MRC were spectrophotometrically measured. Stoichiometric relationships among MRC complexes were also assessed through calculating MRC ratios. Linear regression analyses were employed to disclo se any potential correlation between mitochondrial dysfunction and aging. R esults: We found a progressive, significant increase of heart membrane Lipi d peroxidation with aging (P<0.05). Conversely, neither AEA nor REA decreas ed with age (P=n.s. for all complexes). Similarly to observations in other tissues, we found that stoichiometry of the MRC enzymes is maintained withi n a narrow range in human hearts. When the effects of aging on MRC ratios w ere explored, we failed again in demonstrating any subtle disarray. Conclus ion: MRC enzymes remain preserved in heart with aging, and thus they cannot be considered the main cause of the increased oxidative damage associated with aging. (C) 2000 Elsevier Science B.V. All rights reserved.