Aims: 

The exact cellular and molecular mechanisms of the aging process are unclear, but there is growing evidence, that age-related changes are consequences of oxidative stress. It has been suggested that mitochondria are one of major sources of free radicals and also an important target for their damaging effects. Recent studies have suggested that hydroxynonenal (HNE), is an important mediator of cellular damage associated with oxidative stress. Therefore, in the present study we examined the effect of HNE on cytochrome c oxidase (COX) activity, oxidative modifications of mitochondrial lipids and proteins in rat heart.

Methods: 

For experiments were used hearts from rats of three age categories 6, 15 and 26-month old. Fluorescence studies were performed as reported Kaplan et al. (2000). HNE and malondialdehyde were measured according to standard kits. COX activity was measured spectrophotometrically.

Results: 

The activity of COX was 44.6 ± 1.6% (p < 0.001) loss in senescent hearts, whereas the COX I protein level was unchanged. Lipid peroxidation in mitochondrial membranes was increased progressively with age. Activity of COX was inhibited, with concomitant increase in endogenous HNE level. Compared to adult rats, there was significant increase in protein dityrosines, lysine conjugates and decrease in sulfhydryl groups content.

Conclusion: 

Our results suggest that loss of COX activity during aging may be due in part to oxidative modifications of mitochondrial proteins and/or lipids. We propose that mitochondrial dysfunction increases in age-dependent manner and is mediated, in part, by modification of specific mitochondrial proteins by the lipid peroxidation product HNE.