Normal mitochondrial function is a critical place in maintaining cellular homeostasis and normal physiological functions. The mitochondria are particularly sensitive to damage induced by reactive oxygen species (ROS) in the pathogenesis of disease and aging.

The aims of the present study were to characterize the mitochondrial dysfunction on liver of aging rats.

Compared with healthy young controls (4 month-old; n=10), aging rats (24 month-old; n=6) showed an increase of mitochondrial oxidative damage with a mitochondrial dysfunction characterized by depletion of membrane potential with increased proton leak and intramitochondrial free radical production, and a significant reduction of ATPase activity. In addition, mitochondrial respiration from untreated aging rats was Atr insensitive, showing that ANT was uncoupled, probably due to peroxidation of thiol groups. ANT has been shown to be one of the most sensitive places for pore opening. Consistent with these results, aging rats showed a significant overexpression of the active fragment of caspase 3 and caspase 9. All of these findings contribute to characterize better the mitochondrial dysfunction associated with aging in this experimental model in rats. Results in this study are in agreement with a significant amount of evidence that considers oxidative damage as one of the predominant mechanisms of cellular and tissular damage in aging. The ensuing oxidative stress leads to lipid peroxidation, mitochondrial dysfunction, and depletion of ATP causing tissular damage and physiological deficit.