Improved mitochondrial function and increased life span after chronic melatonin treatment in senescent prone mice

We investigated whether chronic melatonin administration influences mitochondrial oxidative stress and life span in mice. Diaphragmatic mitochondria from female senescent prone (SAMP8) and senescent resistant (SAMRI) mice at 5 and 10 months of age were studied. Mitochondrial oxidative stress was determined by measuring the levels of lipid peroxiclation, glutathione and glutathione disulficle, and glutathione peroxiclase and reductase activities. Mitochondrial function was assessed by measuring the activity of the respiratory chain complexes and the ATP content. The results suggest that the age-dependent rnitochondrial oxidative damage in the diaphragm of SAMP8 mice was accompanied by a reduction in the electron transport chain complex activities and in ATP levels. Furthermore, nielatonin administration between I and 10 months of age normalized the redox and the bioenergetic status of the mitochondria and increased the ATP levels. Melatonin also increased both half-life and longevity, mainly in SAMP8 group. These results suggest an age-related increase in mitochondria vulnerability to oxidation in SAM mice at 10 months of age that was counteracted by rnelatonin therapy. The effects of melatonin on mitochondrial physiology probably underline the ability of the indolearnine to increase maximal life span in these animals. (c) 2008 Elsevier Inc. All rights reserved.