Aims: 

Increasing evidence supports the participation of melatonin in the organism defense against oxidative stress. Thus, we investigated whether chronic melatonin administration prevents mitochondrial oxidative stress and affects life span in mice.

Methods: 

Brain mitochondria from female senescent prone (SAMP8) and resistant (SAMR1) mice at 5 and 10 months of age were studied. Mitochondrial oxidative stress was determined by the levels of lipid peroxidation, glutathione and glutathione disulfide, and glutathione peroxidase and reductase activities. Mitochondrial function was assessed by the activity of the respiratory chain complexes and the ATP content.

Results: 

Chronic melatonin administration to SAMP8 mice prevented the age-dependent brain mitochondrial oxidative stress and the bioenergetic failure, increasing the ATP production. Melatonin administration also counteracted the age-dependent increase in circulating pro-inflammatory cytokines such as TNFa and INFg, and nitric oxide levels. Melatonin increased both half-life and longevity by 25%, mainly in SAMP8 group.

Conclusions: 

These results suggest an age-related increase in brain mitochondria vulnerability to oxidation in SAM mice at 10 months of age that was counteracted by melatonin therapy. The effects of melatonin on mitochondrial physiology probably underline the ability of the indoleamine to increase maximal life span in these animals.

Supported in part by grants: RD06/0013/0008 (RETICEF) and CTS-101