The effect of melatonin administration on age-induced alterations in hepatocytes, central nervous system, immune
system, and skin are reviewed. Twenty-two-month-old Wistar rats and SAMP8 (senescence prone) mice of 10
months of age were used as experimental models. Wistar rats were analyzed untreated or after the chronic administration
of melatonin at a dose of 1 mg/kg/day in the drinking water for 10 weeks. At the end of the treatment period, the various
parameters were investigated. Results were compared with those of 2-month-old controls. In hepatocytes, aging induced a
significant increase in oxidative stress, inflammation, and apoptosis when compared to young animals. Melatonin administration
significantly ameliorated all these age-related changes.
The impairment of the cardiovascular system with aging appears to contribute to the increased morbidity and mortality of
the aged subjects. The process was investigated in SAMP8 mice of 10 months of age. Melatonin was provided for 30 days
at two different dosages (1 mg/kg/day and 10 mg/kg/day), also in the drinking water. After treatment, the expression of inflammatory
mediators (tumor necrosis factor-α, interleukin 1 and 10, NFκBp50 and NFκBp52), apoptosis markers (BAD,
BAX, and Bcl2), and parameters related to oxidative stress (heme oxygenases 1 and 2, endothelial and inducible nitric oxide
synthases) were determined in the heart. Inflammation as well as oxidative stress and apoptosis markers were increased
in old SAMP8 males, as compared to young controls. After treatment with melatonin, these age-altered parameters
were partially reversed. The results suggest that oxidative stress and inflammation increase with aging and that
chronic treatment with melatonin is able to reduce these parameters.
In the skin, a reduction of epidermal thickness together with a marked increase of the hypodermis with great fat accumulation
was observed in old rats, together with an increase in caspase 3, 8 of nucleosomes and LPO and a reduction in Bcl2
levels in the cultured keratinocytes. Melatonin treatment was able to reduce the fat content of the hypodermis and to increase
Bcl2 and reduce nucleosomes, caspases, and LPO in keratinocytes.
Conclusion: Melatonin administration exerts a beneficial effect against age-induced changes in several physiological parameters
in Wistar rats and SAMP 8 mice.