Melatonin protects against age-related DNA damage in the brains of female senescence-accelerated mice

We investigated whether melatonin reduces the age-related susceptibility of brain to oxidative DNA damage. Brain tissues and blood samples were obtain ed in the middle of dark period of the daily light:dark cycle from female s enescence-accelerated mice (SAM-P/6) at ages 4, 8, and 12 months. Serum mel atonin concentrations and the contents of deoxyguanosine (dG) and 8-hydroxy deoxyguanosine (8-OHdG) in DNA extracted from these brain homogenates were measured by high-performance liquid chromatography, Contents of 8-OHdG show ed a significant age-related increase (P < 0.001), while that of dG did not . The 8-OHdG:dG ratio also exhibited a significant age-related increase (P < 0.001). Serum melatonin concentration decreased markedly between 8 (159.7 +/- 4.5 pg/mL) and 12 (46.8 +/- 4.5 pg/mL) months of age (P < 0.0001). Ora l melatonin. administration (2 mu g/mL in water) starting at 8 months of ag e, which produced a significant increase in serum. melatonin concentration at 12 months (187.6 +/- 18.3 pg/mL) compared with untreated animals (P < 0. 0001), also resulted in significant decreases in brain 8-OHdG contents and 8-OHdG:dG ratios. These results indicate that administration of a physiolog ic dose of melatonin to SAM-P/6 mice may prevent the age-related oxidative DNA damage in the brain.