Differential role of melatonin in healthy brain aging: a systematic review and meta-analysis of the SAMP8 model

The relationship between oxidative stress (OS) and cellular senescence (CS) is an important research topic because of the rapidly aging global population. Melatonin (MT) is associated with aging and plays a pivotal role in redox homeostasis, but its role in maintaining physiological stability in the brain (especially in OS-induced senescence) remains elusive. Here, we systematically reviewed the differential role of MT on OS-induced senescence in the SAMP8 mouse model. Major electronic databases were searched for relevant studies. Pooled mean differences (MDs)/standardized mean differences (SMDs) with 95% confidence intervals (CIs) were calculated to estimate the effect size. Overall, 10 studies met the inclusion criteria. MT treatment was associated with the reduction of lipid peroxidation (SMD = −2.00, 95% CI [−2.91, −1.10]; p < 0.0001) and carbonylated protein (MD = −5.74, 95% CI [−11.03, –0.44]; p = 0.03), and with enhancement of the reduced-glutathione/oxidized-glutathione ratio (MD = 1.12, 95% CI [0.77, 1.47]; p < 0.00001). No differences were found in catalase and superoxide dismutase activities between MT-treated and vehicle-treated groups. Furthermore, nuclear-factor-κB, cyclin-dependent kinase-5, and p53 were regulated by MT administration. MT may improve physiological stability during aging by regulating interactions in brain senescence, but acts differentially on the antioxidant system.