Therapeutic Aspects of Melatonin-sirtuin Crosstalk: An Updated Review of Current Data Based on Cellular Mechanisms

Melatonin, a master regulator of circadian rhythms and diverse physiological processes, exhibits complex interactions with various molecules. Sirtuins, a family of histone deacetylases, are key players in aging, stress responses, and metabolism and represent a critical target for melatonin. This review explores the multifaceted functions of melatonin and sirtuins, delving into the molecular mechanisms of their interaction. We further examine the impact of this synergy on various pathologies across different organs. Studies suggest that melatonin modulates SIRT1 and SIRT3 signaling pathways, offering protection in neurodegenerative, cardiovascular, skeletal, and pulmonary diseases, as well as renal and hepatic dysfunction. Additionally, melatonin-sirtuin interactions have been implicated in mitigating cancer development and promoting health in the female and male reproductive systems. Notably, the majority of studies across these systems demonstrate melatonin's ability to regulate SIRT1 and SIRT3 signaling, thereby alleviating associated pathologies. In conclusion, the intricate interplay between melatonin and, particularly, SIRT1 and SIRT3 emerges as a crucial modulator of diverse signaling pathways, with promising therapeutic implications for a wide range of diseases.