Rhythms of life: melatonin, nutrition, sleep, and antioxidant strategies for healthy aging

Circadian rhythms orchestrate nearly all physiological and behavioral functions, and their deterioration with aging contributes to sleep disruption, cognitive decline, and increased vulnerability to disease. Melatonin, the primary hormonal signal of darkness, plays a central role in maintaining circadian synchrony, regulating sleep, and exerting antioxidant and neuroprotective effects. This review provides an integrative synthesis of current evidence on the multi-layered role of melatonin in aging, encompassing molecular, neurobiological, behavioral, and nutritional dimensions. Aging alters the circadian system, particularly melatonin secretion, amplitude, and receptor sensitivity, and these changes affect sleep architecture, metabolism, and cognitive function. Melatonin depicts pleiotropic actions as a circadian synchronizer, sleep facilitator, mitochondrial protector, immunomodulator, and neuroprotective agent. Evidence suggests that age-related melatonin decline contributes to "accelerated" aging through increased oxidative stress, mitochondrial dysfunction, and inflammatory burden ("inflammaging"), whereas restoring melatonin levels, via supplementation or diet, may mitigate such processes. In parallel, we address the emerging field of chrononutrition, emphasizing that the timing of food intake and consumption of melatonin-rich or polyphenol-containing foods can enhance circadian rhythmicity, improve sleep quality, and reduce age-related metabolic and oxidative stress. Melatonin decline represents both a biomarker and mediator of circadian aging. Integrating chronobiological and nutritional interventions, including timed melatonin supplementation, dietary chronobiotics, and lifestyle alignment with the light-dark cycle, holds promise for preserving circadian integrity, delaying physiological aging, and extending health span. Forthcoming research should focus on personalized chronotherapy and nutritional chronobiology to better harness melatonin's therapeutic potential in aging populations.