Identification of Nine Melatonin-Associated Genes on Aging Through Circadian Rhythm Regulation in Human and Mouse Brain

Abstract

Sleep is essential for physiological homeostasis, and chronic sleep deprivation accelerates aging, including in the brain. Melatonin, secreted by the pineal gland, decreases with age due to reduced activity of AANAT, a key enzyme in its synthesis. Melatonin modulates the cAMP signaling pathway, influencing sleep-wake cycles and circadian rhythm stability. This study investigates the impact of melatonin-related genes on aging by regulating circadian rhythm. We identified 188 differentially expressed genes (DEGs) in brain tissues from a melatonin-deficient mouse model, selecting four genes related to circadian rhythm and aging through KEGG analysis. Additionally, in human brain tissues, 1,339 age-related genes were identified, among which five genes were involved in circadian regulation. There were no overlapping genes between the two analyses, leading us to consider all nine genes as influencers of aging through circadian rhythm regulation. These findings provide foundational data for anti-aging strategies using melatonin.