The emerging role of the melatonin-cortisol axis: Bridging aging-related biomarkers to environment-driven aging research

The aging process is predominantly influenced by genetic and environmental factors. Environmental factors that accelerate biological aging, known as gerontogens, increase organismal vulnerability and susceptibility to disease, thereby elevating the risks of multiple aging-related disease onset and mortality. However, there is a notable deficiency in effective biomarkers for predicting aging-related phenotypes accelerated by gerontogens. Melatonin and cortisol serve as markers of the circadian system and are hormones that undergo significant alterations during the aging process. Imbalances in the melatonin-cortisol axis are closely linked to this aging process. This review summarizes the mediating effects and underlying mechanisms of melatonin-cortisol axis in gerontogen-induced aging, and discusses the feasibility of melatonin and cortisol as biomarkers for predicting aging-related phenotypes induced by gerontogens. This review evaluates the application value of melatonin and cortisol as biomarkers for the screening and risk assessment of potential gerontogens, as well as the intervention research of aging-related phenotypes induced by gerontogens.