Circadian rhythm homeostasis biomarkers: current landscape and emerging frontiers

Circadian rhythm homeostasis refers to the endogenous 24-hour variations that govern biological activities and coordinate physiological processes by integrating hormonal, metabolic, and immune systems to facilitate organismal adaptation to environmental periodicity. The system orchestrates behavioral patterns and physiological rhythms, and its disruption has been implicated in diverse pathologies. Current methods for circadian rhythm assessment include measurement of melatonin levels, sleep diaries, chronotype analysis, rest–activity rhythms, and core body temperature monitoring. Several biomarkers, including hormones, key metabolites, and neurochemical regulators, are also associated with circadian rhythms. In this review, we aim to synthesize the current research on circadian biomarkers, including sample sources, detection methods, classifications, and evolving frontiers. Identifying and validating these biomarkers (e.g. melatonin and glucocorticoids) hold significant promise for advancing precision medicine in circadian rhythm-related disorders, thereby enabling targeted prevention and therapy.