Beyond Chronological Age: Circadian Disruption, Mitochondrial Dysfunction, and the Biology of Female Reproductive Aging

Female reproductive aging involves progressive follicular depletion, declining oocyte competence, and changes in reproductive endocrine function. This narrative review examines the potential interactions between circadian regulation, mitochondrial dysfunction, and oxidative stress in ovarian aging. Evidence on sleep timing, shift work, ovarian clock genes, mitochondrial bioenergetics, and redox homeostasis is considered. Although these processes share pathways involved in cellular metabolism and stress regulation, direct evidence that circadian disruption accelerates ovarian reserve depletion or shortens reproductive lifespan in humans remains limited. The proposed circadian–mitochondrial relationship should therefore be considered a testable hypothesis rather than an established causal pathway. Longitudinal human studies integrating objective circadian measures, ovarian reserve markers, mitochondrial assessments, and reproductive outcomes are needed to clarify these interactions and their clinical significance.