Menopause transition timing reflects systemic biological aging

Earlier menopause has been associated with reduced lifespan and increased disease risk, but whether menopause itself accelerates aging or reflects an underlying faster biological aging trajectory remains unresolved. Here, we combined animal models of menopausal transition with epigenetic analyses in postmenopausal women, to investigate this relationship.

In rats, neither surgically induced menopause nor natural reproductive senescence resulted in increased epigenetic age acceleration. In women, accelerated epigenetic aging was observed only in individuals who reached postmenopause earlier than the cohort median, independent of metabolic health status. Differential methylation analysis suggested an association between age at menopause and pathways involved in longevity, chromatin regulation, and neurodegeneration.