Physical activity delays ovarian aging in part through adiponectin-related signaling pathways.

Ovarian aging leads to infertility, endocrine dysregulation and increased chronic disease risk, yet there are currently no approved therapies to delay ovarian aging. Physical activity (PA) is a crucial lifestyle factor for human health and antiaging, but its effects and mechanisms on ovarian aging remain unclear. Here we show, through a cross-sectional analysis of 152,435 participants in the UK Biobank, that lower PA levels were observed among postmenopausal persons when compared to premenopausal persons, and this finding was supported by another cross-sectional study of 12,418 participants in the National Health and Nutrition Examination Survey. Animal studies in mice show that higher levels of PA can delay ovarian aging. In addition, PA significantly increased adiponectin levels in the ovary, and the protective effects of PA on ovarian aging were attenuated in adiponectin-deficient mice. The adiponectin receptor agonist AdipoRon delayed ovarian aging and extended reproductive lifespan in mice. Our findings elucidate the role and mechanisms of PA in delaying ovarian aging, highlighting potential therapeutic targets for extending the reproductive lifespan.