The aging ovary--the poor granulosa cells.

The development of a competent oocyte intimately depends on the maintenance of energetic homeostasis in the ovarian and follicular microenvironment. On this basis, it is very likely that the oocyte ages as the ovary ages. Starting from the molecular evidence for energy perturbations in the whole ovary, we review current knowledge on the involvement of endogenous highly reactive metabolites in follicle aging. The first part provides an update of recent findings that confirm the key role of oxidative stress in aged granulosa cells. The second part focuses on studies providing evidence for the implication of advanced glycation end product (AGE) in aging reproductive dysfunction. With their prolonged half-life and ability to act as signaling molecules AGEs may gradually accumulate in the ovary and potentiate the wide spatiotemporal spread of oxidative stress. Clinical evidence for this view supports the hypothesis that AGE is a good candidate as a predictive marker and therapeutic target in new strategies for improving reproductive counseling in aging women.