Cellular senescence and polycystic ovary syndrome: mechanisms and therapeutic strategies from a new perspective.

[OBJECTIVE] Cellular senescence is often linked to diseases or states of dysfunction, including reproductive disorders caused by ovarian dysfunction. It plays a significant role in conditions like polycystic ovary syndrome (PCOS). However, the specific effects and potential mechanisms of cellular senescence in PCOS need to be elucidated.

[METHODS] This review comprehensively consolidates evidence from original research articles and systematic reviews to explore the association between PCOS and cellular senescence, particularly emphasizing cell senescence markers and mechanisms linked to various PCOS phenotypes. In addition, it also covers potential mechanisms and advances in cellular senescence-related treatment methods in PCOS.

[RESULTS] Current evidence suggests that cellular senescence might contribute to PCOS through mechanisms such as replicative senescence, stress-induced premature senescence, and immunoinflammatory responses mediated by senescent cells. Key features of senescence, including cell cycle arrest, the senescence-associated secretory phenotype (SASP), epigenetic changes, abnormal cell morphology, oxidative stress, DNA damage from telomere shortening and telomerase inhibition, and overactivation of anti-apoptotic pathways, are all related to PCOS. These mechanisms might especially impair follicular development in obese, hyperandrogenic, or insulin-resistant patients with PCOS, leading to endometrial hyporeceptivity and increased pregnancy complications. Senolytic and senomorphic drugs are valuable clinical treatments for PCOS respectively targeted to immune surveillance mechanisms of senescent cells or mitigated the harmful effects of senescent cells on intercellular communication.

[CONCLUSIONS] There is a complex correlation mechanism between cellular senescence and PCOS. Studying these cellular senescence markers and mechanisms in PCOS could provide new insights into the pathogenesis, and lay the groundwork for in-depth study and potential application of anti-senescence therapies in treating PCOS.