Teppa-Garrán Alejandro, Pérez-Peña Efraín, Sobrevia Luis, Marín Reinaldo
Policlínica Metropolitana, Calle A-1, Urb. Caurimare, Caracas 1061, Venezuela.
Institute of Sciences in Human Reproduction "Vida", Guadalajara, Mexico.
Biochim Biophys Acta Mol Basis Dis. 2025 Jul 17:167987. doi: 10.1016/j.bbadis.2025.167987.
Ovarian aging is a major determinant of female reproductive longevity, characterized by declining oocyte quality and reduced ovarian reserve. With more women delaying childbearing, age-related infertility has become an urgent biomedical concern. Mitochondrial dysfunction plays a central role in this process, leading to oxidative damage and metabolic disturbances that impair oocyte competence. These alterations are linked to poorer outcomes in assisted reproductive technology (ART), particularly for women over 35, who face significantly reduced success rates. This review examines the key mechanisms of ovarian aging, including oxidative stress, DNA damage, telomere shortening, and mitochondrial dysfunction, all contributing to diminished oocyte quality and quantity. Special focus is given to sirtuins, especially SIRT1 and SIRT3, as critical regulators of redox balance in oocytes and granulosa cells. The review also addresses the impact of age-related changes on chromosomal cohesion and ovarian fibrosis. Importantly, mitochondrial insufficiency is increasingly recognized as a factor in broader age-related diseases, such as metabolic disorders and cancer, suggesting shared molecular pathways between reproductive aging and systemic health. Recent advances highlight the potential of targeted nutrient supplementation to modulate redox homeostasis, enhance sirtuin activity, and preserve mitochondrial function-strategies that may benefit both ovarian health and overall aging. This intersection of reproductive biology and mitochondrial medicine is driving interest in pharmacologic interventions to improve oocyte quality and mitigate age-related comorbidities.
卵巢衰老为女性生殖寿命的主要决定因素，其特征是卵母细胞质量下降和卵巢储备减少。随着越来越多的女性推迟生育，与年龄相关的不孕症已成为一个紧迫的生物医学问题。线粒体功能障碍在此过程中起核心作用，导致氧化损伤和代谢紊乱，损害卵母细胞功能。这些改变与辅助生殖技术（ART）的较差结果相关，尤其是对于35岁以上的女性，她们面临着显著降低的成功率。本综述探讨了卵巢衰老的关键机制，包括氧化应激、DNA损伤、端粒缩短和线粒体功能障碍，所有这些都导致卵母细胞质量和数量下降。特别关注了去乙酰化酶，尤其是SIRT1和SIRT3，它们是卵母细胞和颗粒细胞氧化还原平衡的关键调节因子。该综述还讨论了与年龄相关的变化对染色体凝聚和卵巢纤维化的影响。重要的是，线粒体功能不全越来越被认为是更广泛的与年龄相关疾病（如代谢紊乱和癌症）的一个因素，这表明生殖衰老和全身健康之间存在共同的分子途径。最近的进展突出了靶向营养补充剂调节氧化还原稳态、增强去乙酰化酶活性和维持线粒体功能的潜力，这些策略可能有益于卵巢健康和整体衰老。生殖生物学和线粒体医学的这种交叉引发了人们对药物干预的兴趣，以改善卵母细胞质量并减轻与年龄相关的合并症。
