Pennarossa Georgia, De Iorio Teresina, Gandolfi Fulvio, Brevini Tiziana A L
Laboratory of Biomedical Embryology, Department of Health, Animal Science and Food Safety and Center for Stem Cell Research, Università degli Studi di Milano, 20133 Milan, Italy.
Laboratory of Biomedical Embryology, Department of Agricultural and Environmental Sciences-Production, Landscape, Agroenergy, Università degli Studi di Milano, 20133 Milan, Italy.
Nanomaterials (Basel). 2022 Jan 21;12(3):345. doi: 10.3390/nano12030345.
Advances in medical care, improvements in sanitation, and rising living standards contribute to increased life expectancy. Although this reflects positive human development, it also poses new challenges. Among these, reproductive aging is gradually becoming a key health issue because the age of menopause has remained constant at ~50 years, leading women to live longer in suboptimal endocrine conditions. An adequate understanding of ovarian senescence mechanisms is essential to prevent age-related diseases and to promote wellbeing, health, and longevity in women. We here analyze the impact of aging on the ovarian extracellular matrix (ECM), and we demonstrate significant changes in its composition and organization with collagen, glycosaminoglycans, and laminins significantly incremented, and elastin, as well as fibronectin, decreased. This is accompanied by a dynamic response in gene expression levels of the main ECM- and protease-related genes, indicating a direct impact of aging on the transcription machinery. Furthermore, in order to study the mechanisms driving aging and identify possible strategies to counteract ovarian tissue degeneration, we here described the successful production of a 3D ECM-based biological scaffold that preserves the structural modifications taking place in vivo and that represents a powerful high predictive in vitro model for reproductive aging and its prevention.
医疗保健的进步、卫生条件的改善以及生活水平的提高有助于延长预期寿命。尽管这反映了积极的人类发展，但也带来了新的挑战。其中，生殖衰老正逐渐成为一个关键的健康问题，因为绝经年龄一直保持在约50岁，导致女性在次优内分泌条件下活得更长。充分了解卵巢衰老机制对于预防与年龄相关的疾病以及促进女性的健康、幸福和长寿至关重要。我们在此分析衰老对卵巢细胞外基质（ECM）的影响，并证明其组成和组织结构发生了显著变化，胶原蛋白、糖胺聚糖和层粘连蛋白显著增加，而弹性蛋白以及纤连蛋白减少。这伴随着主要ECM和蛋白酶相关基因表达水平的动态反应，表明衰老对转录机制有直接影响。此外，为了研究驱动衰老的机制并确定对抗卵巢组织退化的可能策略，我们在此描述了一种基于3D ECM的生物支架的成功制备，该支架保留了体内发生的结构变化，并且是用于生殖衰老及其预防的强大的高预测性体外模型。
