Abstract
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.
Highlights
IntroductionThe female reproductive system is the first to show signs of physiological aging [1], with fertility decline and hormonal dysfunctions that can, in turn, affect overall health
Medical care advances and rising living standards have contributed to increasing lifespan, the age of menopause has remained constant at the age of ~50 years, leading women to live longer in suboptimal endocrine conditions [4]
The rate of 3- 4-mm follicles was higher in young ovaries, while a higher proportion of 5- 8-mm follicles was found in aged ovaries (Figure 1b)
Summary
The female reproductive system is the first to show signs of physiological aging [1], with fertility decline and hormonal dysfunctions that can, in turn, affect overall health. This leads to multiple medical and psychosocial problems, such as osteoporosis, cardiovascular disease, autoimmune disorders, and depression [2,3]. Medical care advances and rising living standards have contributed to increasing lifespan, the age of menopause has remained constant at the age of ~50 years, leading women to live longer in suboptimal endocrine conditions [4]. Reproductive aging has gradually become a key health issue and an adequate understanding of its mechanisms is essential in order to prevent age-related diseases and to promote health and longevity in women [5]
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