Search

The ageing of human populations has become a problem throughout the world. In this context, increasing the healthy lifespan of individuals has become an important target for medical research and governments. Cardiac disease remains the leading cause of morbidity and mortality in ageing populations and results in significant increases in healthcare costs. Although clinical and basic research have revealed many novel insights into the pathways that drive heart failure, the molecular mechanisms underlying cardiac ageing and age-related cardiac dysfunction are still not fully understood. In this review we summarize the most updated publications and discuss the central components that drive cardiac ageing. The following characters of mitochondria-related dysfunction have been identified during cardiac ageing: (a) disruption of the integrity of mitochondria-associated membrane (MAM) contact sites; (b) dysregulation of energy metabolism and dynamic flexibility; (c) dyshomeostasis of Ca2+ control; (d) disturbance to mitochondria–lysosomal crosstalk. Furthermore, Cisd2, a pro-longevity gene, is known to be mainly located in the endoplasmic reticulum (ER), mitochondria, and MAM. The expression level of Cisd2 decreases during cardiac ageing. Remarkably, a high level of Cisd2 delays cardiac ageing and ameliorates age-related cardiac dysfunction; this occurs by maintaining correct regulation of energy metabolism and allowing dynamic control of metabolic flexibility. Together, our previous studies and new evidence provided here highlight Cisd2 as a novel target for developing therapies to promote healthy ageing [ABSTRACT FROM AUTHOR]

In the ovary, the paracrine interactions between the oocyte and surrounded granulosa cells are critical for optimal oocyte quality and embryonic development. Mice lacking the androgen receptor (AR⁻/⁻) were noted to have reduced fertility with abnormal ovarian function that might involve the promotion of preantral follicle growth and prevention of follicular atresia. However, the detailed mechanism of how AR in granulosa cells exerts its effects on oocyte quality is poorly understood. Comparing in vitro maturation rate of oocytes, we found oocytes collected from AR⁻/⁻ mice have a significantly poor maturating rate with 60% reached metaphase II and 30% remained in germinal vesicle breakdown stage, whereas 95% of wild-type AR (AR⁺/⁺) oocytes had reached metaphase II. Interestingly, we found these AR⁻/⁻ female mice also had an increased frequency of morphological alterations in the mitochondria of granulosa cells with reduced ATP generation (0.18 ± 0.02 vs. 0.29 ± 0.02 µM/mg protein; p < 0.05) and aberrant mitochondrial biogenesis. Mechanism dissection found loss of AR led to a significant decrease in the expression of peroxisome proliferator-activated receptor γ (PPARγ) co-activator 1-β (PGC1-β) and its sequential downstream genes, nuclear respiratory factor 1 (NRF1) and mitochondrial transcription factor A (TFAM), in controlling mitochondrial biogenesis. These results indicate that AR may contribute to maintain oocyte quality and fertility via controlling the signals of PGC1-β-mediated mitochondrial biogenesis in granulosa cells.