A novel component of protein aggregates regulates fertility and ageing

现代医学的进步大大延长了人类的预期寿命。其后果是与老龄化有关的疾病和与老龄化有关的生殖功能障碍的频率增加。父母们年龄越来越大，这种趋势在未来可能会更加频繁。因此，了解生殖系统衰老的生物学是一项迫切需要的任务，以确保我们人类社会有一个可行和可持续的未来。细胞老化的标志之一是细胞内蛋白质聚集体的积累。最近的研究表明，细胞中主要的蛋白质分解细胞机制之一的崩溃，即自噬，与衰老相关疾病的发展有关。自噬是一种重要的分解代谢过程，涉及细胞物质的降解。当条件变得不利时，细胞利用自噬来产生材料和能量。他们也使用这一过程来清除受损的细胞成分。我们发现一种名为UbcD4的蛋白质通过自噬选择性地降解并在自噬突变体的雄性生殖系统中积累。我们还发现UbcD4突变体的雄性寿命缩短。因此，我们假设UbcD4通过自噬调节机制维持健康寿命。我们将以果蝇黑腹果蝇作为可遗传修饰的模式生物，在分子水平上了解选择性自噬如何调节衰老和生殖。这些机制在果蝇和人类之间非常相似，因此结果将与人类健康直接相关。该项目将对我们理解生殖和衰老过程中自噬的基本机制作出重大贡献，并有可能用于旨在制定防治与年龄有关的疾病和促进健康老龄化的新战略的应用研究。

Advances in modern medicine have led to a significant increase in human life expectancy. A consequence of this has been the increase of the frequency of ageing-related diseases and ageing-related reproductive dysfunction. Parents are becoming older and this trent is likely to be more frequent in the future. Thus, understanding the biology of ageing of the reproductive systems is an urgently required task in order to ensure a viable and sustainable future for our human community. One of the hallmarks of ageing cells is the intracellular accumulation of protein aggregates. Recent studies have indicated that a breakdown of one of the major proteolytic cellular machineries in cells, namely autophagy, is involved in the development of ageing-related diseases. Autophagy is an essential catabolic process that involves the degradation of cellular material. Cells use autophagy to generate materials and energy when conditions become unfavourable. They also use this process to clear damaged cellular components. We discovered that a protein called UbcD4 is selectively degraded by autophagy and accumulates in male reproductive system of autophagy mutants We also found that UbcD4 mutant males show reduced lifespan. Therefore, we hypothesize that UbcD4 maintains healthy lifespan through an autophagy-regulated mechanism.We will use the fruit fly Drosophila melanogaster as a genetically modifiable model organism to understand at the molecular level how selective autophagy regulates ageing and reproduction. These mechanisms are very similar between fruit flies and humans, so the results will have direct relevance to human health. This project will make a major contribution to our understanding of the fundamental mechanisms of autophagy during reproduction and ageing and could potentially be used in applied research aimed towards developing new strategies to fight age-related diseases and to promote healthy ageing.