Elucidating novel roles of selective autophagy in inflammation during ageing

全球60岁以上的人口在21世纪上半叶将增加三倍以上（达到近20亿人），到2050年将超过全球青年人口（15岁以下的人）的规模。英国有史以来第一次有1100万65岁或以上的人，而且领取养老金的人比16岁以下的儿童还多。人口老龄化给医疗保健和养老金制度带来巨大压力。因此，了解衰老的生物学是一项迫切需要的任务，以确保我们的人类社会有一个可行和可持续的未来。衰老细胞的表型特征之一是在没有任何明显感染的情况下发生慢性全身性炎症，这是老年人死亡的一个重要风险因素。我们发现，一种名为Kenny的蛋白质参与炎症的控制，通过一种称为自噬的细胞过程选择性降解。自噬，意思是“自我吞噬”，是一个重要的过程，涉及细胞质物质的降解。当条件变得不利时，细胞利用自噬产生物质和能量。它们还利用这一过程来清除受损的细胞成分或特定蛋白质，以便在细胞不需要时消除它们的功能。我们将使用果蝇Drosophila melanogaster作为遗传修饰的模式生物，以在分子水平上了解选择性自噬如何调节衰老过程中的炎症。这些机制在果蝇和人类之间非常相似，因此结果将直接关系到人类健康。该项目将为我们理解衰老过程中自噬和炎症的基本机制做出重大贡献，并可能用于旨在开发新策略的应用研究，以对抗与年龄相关的疾病并促进健康老龄化。

Global human population over the age of 60 will increase more than threefold (to nearly 2 billion individuals) during the first half of the twenty-first century, and that by 2050 it will exceed the size of the global population of young individuals (those individuals who are less than 15 years of age). For the first time in history, there are 11 million people aged 65 or over in the UK and also there are more pensioners than there are children under 16. Ageing population puts an enormous pressure on health care and pension system. Thus, understanding the biology of ageing is an urgently required task in order to ensure a viable and sustainable future for our human community.One of the phenotypic hallmarks of ageing cells is chronic, systemic inflammation in the absence of any apparent infection, and is a significant risk factor for mortality in the elderly. We discovered that a protein called Kenny, which participates in the control of inflammation, is selectively degraded by a cellular process called autophagy. Autophagy, which means 'self-eating', is an essential process that involves the degradation of cytoplasmic material. Cells use autophagy to generate materials and energy when conditions become unfavourable. They also use this process to clear damaged cellular components or specific proteins in order to abolish their function when it is not needed in the cell. We will use the fruit fly Drosophila melanogaster as a genetically modifiable model organism to understand at the molecular level how selective autophagy regulates inflammation during ageing. 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 and inflammation during ageing and could potentially be used in applied research aimed towards developing new strategies to fight age-related diseases and to promote healthy ageing.