Institute for Ageing and Health, Newcastle University, Campus for Ageing and Vitality, Newcastle upon Tyne, NE4 5PL, U.K.
Essays Biochem. 2013;55:119-31. doi: 10.1042/bse0550119.
Autophagy is a process of lysosome-dependent intracellular degradation that participates in the liberation of resources including amino acids and energy to maintain homoeostasis. Autophagy is particularly important in stress conditions such as nutrient starvation and any perturbation in the ability of the cell to activate or regulate autophagy can lead to cellular dysfunction and disease. An area of intense research interest is the role and indeed the fate of autophagy during cellular and organismal ageing. Age-related disorders are associated with increased cellular stress and assault including DNA damage, reduced energy availability, protein aggregation and accumulation of damaged organelles. A reduction in autophagy activity has been observed in a number of ageing models and its up-regulation via pharmacological and genetic methods can alleviate age-related pathologies. In particular, autophagy induction can enhance clearance of toxic intracellular waste associated with neurodegenerative diseases and has been comprehensively demonstrated to improve lifespan in yeast, worms, flies, rodents and primates. The situation, however, has been complicated by the identification that autophagy up-regulation can also occur during ageing. Indeed, in certain situations, reduced autophagosome induction may actually provide benefits to ageing cells. Future studies will undoubtedly improve our understanding of exactly how the multiple signals that are integrated to control appropriate autophagy activity change during ageing, what affect this has on autophagy and to what extent autophagy contributes to age-associated pathologies. Identification of mechanisms that influence a healthy lifespan is of economic, medical and social importance in our 'ageing' world.
自噬是一种溶酶体依赖性的细胞内降解过程，参与包括氨基酸和能量在内的资源的释放，以维持体内平衡。自噬在营养饥饿和细胞激活或调节自噬的能力受到任何干扰等应激条件下尤为重要，这可能导致细胞功能障碍和疾病。一个研究热点是自噬在细胞和机体衰老过程中的作用和命运。与衰老相关的疾病与增加的细胞应激和攻击有关，包括 DNA 损伤、能量供应减少、蛋白质聚集和受损细胞器的积累。在许多衰老模型中观察到自噬活性的降低，通过药理学和遗传学方法上调自噬可以缓解与年龄相关的病理学。特别是，自噬诱导可以增强与神经退行性疾病相关的有毒细胞内废物的清除，并且已经在酵母、蠕虫、苍蝇、啮齿动物和灵长类动物中全面证明可以延长寿命。然而，自噬上调也可能发生在衰老过程中，这一情况使情况变得复杂。事实上，在某些情况下，减少自噬体的诱导实际上可能对衰老细胞有益。未来的研究无疑将提高我们对控制适当自噬活性的多种信号在衰老过程中如何变化、这对自噬有什么影响以及自噬在多大程度上导致与年龄相关的病理学的理解。确定影响健康寿命的机制在我们这个“老龄化”的世界中具有经济、医学和社会意义。
