Department of Pathology, Albert Einstein College of Medicine, Bronx, NY, USA.
Biogerontology. 2012 Feb;13(1):21-35. doi: 10.1007/s10522-011-9331-x. Epub 2011 Apr 3.
Altered cellular homeostasis, accumulation of damaged non-functional organelles and presence of protein inclusions are characteristics shared by almost all types of differentiated cells in aged organisms. Cells rely on quality control mechanisms to prevent the occurrence of these events and the subsequent cellular compromise associated with them. What goes wrong in aging cells? Growing evidence supports gradual malfunctioning with age of the cellular quality control systems. In this review, we focus on autophagy, a catabolic process that contributes to the maintenance of cellular homeostasis through the degradation of unwanted and damaged components in lysosomes. We describe recent advances on the molecular characterization of this process, its different variants and the multiplicity of functions attributed to them. Autophagic dysfunction has been identified in severe human disorders, many of which worsen with age. We comment on the contribution of an adequate autophagic function to longevity, and the negative impact on health-span of the age-dependent decline in autophagic function.
细胞内环境稳态改变、受损无功能细胞器的积累以及蛋白包涵体的出现是衰老生物体内几乎所有类型分化细胞的共同特征。细胞依赖于质量控制机制来防止这些事件的发生以及随后与这些事件相关的细胞损伤。衰老细胞出了什么问题？越来越多的证据支持随着年龄的增长，细胞质量控制系统逐渐出现故障。在这篇综述中，我们专注于自噬，这是一种分解代谢过程，通过在溶酶体中降解不需要的和受损的成分来维持细胞内环境稳态。我们描述了这个过程的分子特征、不同变体以及归因于它们的多种功能的最新进展。自噬功能障碍已在严重的人类疾病中被识别，其中许多疾病随着年龄的增长而恶化。我们评论了适当的自噬功能对长寿的贡献，以及自噬功能随年龄下降对健康寿命的负面影响。
