Department of Developmental and Molecular Biology, Marion Bessin Liver Research Center, Institute for Aging Research, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Ageing Res Rev. 2011 Apr;10(2):205-15. doi: 10.1016/j.arr.2010.02.001. Epub 2010 Feb 10.
All cells count on precise mechanisms that regulate protein homeostasis to maintain a stable and functional proteome. A progressive deterioration in the ability of cells to preserve the stability of their proteome occurs with age and contributes to the functional loss characteristic of old organisms. Molecular chaperones and the proteolytic systems are responsible for this cellular quality control by assuring continuous renewal of intracellular proteins. When protein damage occurs, such as during cellular stress, the coordinated action of these cellular surveillance systems allows detection and repair of the damaged structures or, in many instances, leads to the complete elimination of the altered proteins from inside cells. Dysfunction of the quality control mechanisms and intracellular accumulation of abnormal proteins in the form of protein inclusions and aggregates occur in almost all tissues of an aged organism. Preservation or enhancement of the activity of these surveillance systems until late in life improves their resistance to stress and is sufficient to slow down aging. In this work, we review recent advances on our understanding of the contribution of chaperones and proteolytic systems to the maintenance of cellular homeostasis, the cellular response to stress and ultimately to longevity.
所有细胞都依赖于精确的机制来调节蛋白质稳态，以维持稳定和功能性的蛋白质组。随着年龄的增长，细胞维持蛋白质组稳定性的能力逐渐下降，导致老年生物体的功能丧失。分子伴侣和蛋白水解系统通过确保细胞内蛋白质的持续更新来负责这种细胞质量控制。当蛋白质受损时，例如在细胞应激期间，这些细胞监视系统的协调作用允许检测和修复受损结构，或者在许多情况下，导致从细胞内完全消除改变的蛋白质。在衰老生物体的几乎所有组织中，都存在质量控制机制功能障碍和以蛋白质包涵体和聚集体形式的异常蛋白质的细胞内积累。在生命后期保存或增强这些监视系统的活性可以提高它们对压力的抵抗力，足以减缓衰老。在这项工作中，我们回顾了最近对伴侣蛋白和蛋白水解系统对维持细胞内稳态、细胞对压力的反应以及最终对寿命的贡献的理解的进展。
