Verbeke P, Clark B F, Rattan S I
Danish Centre for Molecular Gerontology, Laboratory of Cellular Ageing, Department of Molecular and Structural Biology, University of Aarhus, Gustav Wieds Vej 10-C, DK-8000, Aarhus, Denmark.
Exp Gerontol. 2000 Sep;35(6-7):787-94. doi: 10.1016/s0531-5565(00)00143-1.
Intracellular and extracellular proteins are subject to a variety of spontaneous non-enzymatic modifications which affect their structure, function and stability. Protein oxidation and glycation are tightly linked and are implicated in the development of many pathological consequences of aging. Although multiple endogenous pathways in the cell can prevent the formation of oxidized and glycated proteins, and repair and degrade abnormal proteins, such abnormal proteins do accumulate during aging. The heat shock response involving the family of stress-proteins or the so-called heat shock proteins (HSP), represents the quickest and highly conserved response to proteotoxic insults. Since repeated mild heat stress is able to prevent the onset of various age-related changes during cellular aging in vitro, we suggest that treatments which increase HSP expression should reduce the extent of accumulation of abnormal proteins during aging. Such modulation of aging is an example of hormesis, which is characterized by the beneficial effects resulting from the cellular responses to mild repeated stress.
细胞内和细胞外蛋白质会经历各种自发的非酶修饰，这些修饰会影响其结构、功能和稳定性。蛋白质氧化和糖基化紧密相连，并与衰老的许多病理后果的发展有关。尽管细胞内的多种内源性途径可以阻止氧化和糖基化蛋白质的形成，并修复和降解异常蛋白质，但这些异常蛋白质在衰老过程中确实会积累。涉及应激蛋白家族或所谓热休克蛋白（HSP）的热休克反应，是对蛋白质毒性损伤最快且高度保守的反应。由于反复轻度热应激能够在体外细胞衰老过程中预防各种与年龄相关变化的发生，我们认为增加HSP表达的治疗方法应能减少衰老过程中异常蛋白质的积累程度。这种对衰老的调节是应激效应的一个例子，其特征是细胞对轻度反复应激的反应产生有益效果。
