Accumulation of altered proteins and ageing: Causes and effects
Accumulation of altered proteins and ageing: Causes and effects
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DOI：
10.1016/j.exger.2006.03.004
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发表时间：
2006-05-01
影响因子：
3.9
通讯作者：
Hipkiss, Alan R.
中科院分区：
文献类型：
--
作者：
Hipkiss, Alan R.
改变蛋白质的积累是衰老最常见的分子症状。蛋白质的改变也与许多与年龄相关的病症有关。改变的蛋白质不断产生，但通常会被细胞蛋白酶选择性降解；它们在衰老过程中的积累可以通过产量增加或消除减少之一或两者来解释。蛋白质改变的来源包括细胞质和线粒体核糖体的错误合成、不稳定氨基酸残基的自发脱酰胺、异构化和外消旋化、活性氧和氮物种造成的损伤以及葡萄糖和更具反应性的代谢物引起的糖化和交联。糖化蛋白可能会损伤线粒体，增加活性氧的产生，而高度氧化/交联的多肽可能会抵抗蛋白水解，抑制蛋白酶体功能并诱导永久性应激反应。还讨论了防御系统（酶促和非酶促）中与年龄相关的变化的其他可能的解释，这些变化通常与改变的蛋白质的产生相反。 (c) 2006 Elsevier Inc. 保留所有权利。
Accumulation of altered proteins is the most common molecular symptom of ageing. Altered proteins are also associated with many age-related pathologies. Altered proteins are continuously produced but are normally selectively degraded by cellular proteases; their accumulation during ageing may be explained by either or both increased production or decreased elimination. Sources of altered proteins include erroneous synthesis by cytoplasmic and mitochondrial ribosomes, spontaneous deamidation, isomerization and racemization of unstable amino acids residues, damage inflicted by reactive oxygen and nitrogen species, and glycation and cross-linking by glucose and more reactive metabolites. Glycated proteins may damage mitochondria to increase production of reactive oxygen species, while highly oxidised/cross-linked polypeptides may resist proteolysis, inhibit proteasome function and induce a permanent stress response. Other possible explanations for the age-related changes in the defence systems, enzymatic and non-enzymatic, which normally counter generation of altered proteins are also discussed. (c) 2006 Elsevier Inc. All rights reserved.