Save Sight Institute, University of Sydney, Sydney, NSW, Australia.
Rejuvenation Res. 2010 Feb;13(1):83-9. doi: 10.1089/rej.2009.0938.
There are a number of sites in the body where proteins are present for decades and sometimes for all of our lives. Over a period of many years, such proteins are subject to two types of modifications. The first results from the intrinsic instability of certain amino acid residues and leads to deamidation, racemization, and truncation. The second type can be traced to relentless covalent modification of such ancient proteins by reactive biochemicals produced during cellular metabolism.The accumulation of both types of posttranslational modifications over time may have important consequences for the properties of tissues that contain such proteins. It is proposed that the age-related decline in function of organs such as the eye, heart, brain, and lung, as well as skeletal components, comes about, in part, from the posttranslational modification of these long-lived proteins. Examples are provided in which this may be an important factor in the etiology of age-related conditions. As the properties of these proteins alter inexorably over time, the molecular changes contribute to a gradual decline in the function of individual organs and also tissues such as joints. This cumulative degeneration of old proteins at multiple sites in the body may also constrain the ultimate life span of the individual. The human lens may be particularly useful for discovering which reactive metabolites in the body are of most importance for posttranslational modification of long-lived proteins.
体内有许多蛋白质存在的部位，这些蛋白质可以存在几十年，甚至我们的一生。多年来，这些蛋白质会经历两种类型的修饰。第一种是由于某些氨基酸残基的固有不稳定性而导致的脱酰胺、消旋和截断。第二种可以追溯到细胞代谢过程中产生的反应性生化物质对这些古老蛋白质的无情共价修饰。随着时间的推移，这两种类型的翻译后修饰的积累可能对含有这些蛋白质的组织的特性产生重要影响。有人提出，眼睛、心脏、大脑、肺以及骨骼等器官的功能随着年龄的增长而下降，部分原因是这些长寿命蛋白质的翻译后修饰。提供了一些例子，说明这可能是与年龄相关疾病病因的一个重要因素。随着这些蛋白质的性质随着时间的推移不可避免地发生变化，分子变化导致单个器官以及关节等组织的功能逐渐下降。这种在体内多个部位的旧蛋白质的累积退化也可能限制个体的最终寿命。人眼可能特别有助于发现体内哪些反应性代谢物对长寿命蛋白质的翻译后修饰最重要。
