Are ancient proteins responsible for the age-related decline in health and fitness?
Are ancient proteins responsible for the age-related decline in health and fitness?
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DOI：
10.1089/rej.2009.0938
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发表时间：
2010-03
影响因子：
2.6
通讯作者：
R. Truscott
中科院分区：
文献类型：
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作者：
R. Truscott
身体中有许多蛋白质存在几十年的地方，有时甚至是我们一生的地方。在许多年的时间里，这些蛋白质经历了两种类型的修饰。第一种是由某些氨基酸残基的内在不稳定性引起的，并导致脱酰胺、外消旋和截短。第二种类型可以追溯到细胞代谢过程中产生的反应性生物化学物质对这些古老蛋白质的无情共价修饰，这两种类型的翻译后修饰随着时间的推移而积累，可能对含有这些蛋白质的组织的性质产生重要影响。有人提出，与年龄相关的器官功能下降，如眼睛，心脏，大脑和肺，以及骨骼成分，部分来自这些长寿蛋白质的翻译后修饰。提供的例子中，这可能是一个重要的因素，年龄相关的疾病的病因。由于这些蛋白质的性质随着时间的推移而无情地改变，分子变化导致单个器官和组织（如关节）的功能逐渐下降。身体多个部位的旧蛋白质的这种累积退化也可能限制个体的最终寿命。人类的透镜可能是特别有用的发现，在体内的反应代谢物是最重要的翻译后修饰的长寿蛋白质。
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.