Department of Biochemical Sciences, Sapienza University of Rome, 00185 Rome, Italy.
Department of Chemistry, Center of Membrane Sciences, and Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY 40506, United States.
Ageing Res Rev. 2014 Jan;13:75-89. doi: 10.1016/j.arr.2013.12.005. Epub 2013 Dec 25.
It is well established that the risk to develop neurodegenerative disorders increases with chronological aging. Accumulating studies contributed to characterize the age-dependent changes either at gene and protein expression level which, taken together, show that aging of the human brain results from the combination of the normal decline of multiple biological functions with environmental factors that contribute to defining disease risk of late-life brain disorders. Finding the "way out" of the labyrinth of such complex molecular interactions may help to fill the gap between "normal" brain aging and development of age-dependent diseases. To this purpose, proteomics studies are a powerful tool to better understand where to set the boundary line of healthy aging and age-related disease by analyzing the variation of protein expression levels and the major post translational modifications that determine "protein" physio/pathological fate. Increasing attention has been focused on oxidative modifications due to the crucial role of oxidative stress in aging, in addition to the fact that this type of modification is irreversible and may alter protein function. Redox proteomics studies contributed to decipher the complexity of brain aging by identifying the proteins that were increasingly oxidized and eventually dysfunctional as a function of age. The purpose of this review is to summarize the most important findings obtained by applying proteomics approaches to murine models of aging with also a brief overview of some human studies, in particular those related to dementia.
众所周知，神经退行性疾病的发病风险随着年龄的增长而增加。越来越多的研究有助于描述基因和蛋白质表达水平随年龄变化的特征，这些特征表明，人类大脑的衰老源于多种生物功能正常下降与环境因素的共同作用，这些因素导致晚年大脑疾病的发病风险。找到这种复杂分子相互作用的“出路”，可能有助于填补“正常”大脑衰老与年龄相关性疾病之间的空白。为此，蛋白质组学研究是一个强大的工具，可以通过分析蛋白质表达水平的变化和决定“蛋白质”生理/病理命运的主要翻译后修饰，更好地了解健康衰老和与年龄相关的疾病的界限在哪里。由于氧化应激在衰老过程中的关键作用，以及这种类型的修饰是不可逆的，可能会改变蛋白质的功能，因此氧化修饰受到了越来越多的关注。氧化还原蛋白质组学研究通过鉴定随着年龄的增长而逐渐氧化并最终功能失调的蛋白质，有助于揭示大脑衰老的复杂性。本文综述的目的是总结通过应用蛋白质组学方法在衰老的小鼠模型中获得的最重要的发现，并简要概述一些人类研究，特别是与痴呆症相关的研究。
