Accurate quantification of more than 4000 mouse tissue proteins reveals minimal proteome changes during aging.
Accurate quantification of more than 4000 mouse tissue proteins reveals minimal proteome changes during aging.
复制标题
DOI：
10.1074/mcp.m110.004523
复制
发表时间：
2011-02
期刊：
影响因子：
--
通讯作者：
Mann M
中科院分区：
文献类型：
--
作者：
Walther DM;Mann M
衰老的生物过程被认为是细胞对生物分子损伤累积的结果。尽管有大量研究涉及衰老哺乳动物组织的突变频率、形态或转录变化，但很少有研究测量蛋白质水平的整体变化。在这里，我们使用整只动物（SILAC 小鼠）的稳定同位素标记和高分辨率质谱法，对 5 或 26 个月大的小鼠的三个大脑区域以及心脏和肾脏进行了深入的蛋白质组学分析。在大脑额叶皮层和海马区，超过 4200 种蛋白质在不同年龄组之间进行了定量比较。在年龄组内和年龄组之间可以观察到个体小鼠之间的蛋白质组差异。然而，在不到 1% 的蛋白质中检测到年轻小鼠和老年小鼠之间平均蛋白质丰度变化超过两倍，而且其中很少有统计学显着性。当比较不同年龄组的小脑、心脏和肾脏时，也得到了类似的结果。因此，出乎意料的是，我们的结果表明，在总体水平上对组织蛋白质组组成的衰老相关影响很小，并且蛋白质稳态在相对较高的年龄下仍然保持功能。
The biological process of aging is believed to be the result of an accumulation of cellular damage to biomolecules. Although there are numerous studies addressing mutation frequencies, morphological or transcriptional changes in aging mammalian tissues, few have measured global changes at the protein level. Here, we present an in depth proteomic analysis of three brain regions as well as heart and kidney in mice aged 5 or 26 months, using stable isotope labeling of whole animals (SILAC mouse) and high resolution mass spectrometry. In the frontal cortex and hippocampal regions of the brain, more than 4200 proteins were quantitatively compared between age groups. Proteome differences between individual mice were observable within and between age groups. However, mean protein abundance changes of more than twofold between young and old mice were detected in less than 1% of all proteins and very few of these were statistically significant. Similar outcomes were obtained when comparing cerebellum, heart, and kidney between age groups. Thus, unexpectedly, our results indicate that aging-related effects on the tissue proteome composition at the bulk level are only minor and that protein homeostasis remains functional up to a relatively high age.