Centre for Gene Regulation and Expression, School of Life Sciences, University of Dundee, Dundee DD1 5EH, UK; Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA 94158-2517, USA; Calico Life Sciences, 1170 Veterans Boulevard, South San Francisco, CA 94080, USA.
Centre for Gene Regulation and Expression, School of Life Sciences, University of Dundee, Dundee DD1 5EH, UK.
Cell Syst. 2016 Aug;3(2):144-159. doi: 10.1016/j.cels.2016.06.011. Epub 2016 Jul 21.
Effective network analysis of protein data requires high-quality proteomic datasets. Here, we report a near doubling in coverage of the C. elegans adult proteome, identifying >11,000 proteins in total with ∼9,400 proteins reproducibly detected in three biological replicates. Using quantitative mass spectrometry, we identify proteins whose abundances vary with age, revealing a concerted downregulation of proteins involved in specific metabolic pathways and upregulation of cellular stress responses with advancing age. Among these are ∼30 peroxisomal proteins, including the PRX-5/PEX5 import protein. Functional experiments confirm that protein import into the peroxisome is compromised in vivo in old animals. We also studied the behavior of the set of age-variant proteins in chronologically age-matched, long-lived daf-2 insulin/IGF-1-pathway mutants. Unexpectedly, the levels of many of these age-variant proteins did not scale with extended lifespan. This indicates that, despite their youthful appearance and extended lifespans, not all aspects of aging are reset in these long-lived mutants.
有效进行蛋白质组学数据的网络分析需要高质量的蛋白质组学数据集。在这里，我们报告了秀丽隐杆线虫成年蛋白质组的覆盖范围几乎翻了一番，总共鉴定出超过 11000 种蛋白质，其中约 9400 种蛋白质在三个生物学重复中可重复检测到。我们使用定量质谱法鉴定了蛋白质丰度随年龄变化的蛋白质，揭示了随着年龄的增长，特定代谢途径相关蛋白的协同下调和细胞应激反应的上调。其中包括约 30 种过氧化物酶体蛋白，包括 PRX-5/PEX5 进口蛋白。功能实验证实，在年老动物体内，过氧化物酶体的蛋白质导入功能受损。我们还研究了与chronologically age-matched（同步年龄匹配）、长寿命 daf-2 胰岛素/IGF-1 信号通路突变体中一组随年龄变化的蛋白质的行为。出乎意料的是，这些随年龄变化的蛋白质中的许多蛋白质的水平并没有随延长的寿命而变化。这表明，尽管这些长寿突变体看起来年轻且寿命延长，但它们并没有重置衰老的所有方面。
