Deep Proteome Analysis Identifies Age-Related Processes in C. elegans.
Deep Proteome Analysis Identifies Age-Related Processes in C. elegans.
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DOI：
10.1016/j.cels.2016.06.011
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发表时间：
2016-08
期刊：
影响因子：
9.3
通讯作者：
Kenyon C
中科院分区：
文献类型：
--
作者：
Narayan V;Ly T;Pourkarimi E;Murillo AB;Gartner A;Lamond AI;Kenyon C
有效的蛋白质数据网络分析需要高质量的蛋白质组学数据集。在这里，我们报告了线虫成体蛋白质组的覆盖率几乎翻了一番，共鉴定了bb1011000个蛋白质，在三个生物重复中可重复检测到约9400个蛋白质。使用定量质谱法，我们鉴定了丰度随年龄变化的蛋白质，揭示了参与特定代谢途径的蛋白质的协同下调和随着年龄增长的细胞应激反应的上调。其中约有30种过氧化物酶体蛋白，包括PRX-5/PEX5输入蛋白。功能实验证实，老年动物体内蛋白质输入过氧化物酶体受到损害。我们还研究了年龄匹配、长寿的daf-2胰岛素/ igf -1途径突变体中一组年龄变异蛋白的行为。出乎意料的是，许多这些年龄变异蛋白的水平并没有随着寿命的延长而增加。这表明，尽管他们的外表年轻，寿命延长，但并不是衰老的所有方面都在这些长寿的突变体中被重置。在胰岛素/IGF-1突变体中，大多数年龄变异蛋白不随生物年龄变化而变化，对成年秀丽隐杆线虫的深度蛋白质组学分析提供了宝贵的资源，揭示了衰老过程中过氧化物酶体蛋白输入的失败，令人惊讶的是，在长寿的胰岛素/IGF-1突变体中，大多数年龄变异蛋白水平的变化率与生物衰老的降低率不成比例。
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. Near doubling in C. elegans proteome coverage with age-dependent protein measurements Putative sub-cellular localization assignments for >6,000 nematode proteins Peroxisome protein import impaired during aging Most age-variant proteins do not scale with biological age in insulin/IGF-1 mutants Deep proteome analysis of adult C. elegans provides a valuable resource, reveals a failure in peroxisome protein import during aging, and, surprisingly, shows that the rates of change in the levels of the majority of age-variant proteins do not scale with the reduced rate of biological aging in long-lived insulin/IGF-1 mutants.
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影响因子：
9.8
作者：
David DC;Ollikainen N;Trinidad JC;Cary MP;Burlingame AL;Kenyon C
通讯作者：
Kenyon C
影响因子：
64.5
作者：
Budovskaya YV;Wu K;Southworth LK;Jiang M;Tedesco P;Johnson TE;Kim SK
通讯作者：
Kim SK
DOI：
10.1073/pnas.0400848101
发表时间：
2004-05-25
影响因子：
11.1
作者：
Huang, C;Xiong, CJ;Kornfeld, K
通讯作者：
Kornfeld, K
影响因子：
64.8
作者：
Herndon, LA;Schmeissner, PJ;Driscoll, M
通讯作者：
Driscoll, M
影响因子：
8.8
作者：
Gruen, Dominic;Kirchner, Marieluise;Rajewsky, Nikolaus
通讯作者：
Rajewsky, Nikolaus