Deep Proteome Analysis Identifies Age-Related Processes in C. elegans

被引:83
作者
Narayan, Vikram [1 ,2 ,3 ]
Ly, Tony [1 ]
Pourkarimi, Ehsan [1 ,4 ]
Murillo, Alejandro Brenes [1 ]
Gartner, Anton [1 ]
Lamond, Angus I. [1 ]
Kenyon, Cynthia [2 ,3 ]
机构
[1] Univ Dundee, Sch Life Sci, Ctr Gene Regulat & Express, Dundee DD1 5EH, Scotland
[2] Univ Calif San Francisco, Dept Biochem & Biophys, San Francisco, CA 94158 USA
[3] Calico Life Sci, 1170 Vet Blvd, San Francisco, CA 94080 USA
[4] Mem Sloan Kettering Canc Ctr, New York, NY 10065 USA
基金
英国惠康基金;
关键词
LIFE-SPAN REGULATION; HEAT-SHOCK FACTOR; CAENORHABDITIS-ELEGANS; GENES; LONGEVITY; GENETICS; MASS; INTERFERENCE; EXPRESSION; KNOWLEDGE;
D O I
10.1016/j.cels.2016.06.011
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 similar to 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 similar to 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.
引用
收藏
页码:144 / 159
页数:16
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