Proteomic analysis of age‐dependent changes in protein solubility identifies genes that modulate lifespan

Aging Cell

Reis‐Rodrigues, Pedro²  Czerwieniec, Gregg²  Peters, Theodore W.²  Evani, Uday S.²  Alavez, Silvestre²  Gaman, Emily A.²  Vantipalli, Maithili²  Mooney, Sean D.²  Gibson, Bradford W.¹  Lithgow, Gordon J.¹  Hughes, Robert E.¹ 

[1] The Interdisciplinary Research Consortium on Geroscience, The Buck Institute for Research on Aging, 8001 Redwood Blvd., Novato, CA 94949, USA

关键词: C. elegans;    lifespan;    aging;    protein solubility;    protein aggregation;   

DOI  :  10.1111/j.1474-9726.2011.00765.x

来源: Wiley

【 摘 要 】

Summary

While it is generally recognized that misfolding of specific proteins can cause late-onset disease, the contribution of protein aggregation to the normal aging process is less well understood. To address this issue, a mass spectrometry-based proteomic analysis was performed to identify proteins that adopt sodium dodecyl sulfate (SDS)-insoluble conformations during aging in Caenorhabditis elegans. SDS-insoluble proteins extracted from young and aged C. elegans were chemically labeled by isobaric tagging for relative and absolute quantification (iTRAQ) and identified by liquid chromatography and mass spectrometry. Two hundred and three proteins were identified as being significantly enriched in an SDS-insoluble fraction in aged nematodes and were largely absent from a similar protein fraction in young nematodes. The SDS-insoluble fraction in aged animals contains a diverse range of proteins including a large number of ribosomal proteins. Gene ontology analysis revealed highly significant enrichments for energy production and translation functions. Expression of genes encoding insoluble proteins observed in aged nematodes was knocked down using RNAi, and effects on lifespan were measured. 41% of genes tested were shown to extend lifespan after RNAi treatment, compared with 18% in a control group of genes. These data indicate that genes encoding proteins that become insoluble with age are enriched for modifiers of lifespan. This demonstrates that proteomic approaches can be used to identify genes that modify lifespan. Finally, these observations indicate that the accumulation of insoluble proteins with diverse functions may be a general feature of aging.

【 授权许可】

Unknown   
Published 2011. This article is a U.S. Government work and is in the public domain in the USA. Aging Cell © 2011 Blackwell Publishing Ltd/Anatomical Society of Great Britain and Ireland