A role for SIR-2.1 regulation of ER stress response genes in determining C. elegans life span.

Authors: Viswanathan M; Kim SK; Berdichevsky A; Guarente L

Abstract: C. elegans SIR-2.1, a member of the Sir-2 family of NAD(+)-dependent protein deacetylases, has been shown to regulate nematode aging via the insulin/IGF pathway transcription factor daf-16. Treatment of C. elegans with the small molecule resveratrol, however, extends life span in a manner fully dependent upon sir-2.1, but independent of daf-16. Microarray analysis of worms treated with resveratrol demonstrates the transcriptional induction of a family of genes encoding prion-like glutamine/asparagine-rich proteins involved in endoplasmic reticulum (ER) stress response to unfolded proteins. RNA interference of abu-11, a member of this ER stress gene family, abolishes resveratrol-mediated life span extension, and overexpression of abu-11 extends the life span of transgenic animals. Furthermore, SIR-2.1 normally represses transcription of abu-11 and other ER stress gene family members, indicating that resveratrol extends life span by inhibiting sir-2.1-mediated repression of ER stress genes. Our findings demonstrate that abu-11 and other members of its ER stress gene family are positive determinants of C. elegans life span.

Keywords: Animals; Asparagine/chemistry; Caenorhabditis elegans/drug effects/genetics/*physiology; Caenorhabditis elegans Proteins/genetics/*metabolism; Endoplasmic Reticulum/drug effects/*genetics/*metabolism; Fungal Proteins/*metabolism; Gene Expression Profiling; Glutamine/chemistry; Heat-Shock Proteins/genetics/*metabolism; Longevity/drug effects/genetics; RNA Interference/drug effects/physiology; Sirtuins/*metabolism; Stilbenes/pharmacology; Transcription, Genetic/drug effects/genetics
Journal: Developmental cell
Volume: 9
Issue: 5
Pages: 605-15
Date: Nov. 1, 2005
PMID: 16256736
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Citation:

Viswanathan M, Kim SK, Berdichevsky A, Guarente L (2005) A role for SIR-2.1 regulation of ER stress response genes in determining C. elegans life span. Developmental cell 9: 605-15.


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