Document Detail

Overlapping and distinct functions for a Caenorhabditis elegans SIR2 and DAF-16/FOXO.
MedLine Citation:
PMID:  16280150     Owner:  NLM     Status:  MEDLINE    
The conserved SIR2 protein regulates life span in both yeast and worms: in both organisms overexpression of SIR2 can extend life span and in Caenorhabditis elegans this life span extension is dependent on the forkhead transcription factor, DAF-16. Here, we have done extensive genetic analysis with sir-2.1(ok434), a null mutant of C. elegans sir-2.1, the closest homolog to yeast Sir2p and human SIRT1 to further elucidate its function in life span regulation. sir-2.1(ok434) mutants show a slight decrease in life span as well as sensitivity to various stresses. Our genetic analysis suggests that sir-2.1 is required for life span extension by caloric restriction, independent of the insulin/IGF-1 signaling pathway. Importantly, analysis with unc-13 mutants indicates that sir-2.1 and daf-16 have overlapping and distinct roles in life span regulation. Our expression analysis shows that sir-2.1 has overlapping and distinct expression pattern compared with daf-16, consistent with the results from our genetic data. Our data defines a central role for C. elegans SIR2 in regulation of life span by caloric restriction and demonstrates that sir-2.1 and daf-16 have both overlapping and distinct functions in regulation of C. elegans life span.
Yamei Wang; Heidi A Tissenbaum
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2005-11-08
Journal Detail:
Title:  Mechanisms of ageing and development     Volume:  127     ISSN:  0047-6374     ISO Abbreviation:  Mech. Ageing Dev.     Publication Date:  2006 Jan 
Date Detail:
Created Date:  2005-12-05     Completed Date:  2006-04-25     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0347227     Medline TA:  Mech Ageing Dev     Country:  Ireland    
Other Details:
Languages:  eng     Pagination:  48-56     Citation Subset:  IM    
Program in Gene Function and Expression, Program in Molecular Medicine, Aaron Lazare Research Building, University of Massachusetts Medical School, 364 Plantation Street, Worcester, MA 01605, USA.
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MeSH Terms
Aging / physiology
Caenorhabditis elegans / genetics,  metabolism*
Caenorhabditis elegans Proteins / genetics,  metabolism*
Gene Expression Regulation
Mutation / genetics
Sirtuins / genetics,  metabolism*
Time Factors
Transcription Factors / genetics,  metabolism*
Reg. No./Substance:
0/Caenorhabditis elegans Proteins; 0/Transcription Factors; 0/daf-16 protein, C elegans; EC 3.5.1.-/SIR-2.1 protein, C elegans; EC 3.5.1.-/Sirtuins

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