Overlapping and distinct functions for a Caenorhabditis elegans SIR2 and DAF-16/FOXO.
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.
Wang
Yamei
Y
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.
Tissenbaum
Heidi A
HA
D000375:Aging / Q000502:physiology; D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D051858:Forkhead Transcription Factors; D005786:Gene Expression Regulation; D009154:Mutation / Q000235:genetics; D037761:Sirtuins / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
D029742:Caenorhabditis elegans Proteins; D051858:Forkhead Transcription Factors; D014157:Transcription Factors; C108831:daf-16 protein, C elegans; C507014:SIR-2.1 protein, C elegans; D037761:Sirtuins