Authors: Wang Y; Tissenbaum HA
Abstract: 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.
Keywords: Aging/physiology; Animals; Caenorhabditis elegans/genetics/*metabolism; Caenorhabditis elegans Proteins/genetics/*metabolism; Gene Expression Regulation; Mutation/genetics; Sirtuins/genetics/*metabolism; Time Factors; Transcription Factors/genetics/*metabolism|
Journal: Mechanisms of ageing and development Volume: 127 Issue: 1 Pages: 48-56 Date: Nov. 11, 2005 PMID: 16280150 |
Wang Y, Tissenbaum HA (2006) Overlapping and distinct functions for a Caenorhabditis elegans SIR2 and DAF-16/FOXO. Mechanisms of ageing and development 127: 48-56.
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