Browsing by keyword "Sirtuins"

Now showing items 1-4 of 4

    • C. elegans 14-3-3 proteins regulate life span and interact with SIR-2.1 and DAF-16/FOXO
      Wang, Yamei; Oh, Seung Wook; Deplancke, Bart; Luo, Jianyuan; Walhout, Albertha J. M.; Tissenbaum, Heidi A. (2006-07-25)
      14-3-3 proteins are evolutionarily conserved and ubiquitous proteins that function in a wide variety of biological processes. Here we define a new role for C. elegans 14-3-3 proteins in life span regulation. We identify two C. elegans 14-3-3 proteins as interacting proteins of a major life span regulator, the C. elegans SIR2 ortholog, SIR-2.1. Similar to sir-2.1, we find that overexpression of either 14-3-3 protein (PAR-5 or FTT-2) extends life span and that this is dependent on DAF-16, a forkhead transcription factor (FOXO), another important life span regulator in the insulin/IGF-1 signaling pathway. Furthermore, we show that both 14-3-3 proteins are co-expressed with DAF-16 and SIR-2.1 in the tissues critical for life span regulation. Finally, we show that DAF-16/FOXO also physically interacts with the 14-3-3 proteins. These results suggest that C. elegans 14-3-3 proteins can regulate longevity by cooperating with both SIR-2.1 and DAF-16/FOXO.

    • C. elegans sirtuins
      Viswanathan, Mohan; Tissenbaum, Heidi A. (2013-09-10)
      The nematode Caenorhabditis elegans (C. elegans) has four Sir2 paralogs, sir-2.1, sir-2.2, sir-2.3, and sir-2.4. Thus far, most of the research tools to study worm sirtuins have been developed for sir-2.1, due to its homology to yeast SIR2 and human SIRT1. Here, we have compiled a listing of the currently available strains (including both loss-of-function alleles and transgenics), antibodies, and RNAi constructs relevant to studies on all C. elegans sirtuin family members. We also describe the methods used in the analysis of C. elegans sirtuin function, including life span analysis, various stress-resistance assays, and fat content analysis and provide an overview of all phenotypic data relevant to C. elegans sir-2.1.

    • Overlapping and distinct functions for a Caenorhabditis elegans SIR2 and DAF-16/FOXO
      Wang, Yamei; Tissenbaum, Heidi A. (2006-01-11)
      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.

    • Worming pathways to and from DAF-16/FOXO
      Mukhopadhyay, Arnab; Oh, Seung Wook; Tissenbaum, Heidi A. (2006-07-15)
      In Caenorhabditis elegans, the insulin/IGF-1 signaling pathway controls many biological processes such as life span, fat storage, dauer diapause, reproduction and stress response . This pathway is comprised of many genes including the insulin/IGF-1 receptor (DAF-2) that signals through a conserved PI 3-kinase/AKT pathway and ultimately down-regulates DAF-16, a forkhead transcription factor (FOXO). DAF-16 also receives input from several other pathways that regulate life span such as the germline and the JNK pathway [Hsin, H., Kenyon, C., 1999. Signals from the reproductive system regulate the lifespan of C. elegans. Nature 399, 362-366; Oh, S.W., Mukhopadhyay, A., Svrzikapa, N., Jiang, F., Davis, R.J., Tissenbaum, H.A., 2005. JNK regulates lifespan in Caenorhabditis elegans by modulating nuclear translocation of forkhead transcription factor/DAF-16. Proc. Natl. Acad. Sci. USA 102, 4494-4499]. Therefore, DAF-16 integrates signals from multiple pathways and regulates its downstream target genes to control diverse processes. Here, we discuss the signals to and from DAF-16, with a focus on life span regulation.