Gene Symbol: sir-2.1
Description: NAD-dependent protein deacetylase sir-2.1;yeast SIR related
Alias: NAD-dependent protein deacetylase sir-2.1;yeast SIR related
Species: Caenorhabditis elegans
Products:     sir-2.1

Top Publications

  1. Greiss S, Hall J, Ahmed S, Gartner A. C. elegans SIR-2.1 translocation is linked to a proapoptotic pathway parallel to cep-1/p53 during DNA damage-induced apoptosis. Genes Dev. 2008;22:2831-42 pubmed publisher
    ..SIR-2.1 translocation is an early event in germ cell apoptosis and is independent of apoptosis execution and cep-1, raising the possibility that SIR-2.1 translocation is linked to the induction of DNA damage-induced apoptosis. ..
  2. Burnett C, Valentini S, Cabreiro F, Goss M, Somogyvári M, Piper M, et al. Absence of effects of Sir2 overexpression on lifespan in C. elegans and Drosophila. Nature. 2011;477:482-5 pubmed publisher
    ..Our findings do not rule out a role for sirtuins in determination of metazoan lifespan, but they do cast doubt on the robustness of the previously reported effects of sirtuins on lifespan in C. elegans and Drosophila. ..
  3. Wood J, Rogina B, Lavu S, Howitz K, Helfand S, Tatar M, et al. Sirtuin activators mimic caloric restriction and delay ageing in metazoans. Nature. 2004;430:686-9 pubmed
    ..Lifespan extension is dependent on functional Sir2, and is not observed when nutrients are restricted. Together these data indicate that STACs slow metazoan ageing by mechanisms that may be related to caloric restriction. ..
  4. Wang Y, Tissenbaum H. Overlapping and distinct functions for a Caenorhabditis elegans SIR2 and DAF-16/FOXO. Mech Ageing Dev. 2006;127:48-56 pubmed
    ..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. ..
  5. Berdichevsky A, Viswanathan M, Horvitz H, Guarente L. C. elegans SIR-2.1 interacts with 14-3-3 proteins to activate DAF-16 and extend life span. Cell. 2006;125:1165-77 pubmed
    ..We propose the existence of a stress-dependent pathway in which SIR-2.1 and 14-3-3 act in parallel to the insulin-like pathway to activate DAF-16 and extend life span. ..
  6. Rizki G, Iwata T, Li J, Riedel C, Picard C, Jan M, et al. The evolutionarily conserved longevity determinants HCF-1 and SIR-2.1/SIRT1 collaborate to regulate DAF-16/FOXO. PLoS Genet. 2011;7:e1002235 pubmed publisher
    ..Our findings uncover a conserved interaction between the key longevity determinants SIR-2.1/SIRT1 and HCF-1, and they provide new insights into the complex regulation of FOXO proteins. ..
  7. Tissenbaum H, Guarente L. Increased dosage of a sir-2 gene extends lifespan in Caenorhabditis elegans. Nature. 2001;410:227-30 pubmed
    ..1 transgene functions upstream of daf-16 in the insulin-like signalling pathway. Our findings suggest that Sir2 proteins may couple longevity to nutrient availability in many eukaryotic organisms. ..
  8. Bizat N, Peyrin J, Haïk S, Cochois V, Beaudry P, Laplanche J, et al. Neuron dysfunction is induced by prion protein with an insertional mutation via a Fyn kinase and reversed by sirtuin activation in Caenorhabditis elegans. J Neurosci. 2010;30:5394-403 pubmed publisher
    ..Sirtuin activators may thus have therapeutic potential to protect from prion neurotoxicity and its effects on intracellular signaling. ..
  9. Walker A, Yang F, Jiang K, Ji J, Watts J, Purushotham A, et al. Conserved role of SIRT1 orthologs in fasting-dependent inhibition of the lipid/cholesterol regulator SREBP. Genes Dev. 2010;24:1403-17 pubmed publisher
    ..These findings may have important biomedical implications for the treatment of metabolic disorders associated with aberrant lipid/cholesterol homeostasis, including metabolic syndrome and atherosclerosis. ..

More Information


  1. Wang Y, Oh S, Deplancke B, Luo J, Walhout A, Tissenbaum H. C. elegans 14-3-3 proteins regulate life span and interact with SIR-2.1 and DAF-16/FOXO. Mech Ageing Dev. 2006;127:741-7 pubmed
    ..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. ..
  2. Guo X, Garcia L. SIR-2.1 integrates metabolic homeostasis with the reproductive neuromuscular excitability in early aging male Caenorhabditis elegans. elife. 2014;3:e01730 pubmed publisher
    ..DOI: ..
  3. Kim J, Kang Y, Lee J, Choi D, Cho Y, Shin J, et al. The natural phytochemical dehydroabietic acid is an anti-aging reagent that mediates the direct activation of SIRT1. Mol Cell Endocrinol. 2015;412:216-25 pubmed publisher
  4. Kashyap S, Johnson J, McCue H, Chen X, Edmonds M, Ayala M, et al. Caenorhabditis elegans dnj-14, the orthologue of the DNAJC5 gene mutated in adult onset neuronal ceroid lipofuscinosis, provides a new platform for neuroprotective drug screening and identifies a SIR-2.1-independent action of resveratrol. Hum Mol Genet. 2014;23:5916-27 pubmed publisher
    ..The Sirtuin-independent neuroprotective action of resveratrol revealed here suggests potential therapeutic applications for ANCL and possibly other human neurodegenerative diseases. ..
  5. Mouchiroud L, Houtkooper R, Moullan N, Katsyuba E, Ryu D, Canto C, et al. The NAD(+)/Sirtuin Pathway Modulates Longevity through Activation of Mitochondrial UPR and FOXO Signaling. Cell. 2013;154:430-41 pubmed publisher
    ..Our data suggest that augmenting mitochondrial stress signaling through the modulation of NAD(+) levels may be a target to improve mitochondrial function and prevent or treat age-associated decline. ..
  6. Wang X, Wang X, Li L, Wang D. Lifespan extension in Caenorhabditis elegans by DMSO is dependent on sir-2.1 and daf-16. Biochem Biophys Res Commun. 2010;400:613-8 pubmed publisher
    ..1 and daf-16 but not eat-2 or hsf-1. In summary, we report the function and the putative mechanism of DMSO in lifespan extension of C. elegans. This study draws attention to using DMSO as a solvent when conducting aging studies. ..
  7. Jadiya P, Chatterjee M, Sammi S, Kaur S, Palit G, Nazir A. Sir-2.1 modulates 'calorie-restriction-mediated' prevention of neurodegeneration in Caenorhabditis elegans: implications for Parkinson's disease. Biochem Biophys Res Commun. 2011;413:306-10 pubmed publisher
    ..Our studies provide evidence that calorie restriction affords, an sir-2.1 mediated, protection against the dopaminergic neurodegeneration, that might have implications for neurodegenerative Parkinson's disease. ..
  8. Raynes R, Leckey B, Nguyen K, Westerheide S. Heat shock and caloric restriction have a synergistic effect on the heat shock response in a sir2.1-dependent manner in Caenorhabditis elegans. J Biol Chem. 2012;287:29045-53 pubmed publisher
    ..1-dependent manner. Finally, we show that caloric restriction increases the ability of heat shock to preserve movement in a polyglutamine toxicity neurodegenerative disease model and that this effect is dependent on sir2.1. ..
  9. Ludewig A, Izrayelit Y, Park D, Malik R, Zimmermann A, Mahanti P, et al. Pheromone sensing regulates Caenorhabditis elegans lifespan and stress resistance via the deacetylase SIR-2.1. Proc Natl Acad Sci U S A. 2013;110:5522-7 pubmed publisher
    ..These findings strengthen the link between chemosensory inputs and conserved mechanisms of lifespan regulation in metazoans and suggest a model for communal lifespan regulation in C. elegans...
  10. Heidler T, Hartwig K, Daniel H, Wenzel U. Caenorhabditis elegans lifespan extension caused by treatment with an orally active ROS-generator is dependent on DAF-16 and SIR-2.1. Biogerontology. 2010;11:183-95 pubmed publisher
    ..1-dependent alterations in gene expression after a ROS challenge lead to a lifespan extension in C. elegans as long as the stressor concentration does not exceed the saturable protective capacity. ..
  11. Pan K, Palter J, Rogers A, Olsen A, Chen D, Lithgow G, et al. Inhibition of mRNA translation extends lifespan in Caenorhabditis elegans. Aging Cell. 2007;6:111-9 pubmed
    ..Thus, mRNA translation exerts pleiotropic effects on growth, reproduction, stress resistance and lifespan in C. elegans. ..
  12. Mair W, Panowski S, Shaw R, Dillin A. Optimizing dietary restriction for genetic epistasis analysis and gene discovery in C. elegans. PLoS ONE. 2009;4:e4535 pubmed publisher
    ..1, highlighting the importance of first optimizing DR to identify universal regulators of DR mediated longevity. ..
  13. Parker J, Vázquez Manrique R, Tourette C, Farina F, Offner N, Mukhopadhyay A, et al. Integration of ?-catenin, sirtuin, and FOXO signaling protects from mutant huntingtin toxicity. J Neurosci. 2012;32:12630-40 pubmed publisher
    ..Taken together, these results suggest that integration of ?-catenin, sirtuin and FOXO signaling protects from the early phases of mutant huntingtin toxicity. ..
  14. Fitzenberger E, Deusing D, Marx C, Boll M, Lüersen K, Wenzel U. The polyphenol quercetin protects the mev-1 mutant of Caenorhabditis elegans from glucose-induced reduction of survival under heat-stress depending on SIR-2.1, DAF-12, and proteasomal activity. Mol Nutr Food Res. 2014;58:984-94 pubmed publisher
    ..SIR-2.1, DAF-12, and MDT-15 were identified as targets that activate unfolded protein response and proteasomal degradation to limit the accumulation of functionally restricted proteins. ..
  15. Morselli E, Maiuri M, Markaki M, Megalou E, Pasparaki A, Palikaras K, et al. The life span-prolonging effect of sirtuin-1 is mediated by autophagy. Autophagy. 2010;6:186-8 pubmed
    ..elegans, our results suggest that caloric restriction and resveratrol extend longevity, at least in experimental settings, by activating autophagy. ..
  16. Berdichevsky A, Nedelcu S, Boulias K, Bishop N, Guarente L, Horvitz H. 3-Ketoacyl thiolase delays aging of Caenorhabditis elegans and is required for lifespan extension mediated by sir-2.1. Proc Natl Acad Sci U S A. 2010;107:18927-32 pubmed publisher
    ..Our findings suggest that defects in fatty acid oxidation can limit lifespan and accelerate aging in C. elegans and that kat-1-mediated fatty acid oxidation is crucial for overexpressed sir-2.1 to delay aging. ..
  17. Hashimoto T, Horikawa M, Nomura T, Sakamoto K. Nicotinamide adenine dinucleotide extends the lifespan of Caenorhabditis elegans mediated by sir-2.1 and daf-16. Biogerontology. 2010;11:31-43 pubmed publisher
    ..1 and DAF-16 along a signaling pathway, namely insulin-like signalling pathway (at least parts of it), different from that associated with caloric restriction. ..
  18. Wirth M, Paap F, Fischle W, Wenzel D, Agafonov D, Samatov T, et al. HIS-24 linker histone and SIR-2.1 deacetylase induce H3K27me3 in the Caenorhabditis elegans germ line. Mol Cell Biol. 2009;29:3700-9 pubmed publisher
    ..Overall, our data indicate that SIR-2.1 and HIS-24 contribute to the propagation of a specialized chromatin state at the subtelomeric regions and elsewhere in the genome. ..