Cited by 1,603

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Increased dosage of a sir-2 gene extends lifespan in Caenorhabditis elegans

Tissenbaum, Heidi A., Guarente, Leonard·2001·Nature

Abstract

In Caenorhabditis elegans, mutations that reduce the activity of an insulin-like receptor (daf-2) or a phosphatidylinositol-3-OH kinase (age-1) favour entry into the dauer state during larval development and extend lifespan in adults. Downregulation of this pathway activates a forkhead transcription factor (daf-16), which may regulate targets that promote dauer formation in larvae and stress resistance and longevity in adults. In yeast, the SIR2 gene determines the lifespan of mother cells, and adding an extra copy of SIR2 extends lifespan. Sir2 mediates chromatin silencing through a histone deacetylase activity that depends on NAD (nicotinamide adenine dinucleotide) as a cofactor. We have surveyed the lifespan of C. elegans strains containing duplications of chromosomal regions. Here we report that a duplication containing sir-2.1-the C. elegans gene most homologous to yeast SIR2-confers a lifespan that is extended by up to 50%. Genetic analysis indicates that the sir-2.1 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.

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Crossref · 10.1038/35065638

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4 of 4 references verified0 citation errors · 0 not checkable

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  • Enhanced expression of the worm sir-2.1 and fly dSir2 orthologs could extend lifespan in both invertebrate model systems.

    “and subsequent reports indicated that enhanced expression of the worm (sir-2.1) and fly (dSir2) orthologs could extend lifespan in both invertebrate model systems (Rogina and Helfand, 2004; Tissenbaum and Guarente, 2001).”

    From The Hallmarks of Aging (2013) · cites this paper as Tissenbaum and Guarente, 2001

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Research works printed but not linked: 23

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Metadata

Authors
Tissenbaum, H. A., & Guarente, L.
Venue
Nature
Published
2001-03
Volume
410
Issue
6825
Pages
227-230
ISSN
  • 0028-0836
  • 1476-4687
Cited by
1,603
References
4
Language
en

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