1999
DOI: 10.1101/gad.13.19.2570
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The SIR2/3/4 complex and SIR2 alone promote longevity in Saccharomyces cerevisiae by two different mechanisms

Abstract: The SIR genes are determinants of life span in yeast mother cells. Here we show that life span regulation by the Sir proteins is independent of their role in nonhomologous end joining. The short life span of a sir3 or sir4 mutant is due to the simultaneous expression of a and ␣ mating-type information, which indirectly causes an increase in rDNA recombination and likely increases the production of extrachromosomal rDNA circles. The short life span of a sir2 mutant also reveals a direct failure to repress recom… Show more

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Cited by 2,010 publications
(1,746 citation statements)
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“…Since the discovery and characterization of the first long‐lived mutants in Caenorhabditis elegans and Saccharomyces cerevisiae more than two decades ago (Kaeberlein, McVey & Guarente, 1999; Kenyon, Chang, Gensch, Rudner & Tabtiang, 1993; Morris, Tissenbaum & Ruvkun, 1996; Ogg et al., 1997; Wang et al., 1993), the concept that aging is a malleable biological process has been well embraced (Finch & Ruvkun, 2001; Gems & Partridge, 2013; Kennedy, 2008; Kenyon, 2005, 2010). …”
Section: Research Organisms For Agingmentioning
confidence: 99%
“…Since the discovery and characterization of the first long‐lived mutants in Caenorhabditis elegans and Saccharomyces cerevisiae more than two decades ago (Kaeberlein, McVey & Guarente, 1999; Kenyon, Chang, Gensch, Rudner & Tabtiang, 1993; Morris, Tissenbaum & Ruvkun, 1996; Ogg et al., 1997; Wang et al., 1993), the concept that aging is a malleable biological process has been well embraced (Finch & Ruvkun, 2001; Gems & Partridge, 2013; Kennedy, 2008; Kenyon, 2005, 2010). …”
Section: Research Organisms For Agingmentioning
confidence: 99%
“…HDACs can be divided into several classes based on sequence homology and cofactor dependency: class I, II and IV HDACs are classical HDACs requiring Zn 2 þ as a cofactor, whereas class III HDACs, also known as Sirtuins, require NAD þ as a cofactor (Imai et al, 2000;Haigis and Guarente, 2006;Yang and Seto, 2007). Control of histone acetylation is associated with longevity regulation in lower organisms (Kaeberlein et al, 1999;Tissenbaum and Guarente, 2001;Rogina and Helfand, 2004;Wood et al, 2004;Dang et al, 2009), and changes in histone acetylation in tissues, such as the brain and liver, correlate with age-dependent declines in tissue function (Oh and Conard, 1972;Shen et al, 2008;Kawakami et al, 2009;Peleg et al, 2010). However, the importance of histone acetylation in aging stem cells is less well studied.…”
Section: Histone Acetylation In Aging Stem Cellsmentioning
confidence: 99%
“…For example, pioneering studies in budding yeast have shown that replicative aging is correlated with heterochromatin loss in telomeric regions, mating type loci, and rDNA repeats (Kim et al ., 1996; Smeal et al ., 1996; Kennedy et al ., 1997). Importantly, overexpression of Sir2, a histone deacetylase required for heterochromatin formation and gene silencing, induces an increased lifespan in yeast (Kaeberlein et al ., 1999). The connection between heterochromatin maintenance and lifespan extension is further strengthened by studies in Caenorhabditis elegans and Drosophila (Rogina & Helfand, 2004; Hashimoto et al ., 2010; Jiang et al ., 2013; Whitaker et al ., 2013).…”
Section: Introductionmentioning
confidence: 99%