2004
DOI: 10.1126/science.1099196
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Abstract: A major cause of aging is thought to result from the cumulative effects of cell loss over time. In yeast, caloric restriction (CR) delays aging by activating the Sir2 deacetylase. Here we show that expression of mammalian Sir2 (SIRT1) is induced in CR rats as well as in human cells that are treated with serum from these animals. Insulin and insulin-like growth factor 1 (IGF-1) attenuated this response. SIRT1 deacetylates the DNA repair factor Ku70, causing it to sequester the proapoptotic factor Bax away from … Show more

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Cited by 1,738 publications
(1,392 citation statements)
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References 22 publications
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“…Therefore, in apparent contrast to other pro-survival and growth promoting signaling mechanisms (e.g., IGF-1 and mTOR), SIRT1 hyperactivity appears to delay ageing, partly through suppression of IGF-1 and mTOR signaling. Consistent with this, SIRT1 expression is induced rather than suppressed by caloric restriction (Cohen et al, 2004) and SIRT1 orthologs are required for lifespan extension via caloric restriction in yeast, worms and flies (Haigis and Guarente, 2006).…”
Section: Sirtuinmentioning
confidence: 55%
“…Therefore, in apparent contrast to other pro-survival and growth promoting signaling mechanisms (e.g., IGF-1 and mTOR), SIRT1 hyperactivity appears to delay ageing, partly through suppression of IGF-1 and mTOR signaling. Consistent with this, SIRT1 expression is induced rather than suppressed by caloric restriction (Cohen et al, 2004) and SIRT1 orthologs are required for lifespan extension via caloric restriction in yeast, worms and flies (Haigis and Guarente, 2006).…”
Section: Sirtuinmentioning
confidence: 55%
“…The mammalian orthologs of Sir2 and Hst2 are SIRT1 and SIRT2, respectively, whereas the FOXO (Forkhead box, class O) subfamily transcription factors, such as FOXO1, FOXO3, FOXO4 and FOXO6, are the mammalian homologs of DAF-16. Caloric restriction stimulates the expression of both SIRT1 and SIRT2 (Cohen et al, 2004;Wang et al, 2007). SIRT1 regulates many cellular processes through deacetylation of various substrates (Verdin, 2007), including FOXO1, FOXO3 and FOXO4 (Brunet et al, 2004;Daitoku et al, 2004;Motta et al, 2004;van der Horst et al, 2004;Yang et al, 2005).…”
Section: Introductionmentioning
confidence: 99%
“…5 Next, Sirt1 expression and activity were studied in rodent tissues during calorie restriction, and it was shown that calorie restriction induced Sirt1 in most tissues, including adipose tissue. 6 Finally, the effects of resveratrol were studied both in vitro and in vivo, demonstrating that the activation of Sirt1 influenced adipose tissue metabolism in rodents. 4 Differentiation of 3T3-L1 cells overexpressing Sirt1 resulted in cells with significantly less lipid accumulation compared to control cells.…”
Section: Introductionmentioning
confidence: 99%