Sirtuin activators mimic caloric restriction and delay ageing in metazoans

  title={Sirtuin activators mimic caloric restriction and delay ageing in metazoans},
  author={Jason G. Wood and Blanka Rogina and Siva Lavu and Konrad T. Howitz and Stephen L. Helfand and Marc Tatar and David Sinclair},
Caloric restriction extends lifespan in numerous species. In the budding yeast Saccharomyces cerevisiae this effect requires Sir2 (ref. 1), a member of the sirtuin family of NAD+-dependent deacetylases. Sirtuin activating compounds (STACs) can promote the survival of human cells and extend the replicative lifespan of yeast. Here we show that resveratrol and other STACs activate sirtuins from Caenorhabditis elegans and Drosophila melanogaster, and extend the lifespan of these animals without… 
dSir2 and longevity in Drosophila
Sirtuins: The ‘magnificent seven’, function, metabolism and longevity
The current knowledge regarding the role of sirtuins in metabolism, longevity, and the possible therapeutic applications that could result from the understanding of their function in different organs and pathologies are reviewed.
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It now appears that either activation or inhibition of sirtuins may be desirable for ameliorating disease depending on the pathological condition and the target tissue.
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Recent findings that are beginning to clarify the mechanisms by which CR results in longevity and robust health, which might open new avenues of therapy for diseases of ageing are summarized.
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The findings indicate that SIRT1 can influence many of the major diseases of aging, including metabolic diseases like diabetes, neurodegenerative diseases (Alzheimer's and Huntington's), cancer and osteoporosis, and small molecules that alter the activity of Sirt1 (i.e. CR mimetic drugs) offer a new approach to prevent and possibly treat the major Diseases of aging.


Small molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan
The potent activator resveratrol, a polyphenol found in red wine, lowers the Michaelis constant of SIRT1 for both the acetylated substrate and NAD+, and increases cell survival by stimulating Sirt1-dependent deacetylation of p53.
Requirement of NAD and SIR2 for life-span extension by calorie restriction in Saccharomyces cerevisiae.
These findings suggest that the increased longevity induced by calorie restriction requires the activation of Sir2p by NAD, the oxidized form of nicotinamide adenine dinucleotide.
Increased dosage of a sir-2 gene extends lifespan in Caenorhabditis elegans
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
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An alteration in histone deacetylase activity results in down-regulation in the expression of Rpd3 and increasing expression of the Sir2 in mice.
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An intervention resembling caloric restriction prolongs life span and retards aging in yeast
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The SIR2/3/4 complex and SIR2 alone promote longevity in Saccharomyces cerevisiae by two different mechanisms.
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The aging process may be more specific than previously anticipated on evolutionary grounds because the biology of reactive oxygen species in the mitochondria and elsewhere might be the main determinant of life-span in this organism.
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