Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 101, Issue 45, Pages 15998-16003Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0404184101
Keywords
aging; life span; Rpd3; histone deacetylase; Drosophila melanogaster
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Funding
- NIA NIH HHS [AG 16667, R01 AG016667, AG 23088, AG 20816, R03 AG020816, RF1 AG024353, R37 AG016667, R01 AG023088] Funding Source: Medline
- NIEHS NIH HHS [ES 11463] Funding Source: Medline
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Calorie restriction can extend life span in a variety of species including mammals, flies, nematodes, and yeast. Despite the importance of this nearly universal effect, little is understood about the molecular mechanisms that mediate the life-span-extending effect of calorie restriction in metazoans. Sir2 is known to be involved in life span determination and calorie restriction in yeast mother cells. In nematodes increased Sir2 can extend life span, but a direct link to calorie restriction has not been demonstrated. We now report that Sir2 is directly involved in the calorie-restriction life-span-extending pathway in Drosophila. We demonstrate that an increase in Drosophila Sir2 (dSir2) extends life span, whereas a decrease in dSir2 blocks the life-span-extending effect of calorie reduction or rpd3 mutations. These data lead us to propose a genetic pathway by which calorie restriction extends life span and provides a framework for genetic and pharmacological studies of life span extension in metazoans.
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