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Sir2 mediates longevity in the fly through a pathway related to calorie restriction

2004· article· en· 1,353 citations· W1997145913 on OpenAlex· 10.1073/pnas.0404184101

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Abstract

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.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

The record

Venue
Proceedings of the National Academy of Sciences
Topic
Genetics, Aging, and Longevity in Model Organisms
Field
Biochemistry, Genetics and Molecular Biology
Canadian institutions
Funders
National Institute of Environmental Health SciencesNational Institute on AgingEllison Medical FoundationPatrick and Catherine Weldon Donaghue Medical Research FoundationStockholms UniversitetHospital for Sick ChildrenNational Institutes of HealthYale University
Keywords
Calorie restrictionLongevityBiologyLife spanDrosophila (subgenus)GeneticsDrosophila melanogasterGeneEvolutionary biologyEndocrinology
Has abstract in OpenAlex
yes