Adenosine nucleotide biosynthesis and AMPK regulate adult life span and mediate the longevity benefit of caloric restriction in flies

Drew Stenesen, Jae Myoung Suh, Jin Seo, Kweon Yu, Kyu Sun Lee, Jong Seok Kim, Kyung Jin Min, Jonathan M. Graff

Research output: Contribution to journalArticle

97 Scopus citations

Abstract

A common thread among conserved life span regulators lies within intertwined roles in metabolism and energy homeostasis. We show that heterozygous mutations of AMP biosynthetic enzymes extend Drosophila life span. The life span benefit of these mutations depends upon increased AMP:ATP and ADP:ATP ratios and adenosine monophosphate-activated protein kinase (AMPK). Transgenic expression of AMPK in adult fat body or adult muscle, key metabolic tissues, extended life span, while AMPK RNAi reduced life span. Supplementing adenine, a substrate for AMP biosynthesis, to the diet of long-lived AMP biosynthesis mutants reversed life span extension. Remarkably, this simple change in diet also blocked the prolongevity effects of dietary restriction. These data establish AMP biosynthesis, adenosine nucleotide ratios, and AMPK as determinants of adult life span; provide a mechanistic link between cellular anabolism and energy sensing pathways; and indicate that dietary adenine manipulations might alter metabolism to influence animal life span.

Original languageEnglish (US)
Pages (from-to)101-112
Number of pages12
JournalCell Metabolism
Volume17
Issue number1
DOIs
StatePublished - Jan 8 2013

ASJC Scopus subject areas

  • Physiology
  • Molecular Biology
  • Cell Biology

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