RRC ID 32528
著者 Stenesen D, Suh JM, Seo J, Yu K, Lee KS, Kim JS, Min KJ, Graff JM.
タイトル Adenosine nucleotide biosynthesis and AMPK regulate adult life span and mediate the longevity benefit of caloric restriction in flies.
ジャーナル Cell Metab
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.
巻・号 17(1)
ページ 101-12
公開日 2013-1-8
DOI 10.1016/j.cmet.2012.12.006
PII S1550-4131(12)00497-4
PMID 23312286
PMC PMC3614013
MeSH AMP-Activated Protein Kinases / antagonists & inhibitors AMP-Activated Protein Kinases / genetics AMP-Activated Protein Kinases / metabolism* Adenosine Monophosphate / biosynthesis* Adenosine Triphosphate / metabolism Adenylosuccinate Synthase / genetics Adenylosuccinate Synthase / metabolism Animals Animals, Genetically Modified / metabolism Caloric Restriction Drosophila / enzymology Drosophila / metabolism Fat Body / metabolism Heterozygote Longevity* Mutation RNA Interference
IF 21.567
引用数 95
WOS 分野 ENDOCRINOLOGY & METABOLISM CELL BIOLOGY
リソース情報
ショウジョウバエ P{RS5}CG17273[5-HA-2022] (DGRC#125528)