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) |