Oxaloacetate supplementation increases lifespan in Caenorhabditis elegans through an AMPK/FOXO-dependent pathway.
Reduced dietary intake increases lifespan in a wide variety of organisms. It also retards disease progression. We tested whether dietary supplementation of citric acid cycle metabolites could mimic this lifespan effect. We report that oxaloacetate supplementation increased lifespan in Caenorhabditis elegans. The increase was dependent on the transcription factor, FOXO/DAF-16, and the energy sensor, AMP-activated protein kinase, indicating involvement of a pathway that is also required for lifespan extension through dietary restriction. These results demonstrate that supplementation of the citric acid cycle metabolite, oxaloacetate, influences a longevity pathway, and suggest a tractable means of introducing the health-related benefits of dietary restriction.
Departments of Pharmacology and Neurosciences, UCSD School of Medicine, University of California-San Diego, La Jolla, CA 92130, USA. dswilliams@ucla.edu
David S
DS
Williams
Alan
A
Cash
Lara
L
Hamadani
Tanja
T
Diemer
D055372:AMP-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism*; D008136:Longevity; D010071:Oxaloacetates / Q000378:metabolism*; D015398:Signal Transduction
D029742:Caenorhabditis elegans Proteins; D051858:Forkhead Transcription Factors; D010071:Oxaloacetates; D055372:AMP-Activated Protein Kinases