Rates of behavior and aging specified by mitochondrial function during development.
To explore the role of mitochondrial activity in the aging process, we have lowered the activity of the electron transport chain and adenosine 5'-triphosphate (ATP) synthase with RNA interference (RNAi) in Caenorhabditis elegans. These perturbations reduced body size and behavioral rates and extended adult life-span. Restoring messenger RNA to near-normal levels during adulthood did not elevate ATP levels and did not correct any of these phenotypes. Conversely, inhibiting respiratory-chain components during adulthood only did not reset behavioral rates and did not affect life-span. Thus, the developing animal appears to contain a regulatory system that monitors mitochondrial activity early in life and, in response, establishes rates of respiration, behavior, and aging that persist during adulthood.
Dillin
Andrew
A
Department of Biochemistry and Biophysics, University of California, San Francisco, CA 94143-0448, USA.
Hsu
Ao-Lin
AL
Arantes-Oliveira
Nuno
N
Lehrer-Graiwer
Joshua
J
Hsin
Honor
H
Fraser
Andrew G
AG
Kamath
Ravi S
RS
Ahringer
Julie
J
Kenyon
Cynthia
C
D000375:Aging; D000818:Animals; D001522:Behavior, Animal; D017173:Caenorhabditis elegans / Q000166:cytology / Q000254:growth & development / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism; D048429:Cell Size; D004579:Electron Transport; D042967:Electron Transport Complex I; D014450:Electron Transport Complex III / Q000235:genetics / Q000378:metabolism; D003576:Electron Transport Complex IV / Q000235:genetics / Q000378:metabolism; D004722:Endoribonucleases / Q000235:genetics / Q000378:metabolism; D005247:Feeding Behavior; D051858:Forkhead Transcription Factors; D007506:Iron-Sulfur Proteins / Q000235:genetics / Q000378:metabolism; D008136:Longevity; D008928:Mitochondria / Q000378:metabolism*; D025261:Mitochondrial Proton-Translocating ATPases / Q000235:genetics / Q000378:metabolism; D009068:Movement; D009245:NADH Dehydrogenase / Q000235:genetics / Q000378:metabolism; D009247:NADH, NADPH Oxidoreductases / Q000235:genetics / Q000378:metabolism; D010101:Oxygen Consumption; D010641:Phenotype; D034622:RNA Interference; D012330:RNA, Double-Stranded / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011972:Receptor, Insulin / Q000235:genetics / Q000378:metabolism; D043244:Ribonuclease III; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
D029742:Caenorhabditis elegans Proteins; D051858:Forkhead Transcription Factors; D007506:Iron-Sulfur Proteins; D012330:RNA, Double-Stranded; D012333:RNA, Messenger; D014157:Transcription Factors; C108831:daf-16 protein, C elegans; C443102:Isp-1 protein, Caenorhabditis elegans; D009247:NADH, NADPH Oxidoreductases; D009245:NADH Dehydrogenase; D003576:Electron Transport Complex IV; C107483:DAF-2 protein, C elegans; D011972:Receptor, Insulin; D004722:Endoribonucleases; D043244:Ribonuclease III; D025261:Mitochondrial Proton-Translocating ATPases; D042967:Electron Transport Complex I; D014450:Electron Transport Complex III