DAF-2 pathway mutations and food restriction in aging Caenorhabditis elegans differentially affect metabolism.
In Caenorhabditis elegans, metabolism and life expectancy respond to environmental cues of food availability and temperature. Several genes act in a neuroendocrine, DAF-2, insulin/IGF-1 receptor-like pathway in which reduced signaling affects metabolism and increases longevity. Here we describe the effect of reduced DAF-2 signaling on several parameters of metabolism including rates of oxygen consumption and heat output, the calorimetric/respirometric ratio, ATP levels, XTT reduction capacity and accumulation of lipofuscin. We also asked whether the DAF-2 signaling pathway mediates the metabolic and longevity effects of axenic culture medium. We show that both interventions act either antagonistically or in concert, depending on the parameter examined and that axenic culture medium, unlike DAF-2 signaling, does not need DAF-16 for generating these effects. In addition, we provide evidence that DAF-2 signaling controls mitochondrial bioenergetics by adjusting the rate of ATP synthesis to the rate of ATP utilization and by regulating the heat-producing proton leak pathway.
Houthoofd
Koen
K
Department of Biology, Ghent University, K.L. Ledeganckstraat 35, B-9000 Ghent, Belgium.
Braeckman
Bart P
BP
Lenaerts
Isabelle
I
Brys
Kristel
K
Matthijssens
Filip
F
De Vreese
Annemie
A
Van Eygen
Sylvie
S
Vanfleteren
Jacques R
JR
D000255:Adenosine Triphosphate / Q000378:metabolism; D000367:Age Factors; D000375:Aging / Q000378:metabolism*; D000818:Animals; D017173:Caenorhabditis elegans / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins; D002153:Calorimetry, Indirect / Q000379:methods; D015331:Cohort Studies; D005260:Female; D005508:Food Deprivation / Q000502:physiology*; D005856:Germ-Free Life; D008062:Lipofuscin / Q000378:metabolism; D008136:Longevity / Q000502:physiology; D008297:Male; D009154:Mutation; D010101:Oxygen Consumption; D011972:Receptor, Insulin / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction / Q000235:genetics*; D013696:Temperature; D013778:Tetrazolium Salts / Q000378:metabolism
D029742:Caenorhabditis elegans Proteins; D008062:Lipofuscin; D013778:Tetrazolium Salts; C059087:2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-5-((phenylamino)carbonyl)-2H-tetrazolium hydroxide; D000255:Adenosine Triphosphate; C107483:DAF-2 protein, C elegans; D011972:Receptor, Insulin