The AMP-activated protein kinase AAK-2 links energy levels and insulin-like signals to lifespan in C. elegans.
Although limiting energy availability extends lifespan in many organisms, it is not understood how lifespan is coupled to energy levels. We find that the AMP:ATP ratio, a measure of energy levels, increases with age in Caenorhabditis elegans and can be used to predict life expectancy. The C. elegans AMP-activated protein kinase alpha subunit AAK-2 is activated by AMP and functions to extend lifespan. In addition, either an environmental stressor that increases the AMP:ATP ratio or mutations that lower insulin-like signaling extend lifespan in an aak-2-dependent manner. Thus, AAK-2 is a sensor that couples lifespan to information about energy levels and insulin-like signals.
Apfeld
Javier
J
Elixir Pharmaceuticals, Cambridge, Massachusetts 02139, USA. japfeld@elixirpharm.com
O'Connor
Greg
G
McDonagh
Tom
T
DiStefano
Peter S
PS
Curtis
Rory
R
D055372:AMP-Activated Protein Kinases; D000249:Adenosine Monophosphate / Q000378:metabolism*; D000255:Adenosine Triphosphate / Q000378:metabolism; D000367:Age Factors; D000375:Aging / Q000502:physiology*; D000818:Animals; D030801:Animals, Genetically Modified; D017173:Caenorhabditis elegans / Q000502:physiology*; D003433:Crosses, Genetic; D017931:DNA Primers; D004734:Energy Metabolism / Q000502:physiology; D018014:Gene Transfer Techniques; D049452:Green Fluorescent Proteins; D047468:Immunoprecipitation; D007328:Insulin / Q000378:metabolism; D008136:Longevity / Q000187:drug effects*; D009097:Multienzyme Complexes / Q000235:genetics / Q000378:metabolism*; D016296:Mutagenesis; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D017422:Sequence Analysis, DNA; D015398:Signal Transduction / Q000502:physiology*; D013696:Temperature
D017931:DNA Primers; D007328:Insulin; D009097:Multienzyme Complexes; D049452:Green Fluorescent Proteins; D000249:Adenosine Monophosphate; D000255:Adenosine Triphosphate; D017346:Protein Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases