title: The AMP-activated protein kinase AAK-2 links energy levels and insulin-like signals to lifespan in C. elegans.
abstract: 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.
authors.affiliation: Elixir Pharmaceuticals, Cambridge, Massachusetts 02139, USA. japfeld@elixirpharm.com
authors.forename: Javier
authors.initials: J
authors.lastname: Apfeld
authors.forename: Greg
authors.initials: G
authors.lastname: O'Connor
authors.forename: Tom
authors.initials: T
authors.lastname: McDonagh
authors.forename: Peter S
authors.initials: PS
authors.lastname: DiStefano
authors.forename: Rory
authors.initials: R
authors.lastname: Curtis
mesh_terms: 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
chemical_list: 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