title: C. elegans S6K Mutants Require a Creatine-Kinase-like Effector for Lifespan Extension.
abstract: Deficiency of S6 kinase (S6K) extends the lifespan of multiple species, but the underlying mechanisms are unclear. To discover potential effectors of S6K-mediated longevity, we performed a proteomics analysis of long-lived rsks-1/S6K C. elegans mutants compared to wild-type animals. We identified the arginine kinase ARGK-1 as the most significantly enriched protein in rsks-1/S6K mutants. ARGK-1 is an ortholog of mammalian creatine kinase, which maintains cellular ATP levels. We found that argk-1 is possibly a selective effector of rsks-1/S6K-mediated longevity and that overexpression of ARGK-1 extends C. elegans lifespan, in part by activating the energy sensor AAK-2/AMPK. argk-1 is also required for the reduced body size and increased stress resistance observed in rsks-1/S6K mutants. Finally, creatine kinase levels are increased in the brains of S6K1 knockout mice. Our study identifies ARGK-1 as a longevity effector in C. elegans with reduced RSKS-1/S6K levels.
authors.affiliation: Development, Aging and Regeneration Program, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USA; Graduate School of Biomedical Sciences, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USA.
authors.forename: Philip R
authors.initials: PR
authors.lastname: McQuary
authors.affiliation: The Buck Institute for Research on Aging, Novato, CA 94945, USA.
authors.forename: Chen-Yu
authors.initials: CY
authors.lastname: Liao
authors.affiliation: Development, Aging and Regeneration Program, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USA.
authors.forename: Jessica T
authors.initials: JT
authors.lastname: Chang
authors.affiliation: Development, Aging and Regeneration Program, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USA.
authors.forename: Caroline
authors.initials: C
authors.lastname: Kumsta
authors.affiliation: Development, Aging and Regeneration Program, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USA.
authors.forename: Xingyu
authors.initials: X
authors.lastname: She
authors.affiliation: Development, Aging and Regeneration Program, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USA.
authors.forename: Andrew
authors.initials: A
authors.lastname: Davis
authors.affiliation: Development, Aging and Regeneration Program, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USA.
authors.forename: Chu-Chiao
authors.initials: CC
authors.lastname: Chu
authors.affiliation: Development, Aging and Regeneration Program, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USA; Graduate School of Biomedical Sciences, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USA.
authors.forename: Sara
authors.initials: S
authors.lastname: Gelino
authors.affiliation: The Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: Rafael L
authors.initials: RL
authors.lastname: Gomez-Amaro
authors.affiliation: The Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Petrascheck
authors.affiliation: Proteomics Facility, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USA.
authors.forename: Laurence M
authors.initials: LM
authors.lastname: Brill
authors.affiliation: Department of Comparative Medicine, University of Washington, Seattle, WA 98034, USA.
authors.forename: Warren C
authors.initials: WC
authors.lastname: Ladiges
authors.affiliation: The Buck Institute for Research on Aging, Novato, CA 94945, USA.
authors.forename: Brian K
authors.initials: BK
authors.lastname: Kennedy
authors.affiliation: Development, Aging and Regeneration Program, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USA. Electronic address: mhansen@sbpdiscovery.org.
authors.forename: Malene
authors.initials: M
authors.lastname: Hansen
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000818:Animals; D001122:Arginine Kinase / Q000502:physiology*; D017173:Caenorhabditis elegans / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism / Q000502:physiology*; D003402:Creatine Kinase / Q000502:physiology*; D004789:Enzyme Activation; D005260:Female; D008136:Longevity; D008297:Male; D018345:Mice, Knockout; D009457:Neuroglia / Q000201:enzymology; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000502:physiology*
chemical_list: D029742:Caenorhabditis elegans Proteins; D017346:Protein Serine-Threonine Kinases; D038762:Ribosomal Protein S6 Kinases, 70-kDa; C510541:AAK-2 protein, C elegans; D055372:AMP-Activated Protein Kinases; D003402:Creatine Kinase; C000612725:ARGK-1 protein, C elegans; D001122:Arginine Kinase