title: Impaired energy metabolism of senescent muscle satellite cells is associated with oxidative modifications of glycolytic enzymes.
abstract: Accumulation of oxidized proteins is a hallmark of cellular and organismal aging. Adult muscle stem cell (or satellite cell) replication and differentiation is compromised with age contributing to sarcopenia. However, the molecular events related to satellite cell dysfunction during aging are not completely understood. In the present study we have addressed the potential impact of oxidatively modified proteins on the altered metabolism of senescent human satellite cells. By using a modified proteomics analysis we have found that proteins involved in protein quality control and glycolytic enzymes are the main targets of oxidation (carbonylation) and modification with advanced glycation/lipid peroxidation end products during the replicative senescence of satellite cells. Inactivation of the proteasome appeared to be a likely contributor to the accumulation of such damaged proteins. Metabolic and functional analyses revealed an impaired glucose metabolism in senescent cells. A metabolic shift leading to increased mobilization of non-carbohydrate substrates such as branched chain amino acids or long chain fatty acids was observed. Increased levels of acyl-carnitines indicated an increased turnover of storage and membrane lipids for energy production. Taken together, these results support a link between oxidative protein modifications and the altered cellular metabolism associated with the senescent phenotype of human myoblasts.
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, UMR 8256, Biological Adaptation and Ageing- IBPS, CNRS UMR 8256, INSERM U1164, Paris, France.
authors.forename: Martín A
authors.initials: MA
authors.lastname: Baraibar
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, UMR 8256, Biological Adaptation and Ageing- IBPS, CNRS UMR 8256, INSERM U1164, Paris, France.
authors.forename: Janek
authors.initials: J
authors.lastname: Hyzewicz
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Southern Denmark, Odense, Denmark.
authors.forename: Adelina
authors.initials: A
authors.lastname: Rogowska-Wrzesinska
authors.affiliation: Université Paris Descartes, Sorbonne Paris Cité, Faculté de Médecine, INSERM U1016, CNRS UMR 8104, Institut Cochin, Paris, France.
authors.forename: Anne-Laure
authors.initials: AL
authors.lastname: Bulteau
authors.affiliation: Université Paris Descartes, Sorbonne Paris Cité, Faculté de Médecine, INSERM U1016, CNRS UMR 8104, Institut Cochin, Paris, France.
authors.forename: Carina
authors.initials: C
authors.lastname: Prip-Buus
authors.affiliation: Institut de Myologie, UPMC Univ Paris 06, UMRS INSERM U974, CNRS UMR 7215, CHU Pitié-Salpétrière, Sorbonne Universités, Paris, France.
authors.forename: Gillian
authors.initials: G
authors.lastname: Butler-Browne
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, UMR 8256, Biological Adaptation and Ageing- IBPS, CNRS UMR 8256, INSERM U1164, Paris, France.
authors.forename: Bertrand
authors.initials: B
authors.lastname: Friguet
mesh_terms: D002478:Cells, Cultured; D015180:Electrophoresis, Gel, Two-Dimensional; D004734:Energy Metabolism / Q000502:physiology*; D006019:Glycolysis / Q000502:physiology*; D006801:Humans; D018384:Oxidative Stress; D050050:Protein Carbonylation; D032496:Satellite Cells, Skeletal Muscle / Q000502:physiology*
keywords: aging; cellular senescence; energy metabolism; myoblasts; protein oxidation; proteostasis