title: Human myotubes from myoblast cultures undergoing senescence exhibit defects in glucose and lipid metabolism.
abstract: Adult stem cells are known to have a finite replication potential. Muscle biopsy-derived human satellite cells (SCs) were grown at different passages and differentiated to human myotubes in culture to analyze the functional state of various carbohydrate and lipid metabolic pathways. As the proliferative potential of myoblasts decreased dramatically with passage number, a number of cellular functions were altered: the capacity of myoblasts to fuse and differentiate into myotubes was reduced, and metabolic processes in myotubes such as glucose uptake, glycogen synthesis, glucose oxidation and fatty acid β-oxidation became gradually impaired. Upon insulin stimulation, glucose uptake and glycogen synthesis increased but as the cellular proliferative capacity became gradually exhausted, the response dropped concomitantly. Palmitic acid incorporation into lipids in myotubes decreased with passage number and could be explained by reduced incorporation into diacyl- and triacylglycerols. The levels of long-chain acyl-CoA esters decreased with increased passage number. Late-passage, non-proliferating, myoblast cultures showed strong senescence-associated β-galactosidase activity indicating that the observed metabolic defects accompany the induction of a senescent state. The main function of SCs is regeneration and skeletal muscle-build up. Thus, the metabolic defects observed during aging of SC-derived myotubes could have a role in sarcopenia, the gradual age-related loss of muscle mass and strength.
authors.affiliation: Center for Stem Cell Treatment, Department of Clinical Immunology, Odense University Hospital & University of Southern Denmark, Odense, Denmark. jnehlin@health.sdu.dk
authors.forename: Jan O
authors.initials: JO
authors.lastname: Nehlin
authors.forename: Marlene
authors.initials: M
authors.lastname: Just
authors.forename: Arild C
authors.initials: AC
authors.lastname: Rustan
authors.forename: Michael
authors.initials: M
authors.lastname: Gaster
mesh_terms: D000214:Acyl Coenzyme A / Q000378:metabolism; D053687:Adult Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D002454:Cell Differentiation; D002459:Cell Fusion; D049109:Cell Proliferation; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000502:physiology*; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000494:pharmacology; D050356:Lipid Metabolism / Q000187:drug effects; D018485:Muscle Fibers, Skeletal / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D032446:Myoblasts / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D019308:Palmitic Acid / Q000378:metabolism; D032496:Satellite Cells, Skeletal Muscle / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D001616:beta-Galactosidase / Q000378:metabolism
chemical_list: D000214:Acyl Coenzyme A; D007328:Insulin; D019308:Palmitic Acid; D001616:beta-Galactosidase; D005947:Glucose