Modifications in the myogenic program induced by in vivo and in vitro aging.
In this study, we have used high density cDNA arrays to assess age-related changes in gene expression in the myogenic program of human satellite cells and to elucidate modifications in differentiation capacity that could occur throughout in vitro cellular aging. We have screened a collection of 2016 clones from a human skeletal muscle 3'-end cDNA library in order to investigate variations in the myogenic program of myotubes formed by the differentiation of myoblasts of individuals with different ages (5 days old, 52 years old and 79 years old) and induced to differentiate at different stages of their lifespan (early proliferation, presenescence and senescence). Although our analysis has not been able to underline specific changes in the expression of genes encoding proteins involved in muscle structure and/or function, we have demonstrated an age-related induction of genes involved in stress response and a down-regulation of genes involved both in mitochondrial electron transport/ATP synthase and in glycolysis/TCA cycle. From this global approach of post-mitotic cell aging, we have identified 2 potential new markers of presenescence for human myotubes, both strongly linked to carbohydrate metabolism, which could be useful in developing therapeutic strategies.
Bortoli
Sylvie
S
Genexpress, CNRS FRE 2571, 19 rue Guy Moquet, BP 8, 94801 Villejuif Cedex, France.
Renault
Valérie
V
Mariage-Samson
Régine
R
Eveno
Eric
E
Auffray
Charles
C
Butler-Browne
Gill
G
Piétu
Geneviève
G
D000368:Aged; D000375:Aging / Q000235:genetics / Q000502:physiology*; D050260:Carbohydrate Metabolism; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology; D049109:Cell Proliferation; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000235:genetics / Q000502:physiology*; D002675:Child, Preschool; D002952:Citric Acid Cycle / Q000235:genetics / Q000502:physiology; D004579:Electron Transport / Q000235:genetics / Q000502:physiology; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000235:genetics / Q000502:physiology*; D006019:Glycolysis / Q000235:genetics / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D008931:Mitochondria, Muscle / Q000235:genetics / Q000378:metabolism; D025261:Mitochondrial Proton-Translocating ATPases / Q000235:genetics / Q000378:metabolism; D024510:Muscle Development / Q000235:genetics / Q000502:physiology*; D018485:Muscle Fibers, Skeletal / Q000378:metabolism; D018482:Muscle, Skeletal / Q000502:physiology*; D020411:Oligonucleotide Array Sequence Analysis; D032496:Satellite Cells, Skeletal Muscle / Q000502:physiology*
D025261:Mitochondrial Proton-Translocating ATPases