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The effect of age on the skeletal muscle transcriptome during hypertrophy

ABSTRACT: Transcriptome analysis of skeletal muscle during hypertrophic growth in aged mice Global gene expression patterns were determined from microarray results on day 1, 3, 5, 7, 10 and 14 during plantaris muscle hypertrophy induced by synergist ablation in old adult mice (25 months).

ORGANISM(S): Mus musculus

PROVIDER: GSE67160 | GEO | 2015/06/01

SECONDARY ACCESSION(S): PRJNA279140

REPOSITORIES: GEO

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Expression data during plantaris muscle hypertrophy induced by synergist ablation in young adult mice

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Expression data during plantaris muscle hypertrophy induced by synergist ablation in young adult mice

Project description:Global gene expression patterns were determined from microarray results on day 1, 3, 5, 7, 10 and 14 during plantaris muscle hypertrophy induced by synergist ablation in young adult mice (5 months). For each time point, two Affymetrix chips (Mouse Gene 1.0 ST) were used with 100 ng of total RNA derived from a pooled sample of either the right or left plantaris muscles from six animals.

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Senolytics rescue blunted muscle hypertrophy in old mice

Project description:With aging, skeletal muscle plasticity is attenuated in response to exercise. Here, we report that senescent cells, identified using senescence markers senescence-associated β-Galactosidase (SA β-Gal) and p21 are very infrequent in resting muscle but emerge approximately two-weeks after a bout of resistance exercise in humans. We hypothesized that these cells contribute to blunted hypertrophic potential in old age. Using synergist ablation-induced mechanical overload of the plantaris muscle to model resistance training in adult (5-6 month) and old (23-24 month) male C57BL/6J mice, we found increased senescent cells in both age groups during hypertrophy. Consistent with the human data, there were negligible senescent cells in adult and old sham controls, but old mice had significantly more senescent cells 7- and 14-days following overload relative to young. Old mice had blunted whole muscle hypertrophy when compared to adult mice, along with smaller muscle fibers, specifically glycolytic Type 2x+2b fibers. To ablate senescent cells using a hit-and-run approach, old mice were treated with vehicle or a senolytic cocktail consisting of 5 mg/kg dasatinib and 50 mg/kg quercetin (D+Q) on day 7 and 10 during 14-days of overload; control mice underwent sham surgery with or without senolytic treatment. Old mice given D+Q had larger muscles and muscle fibers after 14 days of overload, fewer senescent cells when compared to vehicle-treated old mice, and changes in the expression of genes (i.e., Igf1, Ddit4, Mmp14) that are associated with hypertrophic growth . Our data collectively show that senescent cells emerge in human and mouse skeletal muscle following a hypertrophic stimulus, and that D+Q improves muscle growth in old mice.

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Expression data during plantaris muscle hypertrophy with/without satellite cells induced by synergist ablation in young adult Pax7-DTA mice

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Targeted inhibition of platelet-derived growth factor signaling prevents muscle fiber growth during skeletal muscle hypertrophy

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