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Pridružen/-a: 18.05. 2012, 19:47
Prispevkov: 747
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 Objavljeno: 13 Jan 2013 15:25 |
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Localized Igf-1 transgene expression sustains hypertrophy and regeneration in senescent skeletal muscle
Aging skeletal muscles suffer a steady decline in mass and functional performance, and compromised muscle integrity as fibrotic invasions replace contractile tissue, accompanied by a characteristic loss in the fastest, most powerful muscle fibers1, 2. The same programmed deficits in muscle structure and function are found in numerous neurodegenerative syndromes and disease-related cachexia3. We have generated a model of persistent, functional myocyte hypertrophy using a tissue-restricted transgene encoding a locally acting isoform of insulin-like growth factor-1 that is expressed in skeletal muscle (mIgf-1). Transgenic embryos developed normally, and postnatal increases in muscle mass and strength were not accompanied by the additional pathological changes seen in other Igf-1 transgenic models. Expression of GATA-2, a transcription factor normally undetected in skeletal muscle, marked hypertrophic myocytes that escaped age-related muscle atrophy and retained the proliferative response to muscle injury characteristic of younger animals. The preservation of muscle architecture and age-independent regenerative capacity through localized mIgf-1 transgene expression suggests clinical strategies for the treatment of age or disease-related muscle frailty.
Vir: http://www.nature.com/ng/journal/v27/n2/abs/ng0201_195.html |
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