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 fibers. The same programmed deficits in muscle structure and function are found in numerous neurodegenerative syndromes and disease-related cachexia. 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.
Pubmed ID: 11175789 RIS Download
Animals | Cachexia | Cell Aging | DNA-Binding Proteins | GATA2 Transcription Factor | Hypertrophy | Insulin-Like Growth Factor I | Mice | Mice, Transgenic | Muscle, Skeletal | Neurodegenerative Diseases | Organ Size | Protein Isoforms | Regeneration | Tissue Distribution | Transcription Factors