Cited by 1,137Muscle Physiology and DisordersNeurogenetic and Muscular Disorders ResearchGenetics and Physical Performance

Localized Igf-1 transgene expression sustains hypertrophy and regeneration in senescent skeletal muscle

Musarò, Antonio, McCullagh, Karl, Paul, Angelika, Houghton, Leslie, Dobrowolny, Gabriella, Molinaro, Mario, Barton, Elisabeth R., L Sweeney, H. +1 more·2001·Nature Genetics

Abstract

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.

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Crossref · 10.1038/84839

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  • Muscle-specific overexpression of a locally acting IGF1 isoform in mice showed that localized IGF1 expression sustains muscle growth and regeneration.

    “Muscle-specific overexpression of a locally acting IGF1 isoform in mice showed that localized IGF1 expression sustains muscle growth and regeneration6.”

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Authors
Musarò, A., McCullagh, K., Paul, A., Houghton, L., Dobrowolny, G., Molinaro, M., Barton, E. R., L Sweeney, H., & Rosenthal, N.
Affiliations
  • Massachusetts General Hospital (US)
  • Sapienza University of Rome (IT)
  • University of Pennsylvania (US)
Corresponding author
Rosenthal, Nadia
Venue
Nature Genetics
Published
2001-02
Volume
27
Issue
2
Pages
195-200
ISSN
  • 1061-4036 (ISSN-L)
  • 1546-1718
OpenAlex
W1562705858
Cited by
1,137
References
30
Citations by year
2026: 17 · 2025: 19 · 2024: 27 · 2023: 22 · 2022: 21 · 2021: 27 · 2020: 29 · 2019: 35 · 2018: 38 · 2017: 28 · 2016: 34 · 2015: 60 · 2014: 52 · 2013: 59 · 2012: 71
FWCI
17.57
Type
journal article
Language
en
Open access
closed
Locations
  • Nature Genetics (publishedVersion)
  • PubMed (publishedVersion)
  • IRIS Research product catalog (Sapienza University of Rome) (submittedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
  • Health Sciences › Medicine › Genetics › Neurogenetic and Muscular Disorders Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Physical Performance
Keywords
insulin-like growth factor I, skeletal muscle aging, muscle atrophy, myocyte hypertrophy, muscle regeneration, muscle fibrosis, GATA2, transgenic mouse model, muscle strength
MeSH terms
Animals, Cachexia, DNA-Binding Proteins, Hypertrophy, Insulin-Like Growth Factor I, Mice, Transgenic, Organ Size, Regeneration, Tissue Distribution, Transcription Factors, Cellular Senescence, Muscle, Skeletal, Neurodegenerative Diseases, Protein Isoforms, GATA2 Transcription Factor, Mice

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