Effects of IGF-1 isoforms on muscle growth and sarcopenia
Open accessAbstract
The decline in skeletal muscle mass and strength occurring in aging, referred as sarcopenia, is the result of many factors including an imbalance between protein synthesis and degradation, changes in metabolic/hormonal status, and in circulating levels of inflammatory mediators. Thus, factors that increase muscle mass and promote anabolic pathways might be of therapeutic benefit to counteract sarcopenia. Among these, the insulin-like growth factor-1 (IGF-1) has been implicated in many anabolic pathways in skeletal muscle. IGF-1 exists in different isoforms that might exert different role in skeletal muscle. Here we study the effects of two full propeptides IGF-1Ea and IGF-1Eb in skeletal muscle, with the aim to define whether and through which mechanisms their overexpression impacts muscle aging. We report that only IGF-1Ea expression promotes a pronounced hypertrophic phenotype in young mice, which is maintained in aged mice. Nevertheless, examination of aged transgenic mice revealed that the local expression of either IGF-1Ea or IGF-1Eb transgenes was protective against age-related loss of muscle mass and force. At molecular level, both isoforms activate the autophagy/lysosome system, normally altered during aging, and increase PGC1-α expression, modulating mitochondrial function, ROS detoxification, and the basal inflammatory state occurring at old age. Moreover, morphological integrity of neuromuscular junctions was maintained and preserved in both MLC/IGF-1Ea and MLC/IGF-1Eb mice during aging. These data suggest that IGF-1 is a promising therapeutic agent in staving off advancing muscle weakness.
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Among IGF1 isoforms, IGF-1Ea is the most powerful in increasing muscle mass and force both in young and aged mice.
“Among the different IGF1 isoforms, which differ in the N‐terminal signal peptide (Class 1 or 2) and the C‐terminal extension peptide (E‐peptide Ea or Eb), IGF-1Ea is the most powerful in increasing muscle mass and force both in young and aged mice7.”
From Mechanisms of muscle atrophy and hypertrophy: implications in health and disease (2021) · cites this paper as [7]
IGF-1 controls skeletal muscle anabolism and catabolism, exerting anabolic effects by regulating mitochondrial function, ROS detoxification, and the basal inflammatory state in aging individuals.
“IGF-1, a key factor controlling skeletal muscle anabolism and catabolism, exerts its anabolic effects on skeletal muscle by regulating mitochondrial function, ROS detoxification, and the basal inflammatory state in aging individuals [106].”
From Exerkines and Sarcopenia: Unveiling the Mechanism Behind Exercise-Induced Mitochondrial Homeostasis (2025) · cites this paper as [106]
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- Authors
- Ascenzi, F., Barberi, L., Dobrowolny, G., Villa Nova Bacurau, A., Nicoletti, C., Rizzuto, E., Rosenthal, N., Scicchitano, B. M., & Musarò, A.
- Affiliations
- Istituto Pasteur (IT)
- School of Physical Education and Sport University of São Paulo São Paulo Brazil
- Sapienza University of Rome (IT)
- Jackson Laboratory (US)
- Università Cattolica del Sacro Cuore (IT)
- Corresponding author
- Musarò, Antonio
- ORCID
- Venue
- Aging Cell
- Publisher
- Wiley
- Published
- 2019-04-05
- Volume
- 18
- Issue
- 3
- Pages
- e12954-e12954
- ISSN
- 1474-9718 (ISSN-L)
- 1474-9726
- PMC
- PMC6516183
- OpenAlex
- W2926702890
- Cited by
- 250
- References
- 39
- Citations by year
- 2026: 21 · 2025: 33 · 2024: 36 · 2023: 44 · 2022: 33 · 2021: 46 · 2020: 30 · 2019: 7
- FWCI
- 9.59
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Aging Cell (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- IRIS Research product catalog (Sapienza University of Rome) (submittedVersion, cc-by)
- The Mouseion at the JAXlibrary (Jackson Laboratory) (submittedVersion, cc-by)
- The Mouseion at the JAXlibrary (Jackson Laboratory) (submittedVersion)
- PubliCatt (Università Cattolica del Sacro Cuore) (submittedVersion, cc-by)
- Spiral (Imperial College London) (submittedVersion, cc-by)
- Funders
- Agenzia Spaziale Italiana
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Health Sciences › Medicine › Physiology › Nutrition and Health in Aging
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Growth Hormone and Insulin-like Growth Factors
- Keywords
- insulin-like growth factor I, sarcopenia, muscle aging, skeletal muscle hypertrophy, autophagy-lysosome system, PGC-1α, mitochondrial function, reactive oxygen species, inflammation, neuromuscular junction, muscle mass and strength, transgenic mice
- MeSH terms
- Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha, Aging, Animals, Inflammation, Insulin-Like Growth Factor I, Mice, Transgenic, Mitochondria, Neuromuscular Junction, Signal Transduction, Up-Regulation, Reactive Oxygen Species, Muscle, Skeletal, Protein Isoforms, Mice, Sarcopenia
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