The GH/IGF1 axis and signaling pathways in the muscle and bone: mechanisms underlying age-related skeletal muscle wasting and osteoporosis
Open accessAbstract
The widespread increase in life expectancy is accompanied by an increased prevalence of features of physical frailty. Signs and symptoms may include sarcopenia and osteopenia, reduced exercise capacity, and diminished sense of well-being. The pathogenesis of age-associated sarcopenia and osteopenia is multifactorial, and hormonal decline may be a contributing factor. Aging is associated with a progressive decrease in GH secretion, and more than 30% of elderly people have circulating IGF1 levels below the normal range found in the young. GH acts directly on target tissues, including skeletal muscle and bone among many others, but many effects are mediated indirectly by circulating (liver-derived) or locally produced IGF1. Aging is also associated with reduced insulin sensitivity which, in turn, may contribute to the impairment of IGF1 action. Recent experimental evidence suggests that besides the age-dependent decline in GH and IGF1 serum levels, the dysregulation of GH and IGF1 actions due to impairment of the post-receptor signaling machinery may contribute to the loss of muscle mass and osteopenia. This article will focus on the molecular mechanisms of impaired GH and IGF1 signaling and action in aging, and their role in the pathogenesis of sarcopenia and osteoporosis.
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Increased adiposity and circulating free fatty acids inhibit GH production and decrease plasma IGF-1 concentrations.
“Increased adiposity and circulating concentrations of free fatty acids inhibit GH production and decrease plasma concentrations of IGF-1.”
From Age-related and disease-related muscle loss: The effect of diabetes, obesity, and other diseases (2014) · cites this paper as [93]
A decrease in IGF-1 is associated with decreased muscle size and strength, decreased protein synthesis, and increased cell death, which in turn leads to increased visceral fat and decreased lean body mass.
“This decrease in IGF-1 is associated with decreased muscle size and strength, decreased protein synthesis, and increased cell death,93 which in turn leads to increased visceral fat and decreased lean body mass.94”
From Age-related and disease-related muscle loss: The effect of diabetes, obesity, and other diseases (2014) · cites this paper as [93]
GH acts both directly on bones and indirectly through liver-derived IGF-1 or locally produced IGF-1.
“GH acts both directly on bones and indirectly through liver-derived IGF-1 or locally produced IGF-1 [47].”
From Emerging role of liver-bone axis in osteoporosis (2024) · cites this paper as [47]
The GH-IGF-1 axis is involved in bone remodeling and metabolism and has an essential role in the achievement and maintenance of bone mass throughout life.
“The growth hormone (GH)-IGF-1 axis is also involved in bone remodeling and metabolism and has an essential role in the achievement and maintenance of bone mass throughout life.”
From Emerging role of liver-bone axis in osteoporosis (2024) · cites this paper as [47]
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- Authors
- Perrini, S., Laviola, L., Carreira, M. C., Cignarelli, A., Natalicchio, A., & Giorgino, F.
- Affiliations
- University of Bari Aldo Moro (IT)
- ORCID
- Venue
- Journal of Endocrinology
- Publisher
- Bioscientifica
- Published
- 2010-03-02
- Volume
- 205
- Issue
- 3
- Pages
- 201-210
- ISSN
- 0022-0795 (ISSN-L)
- 1479-6805
- OpenAlex
- W2132915404
- Cited by
- 317
- References
- 112
- Citations by year
- 2026: 8 · 2025: 11 · 2024: 13 · 2023: 12 · 2022: 17 · 2021: 18 · 2020: 14 · 2019: 15 · 2018: 23 · 2017: 17 · 2016: 25 · 2015: 23 · 2014: 29 · 2013: 27 · 2012: 36
- FWCI
- 4.19
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- CINECA IRIS Institutional Research Information System (University of Bari Aldo Moro) (submittedVersion)
- INFM-OAR (INFN Catania) (submittedVersion, other-oa)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Growth Hormone and Insulin-like Growth Factors
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Health Sciences › Medicine › Physiology › Nutrition and Health in Aging
- Keywords
- growth hormone, insulin-like growth factor I, somatotropic axis, sarcopenia, osteoporosis, osteopenia, aging, muscle atrophy, bone loss, insulin resistance, post-receptor signaling, frailty, skeletal muscle, bone
- MeSH terms
- Animals, Bone and Bones, Disease Models, Animal, Humans, Insulin-Like Growth Factor I, Osteoporosis, Growth Hormone, Signal Transduction, Muscle, Skeletal, Sarcopenia
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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