The somatotropic axis in human aging: framework for the current state of knowledge and future research
Open accessAbstract
Mutations resulting in reduced signaling of the growth hormone/insulin-like growth factor-1 (GH/IGF-1) axis are associated with increased life- and healthspan across model organisms. Similar findings have been noted in human cohorts with functional mutations in the somatotropic axis, suggesting that this pathway may also be relevant to human aging and protection from age-related diseases. While epidemiological data indicate that low circulating IGF-1 level may protect aging populations from cancer, results remain inconclusive regarding most other diseases. We propose that studies in humans and animals need to consider differences in sex, pathway function, organs, and time-specific effects of GH/IGF-1 signaling in order to better define the role of the somatotropic axis in aging. Agents that modulate signaling of the GH/IGF-1 pathway are available for human use, but before they can be implemented in clinical studies that target aging and age-related diseases, researchers need to address the challenges discussed in this Review.
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Human studies suggest attenuation of the GH/IGF-1 axis may protect from age-related conditions, despite inconsistencies in directionality.
“a number of human studies suggest that its attenuation may protect from age-related conditions”
From Benefits of Metformin in Attenuating the Hallmarks of Aging (2020) · cites this paper as Milman et al. 2016
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“Standing out in this list are Bmpr2 (ligands: BMP7 and GDF9), Ifnar1 (ligand: IFNA10), Igf1r (ligands: CDH1, GPC3, and INS), all of which have been implicated in organismal longevity and brain aging and whose plasma ligands similarly change with age (Katsimpardi et al., 2014; Kimura et al., 1997; Loffredo et al., 2013…”
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Regulation of Growth Hormone Secretion
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Self-citationAging and IGF-I: relationships with vitamin D and body composition. A mediation analysis
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- Authors
- Milman, S., Huffman, D. M., & Barzilai, N.
- Affiliations
- Albert Einstein College of Medicine (US)
- Corresponding author
- Milman, Sofiya
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2016-06
- Volume
- 23
- Issue
- 6
- Pages
- 980-989
- ISSN
- 1550-4131 (ISSN-L)
- PMC
- PMC4919980
- OpenAlex
- W2424236546
- Cited by
- 150
- References
- 125
- Citations by year
- 2026: 10 · 2025: 10 · 2024: 13 · 2023: 17 · 2022: 22 · 2021: 17 · 2020: 15 · 2019: 15 · 2018: 15 · 2017: 14 · 2016: 1
- FWCI
- 2.20
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- American Federation for Aging Research (R00AG037574)
- National Institutes of Health (P01AG021654, R37 AG18381)
- National Institute on Aging (1 R01AG044829)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Growth Hormone and Insulin-like Growth Factors
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Keywords
- somatotropic axis, growth hormone, insulin-like growth factor I, aging, healthspan, life expectancy, IGF-1 signaling, age-related diseases, cancer protection, sex differences, growth hormone therapy
- MeSH terms
- Aging, Disease, Humans, Insulin-Like Growth Factor I, Research, Growth Hormone, Signal Transduction
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