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The antagonistic pleiotropy of insulin-like growth factor 1
Zhang WB, Ye K, Barzilai N, Milman S.. Aging cell, 2021-08-07
Topic: Brain proteins, microglia and lab models
While insulin-like growth factor-1 (IGF-1) is a well-established modulator of aging and longevity in model organisms, its role in humans has been controversial. In this study, we used the UK Biobank (n = 440,185) to resolve previous ambiguities in the relationship between serum IGF-1 levels and clinical disease. We examined prospective associations of serum IGF-1 with mortality, dementia, vascular disease, diabetes, osteoporosis, and cancer, finding two generalized patterns: First, IGF-1 interacts with age to modify risk in a manner consistent with antagonistic pleiotropy; younger individuals with high IGF-1 are protected from disease, while older individuals with high IGF-1 are at increased risk for incident disease or death.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Zhang, W. B., Ye, K., Barzilai, N., & Milman, S. (2021). The antagonistic pleiotropy of insulin-like growth factor 1. Aging cell. https://doi.org/10.1111/acel.13443
Vancouver
Zhang WB, Ye K, Barzilai N, Milman S. The antagonistic pleiotropy of insulin-like growth factor 1. Aging cell. 2021. doi:10.1111/acel.13443. PMID: 34363732.
BibTeX
@article{zhang2021-34363732,
author = {Zhang, W. B. and Ye, K. and Barzilai, N. and Milman, S.},
title = {{The antagonistic pleiotropy of insulin-like growth factor 1}},
journal = {Aging cell},
year = {2021},
doi = {10.1111/acel.13443},
pmid = {34363732},
url = {https://doi.org/10.1111/acel.13443}
}
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. Check the citation against the original before you use it.
Key findings
- In this study, we used the UK Biobank (n = 440,185) to resolve previous ambiguities in the relationship between serum IGF-1 levels and clinical disease.
- We examined prospective associations of serum IGF-1 with mortality, dementia, vascular disease, diabetes, osteoporosis, and cancer, finding two generalized patterns: First, IGF-1 interacts with age to modify risk in a manner consistent with antagonistic pleiotropy; younger individuals with high IGF-1 are protected from disease, while older individuals with high IGF-1 are at increased risk for incident disease or death.
- Second, the association between IGF-1 and risk is generally U-shaped, indicating that both high and low levels of IGF-1 may be detrimental.
- With the exception of a more uniformly positive relationship between IGF-1 and cancer, these effects were remarkably consistent across a wide range of conditions, providing evidence for a unifying pathway that determines risk for most age-associated diseases.
Why it matters
Using UK Biobank data from 440,185 people, this study found that high insulin-like growth factor 1 was linked to lower disease risk in younger people but higher risk of disease or death, including dementia, in older people. It describes risk patterns only and does not test any treatment, cure, or prevention.
Study details
- Participants440,185
- Evidence strengthLow
How this study scored 51/100
Published in a peer-reviewed journal. Scored zero for study design, effect reported and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Aging cell) |
| Journal's citation record | 2 / 4 | Aging Cell: journal h-index 216 (OpenAlex, 2026-10-29) |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 3 / 5 | 2021 — within 6 year(s) of the newest study here |
| Sample size | 4 / 4 | 440,185 participants |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 4 / 7 | Cited 63 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 9.0 citations a year over 7 year(s) since 2021 |
| Impact for its field and year | 3 / 6 | Cited 6.6× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 0 / 6 | No other study in this library cites it |
| Still being cited | 2 / 4 | Cited 34 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author Sofiya Milman: h-index 28 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | University of Chicago: institution h-index 1,769 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 2 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 34363732) |
| Free to read | 2 / 2 | Free to read |
| Total | 51 / 100 | — |
What each of these 20 components measures, and what this score is not →
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Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
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