ArticleAging cell2021
The antagonistic pleiotropy of insulin-like growth factor 1.
Article in Aging cell, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
47 citing papers in PubMed, 59 citations in OpenAlex.
- Lifestyle intervention based on aerobic exercise and Mediterranean diet modulates IGF-1 and its binding proteins in breast cancer survivors.Breast cancer research : BCR · 2026Trial
- [The unbearable versatility of endocrine aging].Problemy endokrinologii · 2026Review
- Examining the role of insulin-like growth factor 1 in the pathophysiology of carpal tunnel syndrome: a Mendelian randomization study.International journal of epidemiology · 2026Article
- From Athletic Performance to Functional Ageing: Shared Genetic Architecture, Redox-Inflammatory Pathways and Functional Reserve Across the Life Course-A Narrative Review.Biomedicines · 2026Review
- Small-molecule IGF1R inhibitors extend healthspan in a mouse model.bioRxiv : the preprint server for biology · 2026Article
- Molecular mechanisms of metformin action: From metabolic effects to lifespan extension and healthspan promotion.Journal of medical biochemistry · 2026Article
- Parallel Selection for Longevity in Mammals and Birds.bioRxiv : the preprint server for biology · 2025Article
- Reduced IGF-1 signaling fails to limit Alzheimer's disease progression in a novel rat model of IGF-1R haploinsufficiency.Scientific reports · 2025Article
- Growing Pains: GH-induced Fibrosis Across Multiple Organs in bGH Mice.Endocrinology · 2025Article
- The Power of Exercise: Unlocking the Biological Mysteries of Peripheral-Central Crosstalk in Parkinson's Disease.Journal of advanced research · 2025Review
- Long-Term Obesity and Biological Aging in Young Adults.JAMA network open · 2025Article
- Review
- Identification of functional rare coding variants in IGF-1 gene in humans with exceptional longevity.Scientific reports · 2025Article
- The vasoprotective role of IGF-1 signaling in the cerebral microcirculation: prevention of cerebral microhemorrhages in aging.GeroScience · 2025Review
- An evolutionary medicine and life history perspective on aging and disease: Trade-offs, hyperfunction, and mismatch.Evolution, medicine, and public health · 2025Review
- Geroscience in heart failure: the search for therapeutic targets in the shared pathobiology of human aging and heart failure.The journal of cardiovascular aging · 2025Article
- Aging and IGF-I: relationships with vitamin D and body composition. A mediation analysis.Frontiers in nutrition · 2025Article
- Intranasal long R3 insulin-like growth factor-1 treatment promotes amyloid plaque remodeling in cerebral cortex but fails to preserve cognitive function in male 5XFAD mice.Journal of Alzheimer's disease : JAD · 2025Article
- MEG8 as an antagonistic pleiotropic mechanism in breast cancer.Cell death discovery · 2024Article
- Association between prescription drugs and all-cause mortality risk in the UK population.Aging cell · 2024Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
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. 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. These data suggest that IGF-1 signaling could be harmful in older adults, who may actually benefit from the attenuation of biological growth pathways.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.