ArticleAging cell2014
Longevity effect of IGF-1R(+/-) mutation depends on genetic background-specific receptor activation.
Article in Aging cell, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers.
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Who cites it
65 citing papers in PubMed, 95 citations in OpenAlex.
- Lifespan and Fecundity Impacts of Reduced Insulin Signalling Can Be Directed by Mito-Nuclear Epistasis in Drosophila.Aging cell · 2026Article
- Mutation in IR or IGF1R produces features of long-lived mice while maintaining metabolic health.JCI insight · 2025Article
- Reduced IGF-1 signaling fails to limit Alzheimer's disease progression in a novel rat model of IGF-1R haploinsufficiency.Scientific reports · 2025Article
- FOXO3a upregulates DNA repair activities by transcriptional activation of target genes and provides the resistance to gamma radiation and the extension of lifespan in mouse.Biogerontology · 2025Article
- The IGF System and Aging.Endocrine reviews · 2025Review
- Non-additive strong gene interactions cause striking differences in organ pathology and cytokine response in Leishmaniasis.Frontiers in immunology · 2025Article
- Distinct, common and synergistic effects of insulin and IGF-1 receptors on healthy murine ageing.Heliyon · 2024Article
- Article
- Longevity through diet restriction and immunity.BMB reports · 2023Review
- GDF11 and aging biology - controversies resolved and pending.The journal of cardiovascular aging · 2023Article
- Aging microenvironment and antitumor immunity for geriatric oncology: the landscape and future implications.Journal of hematology & oncology · 2023Review
- Dietary supplementation of clinically utilized PI3K p110α inhibitor extends the lifespan of male and female mice.Nature aging · 2023Article
- Insulin and aging - a disappointing relationship.Frontiers in endocrinology · 2023Review
- Genetic Disruption of KLF1 K74 SUMOylation in Hematopoietic System Promotes Healthy Longevity in Mice.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2022Article
- Growth Hormone, Not IGF-1 Is the Key Longevity Regulator in Mammals.The journals of gerontology. Series A, Biological sciences and medical sciences · 2022Article
- Fine-Tuning Cardiac Insulin-Like Growth Factor 1 Receptor Signaling to Promote Health and Longevity.Circulation · 2022Article
- Article
- Sexual dimorphic impact of adult-onset somatopause on life span and age-induced osteoarthritis.Aging cell · 2021Article
- Review
- Aging modulated by the Drosophila insulin receptor through distinct structure-defined mechanisms.Genetics · 2021Article
5 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Growth hormone (GH) and insulin-like growth factor (IGF) signaling regulates lifespan in mice. The modulating effects of genetic background gained much attention because it was shown that life-prolonging effects in Snell dwarf and GH receptor knockout vary between mouse strains. We previously reported that heterozygous IGF-1R inactivation (IGF-1R(+/-) ) extends lifespan in female mice on 129/SvPas background, but it remained unclear whether this mutation produces a similar effect in other genetic backgrounds and which molecules possibly modify this effect. Here, we measured the life-prolonging effect of IGF-1R(+/-) mutation in C57BL/6J background and investigated the role of insulin/IGF signaling molecules in strain-dependent differences. We found significant lifespan extension in female IGF-1R(+/-) mutants on C57BL/6J background, but the effect was smaller than in 129/SvPas, suggesting strain-specific penetrance of longevity phenotypes. Comparing GH/IGF pathways between wild-type 129/SvPas and C57BL/6J mice, we found that circulating IGF-I and activation of IGF-1R, IRS-1, and IRS-2 were markedly elevated in 129/SvPas, while activation of IGF pathways was constitutively low in spontaneously long-lived C57BL/6J mice. Importantly, we demonstrated that loss of one IGF-1R allele diminished the level of activated IGF-1R and IRS more profoundly and triggered stronger endocrine feedback in 129/SvPas background than in C57BL/6J. We also revealed that acute oxidative stress entails robust IGF-1R pathway activation, which could account for the fact that IGF-1R(+/-) stress resistance phenotypes are fully penetrant in both backgrounds. Together, these results provide a possible explanation why IGF-1R(+/-) was less efficient in extending lifespan in C57BL/6J compared with 129/SvPas.
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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.