The DOI matches its Crossref record; 30 of the 30 references it cites were found in a registry or an index.
IGF-1 receptor regulates lifespan and resistance to oxidative stress in mice
Open accessAbstract
Studies in invertebrates have led to the identification of a number of genes that regulate lifespan, some of which encode components of the insulin or insulin-like signalling pathways. Examples include the related tyrosine kinase receptors InR (Drosophila melanogaster) and DAF-2 (Caenorhabditis elegans) that are homologues of the mammalian insulin-like growth factor type 1 receptor (IGF-1R). To investigate whether IGF-1R also controls longevity in mammals, we inactivated the IGF-1R gene in mice (Igf1r). Here, using heterozygous knockout mice because null mutants are not viable, we report that Igf1r(+/-) mice live on average 26% longer than their wild-type littermates (P < 0.02). Female Igf1r(+/-) mice live 33% longer than wild-type females (P < 0.001), whereas the equivalent male mice show an increase in lifespan of 16%, which is not statistically significant. Long-lived Igf1r(+/-) mice do not develop dwarfism, their energy metabolism is normal, and their nutrient uptake, physical activity, fertility and reproduction are unaffected. The Igf1r(+/-) mice display greater resistance to oxidative stress, a known determinant of ageing. These results indicate that the IGF-1 receptor may be a central regulator of mammalian lifespan.
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“Nutrient sensing and energy homeostasis have been implicated as connecting mitochondrial function and longevity104,105.”
From Stem cell aging: mechanisms, regulators and therapeutic opportunities (2014) · cites this paper as [105]
In the citing paper
“Mutations that decrease IGF1 levels or activity cause reduced growth and longer life in mice by up to 65% (Coschigano et al., 2000; Holzenberger et al., 2003).”
From The Search for Antiaging Interventions: From Elixirs to Fasting Regimens (2014) · cites this paper as Holzenberger et al., 2003
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Metadata
- Authors
- Holzenberger, M., Dupont, J., Ducos, B., Leneuve, P., Géloën, A., Even, P. C., Cervera, P., & Le Bouc, Y.
- Affiliations
- Inserm (FR)
- Physiologie de la Reproduction et des Comportements (FR)
- Institut National de Recherche pour l'Agriculture, l'Alimentation et l'Environnement (FR)
- Hôpital Saint-Antoine (FR)
- Corresponding author
- Holzenberger, Martin
- ORCID
- Venue
- Nature
- Published
- 2002-12-04
- Volume
- 421
- Issue
- 6919
- Pages
- 182-187
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W1985425785
- Cited by
- 2,109
- References
- 30
- Citations by year
- 2026: 32 · 2025: 41 · 2024: 56 · 2023: 61 · 2022: 84 · 2021: 87 · 2020: 81 · 2019: 73 · 2018: 59 · 2017: 82 · 2016: 84 · 2015: 91 · 2014: 86 · 2013: 87 · 2012: 99
- FWCI
- 29.68
- Type
- journal article
- Language
- en
- Open access
- Licence
- other-oa
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion, other-oa)
- HAL (submittedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Growth Hormone and Insulin-like Growth Factors
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Keywords
- IGF-1 receptor, lifespan, longevity, oxidative stress resistance, insulin receptor, daf-2, international normalized ratio, heterozygous knockout mice, aging, sex differences in longevity
- MeSH terms
- Aging, Animals, Blood Glucose, Cells, Cultured, Female, Fertility, Fibroblasts, Glucose Tolerance Test, Ligands, Longevity, Male, Phenotype, Sexual Maturation, Signal Transduction, Gene Deletion, Receptor, IGF Type 1, Mice, Knockout, Oxidative Stress, Mice
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