Cited by 2,109Genetics, Aging, and Longevity in Model OrganismsGrowth Hormone and Insulin-like Growth FactorsMetabolism, Diabetes, and Cancer

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IGF-1 receptor regulates lifespan and resistance to oxidative stress in mice

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Holzenberger, Martin, Dupont, Joëlle, Ducos, Bertrand, Leneuve, Patricia, Géloën, Alain, Even, Patrick C., Cervera, Pascale, Le Bouc, Yves·2003·Nature

DOI 10.1038/nature01298

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Abstract

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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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: Holzenberger, Martin
Dupont, Joëlle
Ducos, Bertrand
Leneuve, Patricia
Géloën, Alain
Even, Patrick C.
Cervera, Pascale
Venue: Nature
Publisher: Springer Science and Business Media LLC
Published: 2002-12-04
Volume: 421
Issue: 6919
Pages: 182-187
ISSN: 0028-0836 (ISSN-L)
1476-4687
DOI: 10.1038/nature01298
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: green
hal.sorbonne-universite.fr
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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IGF-1 receptor regulates lifespan and resistance to oxidative stress in mice

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