| | |  | | | | Record from Web of Science® | | | | | | |
| IGF-1 receptor regulates lifespan and resistance to oxidative stress in mice |
|
|
| Author(s): Holzenberger M, Dupont J, Ducos B, Leneuve P, Geloen A, Even PC, Cervera P, Le Bouc Y |
| Source: NATURE Volume: 421 Issue: 6919 Pages: 182-187 Published: JAN 9 2003 |
| Times Cited: 592 References: 30 |
| 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(1-3). 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. |
| Document Type: Article |
| Language: English |
| Reprint Address: Holzenberger, M (reprint author), INSERM, U515, F-75571 Paris 12, France |
Addresses:
1. INSERM, U515, F-75571 Paris 12, France
2. Hop St Antoine, Serv Anat & Cytol Pathol, F-75571 Paris, France
3. INRA, F-37380 Nouzilly, France
4. Inst Natl Sci Appl, INSERM, U352, F-69621 Villeurbanne, France
5. INA PG, INRA, F-75231 Paris 5, France |
| Publisher: NATURE PUBLISHING GROUP, MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND |
| Subject Category: Multidisciplinary Sciences |
| IDS Number: 633DR |
| ISSN: 0028-0836 |
| DOI: 10.1038/nature01298 |
|
| | | | | | | | | Record from Web of Science® | | | | | | | | | |