Selman, C;
Partridge, L;
Withers, DJ;
(2011)
Replication of Extended Lifespan Phenotype in Mice with Deletion of Insulin Receptor Substrate 1.
PLOS ONE
, 6
(1)
, Article e16144. 10.1371/journal.pone.0016144.
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Abstract
We previously reported that global deletion of insulin receptor substrate protein 1 (Irs1) extends lifespan and increases resistance to several age-related pathologies in female mice. However, no effect on lifespan was observed in male Irs1 null mice. We suggested at the time that the lack of any effect in males might have been due to a sample size issue. While such lifespan studies are essential to our understanding of the aging process, they are generally based on survival curves derived from single experiments, primarily due to time and economic constraints. Consequently, the robustness of such findings as a basis for further investigation has been questioned. We have therefore measured lifespan in a second, separate cohort of Irs1 null female mice, and show that, consistent with our previous finding, global deletion of Irs1 significantly extends lifespan in female mice. In addition, an augmented and completed study demonstrates lifespan extension in male Irs1 null mice. Therefore, we show that reduced IRS1-dependent signalling is a robust mechanism through which mammalian lifespan can be modulated.
| Type: | Article |
|---|---|
| Title: | Replication of Extended Lifespan Phenotype in Mice with Deletion of Insulin Receptor Substrate 1 |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1371/journal.pone.0016144 |
| Publisher version: | http://dx.doi.org/10.1371/journal.pone.0016144 |
| Language: | English |
| Additional information: | © 2011 Selman et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. This work was supported by Wellcome Trust (Functional Genomics and Strategic) awards to L.P. and D.J.W. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. |
| Keywords: | NUTRIENT HOMEOSTASIS, CALORIC RESTRICTION, HUMAN LONGEVITY, DWARF MICE, EXTENSION, RAPAMYCIN, PATHWAY |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Genetics, Evolution and Environment |
| URI: | https://discovery.ucl.ac.uk/id/eprint/1300256 |
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