Please use this identifier to cite or link to this item:
https://hdl.handle.net/2440/94376
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Type: | Journal article |
Title: | Age-related proteostasis and metabolic alterations in Caspase-2-deficient mice |
Author: | Wilson, C. Shalini, S. Filipovska, A. Richman, T. Davies, S. Martin, S. McGee, S. Puccini, J. Nikolic, A. Dorstyn, L. Kumar, S. |
Citation: | Cell Death and Disease, 2015; 6(1):e1597-1-e1597-12 |
Publisher: | Nature |
Issue Date: | 2015 |
ISSN: | 2041-4889 2041-4889 |
Editor: | Raschellà, G. |
Statement of Responsibility: | CH Wilson, S Shalini, A Filipovska, TR Richman, S Davies, SD Martin, SL McGee, J Puccini, A Nikolic, L Dorstyn, and S Kumar |
Abstract: | Ageing is a complex biological process for which underlying biochemical changes are still largely unknown. We performed comparative profiling of the cellular proteome and metabolome to understand the molecular basis of ageing in Caspase-2-deficient (Casp2−/−) mice that are a model of premature ageing in the absence of overt disease. Age-related changes were determined in the liver and serum of young (6–9 week) and aged (18–24 month) wild-type and Casp2−/− mice. We identified perturbed metabolic pathways, decreased levels of ribosomal and respiratory complex proteins and altered mitochondrial function that contribute to premature ageing in the Casp2−/− mice. We show that the metabolic profile changes in the young Casp2−/− mice resemble those found in aged wild-type mice. Intriguingly, aged Casp2−/− mice were found to have reduced blood glucose and improved glucose tolerance. These results demonstrate an important role for caspase-2 in regulating proteome and metabolome remodelling during ageing. |
Keywords: | Liver Mitochondria Animals Mice, Inbred C57BL Mice Glucose Intolerance NADP Glucose Amino Acids Proteome Reproducibility of Results Proteomics Signal Transduction Oxidative Phosphorylation Aging Homeostasis Male Pentose Phosphate Pathway Lipid Metabolism Caspase 2 Metabolomics Metabolome |
Rights: | Cell Death and Disease is an open-access journal published by Nature Publishing Group. This work is licensed under a Creative Commons Attribution 4.0 International Licence. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons licence, users will need to obtain permission from the licence holder to reproduce the material. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0 |
DOI: | 10.1038/cddis.2014.567 |
Grant ID: | http://purl.org/au-research/grants/nhmrc/1073771 |
Published version: | http://dx.doi.org/10.1038/cddis.2014.567 |
Appears in Collections: | Aurora harvest 7 Medicine publications |
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hdl_94376.pdf | Published version | 1.88 MB | Adobe PDF | View/Open |
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