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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
Editor: Raschellà, G.
Statement of
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
Mice, Inbred C57BL
Glucose Intolerance
Amino Acids
Reproducibility of Results
Signal Transduction
Oxidative Phosphorylation
Pentose Phosphate Pathway
Lipid Metabolism
Caspase 2
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
DOI: 10.1038/cddis.2014.567
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