martin-agerelated-2015.pdf (1.84 MB)
Age-related proteostasis and metabolic alterations in Caspase-2-deficient mice.
journal contribution
posted on 2015-01-01, 00:00 authored by C H Wilson, S Shalini, A Filipovska, T R Richman, S Davies, Sheree MartinSheree Martin, Sean McgeeSean Mcgee, J Puccini, A Nikolic, L Dorstyn, S KumarAgeing 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.
History
Journal
Cell Death and DiseaseVolume
6Pagination
e1597 - e1597Publisher
Nature Publishing GroupLocation
EnglandPublisher DOI
eISSN
2041-4889Language
engPublication classification
C Journal article; C1 Refereed article in a scholarly journalCopyright notice
2015, Nature Publishing GroupUsage metrics
Categories
No categories selectedKeywords
Licence
Exports
RefWorks
BibTeX
Ref. manager
Endnote
DataCite
NLM
DC