title: Age-related proteostasis and metabolic alterations in Caspase-2-deficient mice.
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.
authors.affiliation: Centre for Cancer Biology, University of South Australia, Adelaide, South Australia, Australia.
authors.forename: C H
authors.initials: CH
authors.lastname: Wilson
authors.affiliation: Centre for Cancer Biology, University of South Australia, Adelaide, South Australia, Australia.
authors.forename: S
authors.initials: S
authors.lastname: Shalini
authors.affiliation: 1] Mitochondrial Medicine and Biology Group, Harry Perkins Institute of Medical Research, Nedlands, Western Australia, Australia [2] School of Chemistry and Biochemistry, The University of Western Australia, Nedlands, Western Australia, Australia.
authors.forename: A
authors.initials: A
authors.lastname: Filipovska
authors.affiliation: Mitochondrial Medicine and Biology Group, Harry Perkins Institute of Medical Research, Nedlands, Western Australia, Australia.
authors.forename: T R
authors.initials: TR
authors.lastname: Richman
authors.affiliation: Mitochondrial Medicine and Biology Group, Harry Perkins Institute of Medical Research, Nedlands, Western Australia, Australia.
authors.forename: S
authors.initials: S
authors.lastname: Davies
authors.affiliation: 1] Metabolic Remodelling Laboratory, School of Medicine, Deakin University, Geelong, Victoria, Australia [2] Metabolism and Inflammation Program, Baker IDI Heart and Diabetes Institute, Melbourne, Victoria, Australia.
authors.forename: S D
authors.initials: SD
authors.lastname: Martin
authors.affiliation: 1] Metabolic Remodelling Laboratory, School of Medicine, Deakin University, Geelong, Victoria, Australia [2] Metabolism and Inflammation Program, Baker IDI Heart and Diabetes Institute, Melbourne, Victoria, Australia.
authors.forename: S L
authors.initials: SL
authors.lastname: McGee
authors.affiliation: Centre for Cancer Biology, University of South Australia, Adelaide, South Australia, Australia.
authors.forename: J
authors.initials: J
authors.lastname: Puccini
authors.affiliation: Centre for Cancer Biology, University of South Australia, Adelaide, South Australia, Australia.
authors.forename: A
authors.initials: A
authors.lastname: Nikolic
authors.affiliation: Centre for Cancer Biology, University of South Australia, Adelaide, South Australia, Australia.
authors.forename: L
authors.initials: L
authors.lastname: Dorstyn
authors.affiliation: Centre for Cancer Biology, University of South Australia, Adelaide, South Australia, Australia.
authors.forename: S
authors.initials: S
authors.lastname: Kumar
mesh_terms: D000375:Aging / Q000097:blood / Q000378:metabolism*; D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D053143:Caspase 2 / Q000172:deficiency* / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D018149:Glucose Intolerance; D006706:Homeostasis; D050356:Lipid Metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D055442:Metabolome; D055432:Metabolomics; D051379:Mice; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000378:metabolism; D009249:NADP / Q000378:metabolism; D010085:Oxidative Phosphorylation; D010427:Pentose Phosphate Pathway; D020543:Proteome / Q000378:metabolism*; D040901:Proteomics; D015203:Reproducibility of Results; D015398:Signal Transduction
chemical_list: D000596:Amino Acids; D020543:Proteome; D009249:NADP; C090208:Casp2 protein, mouse; D053143:Caspase 2; D005947:Glucose