Ageing is a complex biological process for which underlying biochemical changes are still largely unknown. We have found that the proteolytic enzyme caspase-2, contributes to ageing by regulating basal metabolism, proteostasis and oxidative stress [1]. Using Caspase-2 deficient (Casp2-/-) mice as a model of premature ageing in the absence of overt disease, we performed comparative “omics” profiling of to determine age-related changes t in the liver and serum of proteome and metabolome 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. Metabolic profile changes in young Casp2-/- resemble those found in aged wild-type miceIntriguingly, we found that aged Casp2-/- mice have reduced blood glucose and improved glucose tolerance compared to aged wild-types. Together, our results demonstrate a role for caspase-2 in proteome and metabolome remodelling during ageing. We have now expanded on these findings to further investigate the metabolic phenotype and altered metabolic homeostasis of Casp2-/- mice through nutritional deprivation and over-nutrition studies. Our results will be presented at this meeting.
[1] Wilson CH, Shalini S, Filipovska A, Richman TR, Davies S, Martin SD, McGee SL, Puccini J, Nikolic A, Dorstyn L, Kumar S. Age-related proteostasis and metabolic alterations in Caspase-2-deficient mice. Cell Death and Disease. 2015, 6: e1597