Mitochondrial ageing in rat brain areas and human fibroblasts

Understanding molecular processes underlying ageing still remains a challenge. Besides genetic determinants and the detrimental effects of reactive oxygen species (ROS), age-dependent changes in the abundance and post-translational modification of the cellular proteome are currently considered as targets and even triggers of ageing. At the protein level, numerous alterations in both the abundance and specific post-translational modification have been previously observed for a variety of established ageing models that might represent control determinants of evolutionary conserved life- and health-span. In this doctoral thesis, the mitochondrial proteome and its alterations during ageing were studied, with a focus specifically on the oxidative phosphorylation machinery. Data obtained from protein profiling of rat brain cortex, striatum and hippocampus of two different age states were compared to that of human fibroblasts undergoing senescence and/or irradiated fibroblasts exposed to X-rays or heavy ions. The focus was on the quantitative analysis of individual Oxidative Phosphorylation (OxPhos) complexes, respiratory chain supercomplexes and ATP synthase oligomers, as well as other non-OxPhos proteins that might be involved in the process of ageing, senescence or radiation response. The most important goal was to determine the overall mechanisms (in vivo and in vitro) in the largely unknown fundamental molecular processes involved in both ageing and senescence.