Investigating the Mitochondrial Basis of Neuronal ageing

The exact cellular biological mechanisms of age related cognitive decline are poorly understood. Brain ageing is caused by accumulated damage that leads to neuronal dysfunction, tissue failure, and ultimately death. A number of ageing theories have been proposed which have been centred around the gradual damage of the energy generating organelle the mitochondria. How mitochondrial function declines with age has been long debated. Age has been associated with decreased oxidative function, accumulation of mitochondrial DNA mutations, decreased dynamics (fission/ fusion/transport), lipid compositions changes and build-up of reactive oxygen species (ROS). Currently we don't know which agerelated mitochondrial change is the driving force for other mitochondrial perturbations and exactly what age related mitochondrial change is the major contributor to the ageing brain. Our work has previously shown that mitochondrial dynamics are significantly altered by age (Smith et al., 2019 Neuron & Lin T-H et al., 2021 PNAS) and this project will investigate mechanisms behind this processes