Investigating the Mitochondrial Basis of Neuronal ageing

与年龄相关的认知能力下降的确切细胞生物学机制尚不清楚。脑老化是由累积的损伤引起的，损伤会导致神经元功能障碍、组织衰竭，最终导致死亡。已经提出了许多衰老理论，这些理论都集中在能量产生细胞器线粒体的逐渐损伤上。线粒体功能是如何随着年龄的增长而下降的，这个问题一直存在争议。年龄与氧化功能下降、线粒体DNA突变积累、动力学（裂变/融合/运输）下降、脂质成分变化和活性氧（ROS）积累有关。目前我们还不知道哪种与年龄相关的线粒体变化是其他线粒体扰动的驱动力，也不知道哪种与年龄相关的线粒体变化是导致大脑衰老的主要原因。我们之前的研究表明，线粒体动力学会随着年龄的增长而发生显著改变（Smith等人，2019 Neuron & Lin T-H等人，2021 PNAS），该项目将研究这一过程背后的机制

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