The aging Substantia nigra is characterized by ROS accumulation potentially resulting in a perturbed mitochondrial homeostasis, increased neuroinflammation and cytoskeletal remodelling

Ageing is a progressive and irreversible process that ultimately leads to death, serving as the primary risk factor for neurodegenerative disorders. This study aims to identify the molecular mechanisms underlying physiological ageing within the substantia nigra, which is primarily affected in Parkinson's disease and to draw potential conclusions on the earliest events leading to neurodegeneration in this specific brain region. The characterisation of essential stages in ageing progress could enhance knowledge of the mechanisms that promote the development of Parkinson's disease. To gain a comprehensive overview we utilized three study groups young individuals with a mean age of 28.7, middle-aged with a mean age of 62.3 and elderly individuals (mean age: 83.9). Using our proteomic approach, we were able to identify crucial features of physiological aging. These include heightened oxidative stress, enhanced lysosomal degradation, autophagy, remodelling of the cytoskeleton, changes in the structure of the mitochondria, alterations in vesicle transportation, and synaptic plasticity.