The Aging Substantia Nigra is Characterized by ROS Accumulation Potentially Resulting in Increased Neuroinflammation and Cytoskeletal Remodeling

Abstract

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