The accelerated aging model reveals critical mechanisms of late-onset Parkinson’s disease

Background Late-onset Parkinson’s disease (LOPD) is a common neurodegenerative disorder and lacks disease-modifying treatments, attracting major attentions as the aggravating trend of aging population. There were numerous evidences supported that accelerated aging was the primary risk factor for LOPD, thus pointed out that the mechanisms of PD should be revealed thoroughly based on aging acceleration. However, how PD was triggered by accelerated aging remained unclear and the systematic prediction model was needed to study the mechanisms of PD. Results In this paper, an improved PD predictor was presented by comparing with the normal aging process, and both aging and PD markers were identified herein using machine learning methods. Based on the aging scores, the aging acceleration network was constructed thereby, where the enrichment analysis shed light on key characteristics of LOPD. As a result, dysregulated energy metabolisms, the cell apoptosis, neuroinflammation and the ion imbalances were identified as crucial factors linking accelerated aging and PD coordinately, along with dysfunctions in the immune system. Conclusions In short, mechanisms between aging and LOPD were integrated by our computational pipeline.

Abstract licence: CC BY-NC-ND

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• Single-cell sequencing of human midbrain reveals glial activation and a Parkinson-specific neuronal state · 2021

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