The accelerated aging model reveals critical mechanisms of late-onset Parkinson\u2019s disease

Shiyan Li,Yin Wang,Hongxin Liu,Xianzheng Sha,Shiyu Bian,Yixue Li

doi:10.1186/s13040-020-00215-w

Abstract

BackgroundLate-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.ResultsIn 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.ConclusionsIn short, mechanisms between aging and LOPD were integrated by our computational pipeline.

Highlights

As the second most common neurodegenerative syndrome, Parkinson’s disease (PD, namely paralysis agitans), affects 1% of the worldwide population over the age of 60 years [1]
There were abundant epidemiological evidences supported that aging was the primary risk factor for Late-onset Parkinson’s disease (LOPD) [3]
The loss of substantia nigra (SN) neurons between normal aging and PD was significant, where the loss of neurons was 28.3% in older controls compared with younger controls, and the loss of pigmented neurons in PD was 73% compared with older controls [9]

Summary

Introduction

As the second most common neurodegenerative syndrome (only after Alzheimer’s disease), Parkinson’s disease (PD, namely paralysis agitans), affects 1% of the worldwide population over the age of 60 years [1]. It is characterized by the motor (i.e. resting tremor, movement slowness, rigidity, and postural instability) and nonmotor symptoms (i.e. hyposmia, sleep disorders, autonomic dysfunction, neuropsychiatric alterations, and sensory symptoms) [1]. 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.

Methods

Results

Conclusion