Impact of aging on animal models of Parkinson´s disease

Ida Hyllen Klæstrup; Mie Kristine Just Pedersen; Karina Lassen Holm; Aage Kristian Olsen Alstrup; Marina Romero-Ramos; Per Borghammer; Nathalie Van Den Berge

doi:10.3389/fnagi.2022.909273

Impact of aging on animal models of Parkinson´s disease

Ida Hyllen Klæstrup, Mie Kristine Just Pedersen, Karina Lassen Holm, Aage Kristian Olsen Alstrup, Marina Romero-Ramos, Per Borghammer, Nathalie Van Den Berge

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

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Abstract

Aging is the biggest risk factor for developing Parkinson's disease (PD), the second most common neurodegenerative disorder. Several animal models have been developed to explore the pathophysiology underlying neurodegeneration and the initiation and spread of alpha-synuclein-related PD pathology, and to investigate biomarkers and therapeutic strategies. However, bench-to-bedside translation of preclinical findings remains suboptimal and successful disease-modifying treatments remain to be discovered. Despite aging being the main risk factor for developing idiopathic PD, most studies employ young animals in their experimental set-up, hereby ignoring age-related cellular and molecular mechanisms at play. Consequently, studies in young animals may not be an accurate reflection of human PD, limiting translational outcomes. Recently, it has been shown that aged animals in PD research demonstrate a higher susceptibility to developing pathology and neurodegeneration, and present with a more disseminated and accelerated disease course, compared to young animals. Here we review recent advances in the investigation of the role of aging in preclinical PD research, including challenges related to aged animal models that are limiting widespread use. Overall, current findings indicate that the use of aged animals may be required to account for age-related interactions in PD pathophysiology. Thus, although the use of older animals has disadvantages, a model that better represents clinical disease within the elderly would be more beneficial in the long run, as it will increase translational value and minimize the risk of therapies failing during clinical studies. Furthermore, we provide recommendations to manage the challenges related to aged animal models.

Original language	English
Article number	909273
Journal	Frontiers in Aging Neuroscience
Volume	14
Number of pages	21
ISSN	1663-4365
DOIs	https://doi.org/10.3389/fnagi.2022.909273
Publication status	Published - 28 Jul 2022

Keywords

Alpha-synuclein (a-Synuclein)
Parkinson's disease
aging
animal models
autonomic nervous system
gut-brain axis

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abstract = "Aging is the biggest risk factor for developing Parkinson's disease (PD), the second most common neurodegenerative disorder. Several animal models have been developed to explore the pathophysiology underlying neurodegeneration and the initiation and spread of alpha-synuclein-related PD pathology, and to investigate biomarkers and therapeutic strategies. However, bench-to-bedside translation of preclinical findings remains suboptimal and successful disease-modifying treatments remain to be discovered. Despite aging being the main risk factor for developing idiopathic PD, most studies employ young animals in their experimental set-up, hereby ignoring age-related cellular and molecular mechanisms at play. Consequently, studies in young animals may not be an accurate reflection of human PD, limiting translational outcomes. Recently, it has been shown that aged animals in PD research demonstrate a higher susceptibility to developing pathology and neurodegeneration, and present with a more disseminated and accelerated disease course, compared to young animals. Here we review recent advances in the investigation of the role of aging in preclinical PD research, including challenges related to aged animal models that are limiting widespread use. Overall, current findings indicate that the use of aged animals may be required to account for age-related interactions in PD pathophysiology. Thus, although the use of older animals has disadvantages, a model that better represents clinical disease within the elderly would be more beneficial in the long run, as it will increase translational value and minimize the risk of therapies failing during clinical studies. Furthermore, we provide recommendations to manage the challenges related to aged animal models.",

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AU - Pedersen, Mie Kristine Just

AU - Holm, Karina Lassen

AU - Alstrup, Aage Kristian Olsen

AU - Romero-Ramos, Marina

AU - Borghammer, Per

AU - Van Den Berge, Nathalie

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Impact of aging on animal models of Parkinson´s disease

Abstract

Keywords

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