Impact of aging on animal models of Parkinson´s disease

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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 languageEnglish
Article number909273
JournalFrontiers in Aging Neuroscience
Pages (from-to)1-21
Publication statusPublished - 28 Aug 2022

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