Aging, Parkinson's Disease, and Models: What Are the Challenges?

Area of Science:

• Neuroscience
• Gerontology
• Pathology

Background:

• Parkinson's disease (PD) is a neurodegenerative disorder with motor and non-motor symptoms, linked to dopaminergic neuron loss.
• PD incidence rises with age, suggesting aging mechanisms are involved in its development and progression.
• The specific role of aging in PD pathogenesis is understudied, and current preclinical models often neglect age as a factor.

Purpose of the Study:

• To highlight the understudied role of biological aging in Parkinson's disease pathogenesis.
• To identify limitations in current PD models regarding age-related factors.
• To advocate for systematic investigation into how aging affects PD susceptibility and progression in various models.

Main Methods:

• Review of existing PD models (cell, toxin-induced, genetic in rodents and nonhuman primates).
• Assessment of stem cell-derived patient neurons for aging features.
• Analysis of age-related changes in PD animal models.

Main Results:

• Current PD models often lack full characterization and time-course assessments, hindering conclusions about aging's role.
• Patient-derived neurons show some aging features, but characterization and reproducibility are suboptimal.
• Existing studies suggest an association between age-related changes and PD, but likely alongside other disease drivers.

Conclusions:

• A significant gap exists in understanding the role of biological aging in PD development and progression.
• Improved, age-inclusive preclinical models are needed for reliable investigation of PD.
• Coordinated research efforts and resource sharing are essential to advance PD research and model validation.