Aging is Often Overlooked in Mouse Models of Age-Related Conditions
Academic research is, as a rule, always short of funding. Researchers are consistently strongly motivated to find less costly approaches to animal studies. One aspect of this pressure is that the standard, most widely used animal models of disease tend to be the ones that can be created as rapidly as possible, using various toxic, damaging strategies to reproduce aspects of aging in relatively young mice. Time has its own cost, and budgets don't stretch to waiting around for mice to get old. Thus in this modern era of enthusiasm for targeting the mechanisms of aging, the research community finds itself in the position of knowing too little about how aging interacts with disease processes.
Mouse models of Parkinson's disease (PD) are invaluable for advancing our understanding of the disease, and there is much hope that their use will help develop new therapeutic interventions. PD is a complex multisystem disorder characterized by a spectrum of motor and non-motor symptoms, and numerous mouse models have been developed to study its various aspects. While age is the primary risk factor for PD, the role of biological aging in PD is still unclear, and it is often overlooked in the design and application of these models. This omission risks missing critical insights into disease mechanisms and opportunities for the development and translation of novel interventions, in particular as aging biology is emerging as a therapeutic target.
The International Network for Parkinson's Disease Modelling and AGEing (PD-AGE), funded by the Michael J. Fox Foundation for Parkinson's Research, was established to address critical gaps in our understanding of the role of aging in PD. Its creation was prompted by a workshop that brought together leading experts in PD modeling and aging who collectively highlighted the need for a systematic investigation into how aging contributes to PD.
To achieve its goals, PD-AGE was divided into four working groups, each focusing on different models. Here, we report on the working group that focused on approaches using mouse models and conducted a series of workshops to build consensus on prioritizing models of aging and PD, experimental approaches, and the standardization of protocols for their characterization. The result is a comprehensive roadmap for selecting optimal models, defining relevant measurements, and harmonizing protocols.