Even though aging is the largest risk factor for Parkinson's disease, the majority of research aimed at taming the incurable neurodegenerative motor disease has largely left aging out of the mix. A group of researchers from around the globe seek to change that. "Unraveling the intersection of aging and Parkinson's disease: a collaborative road map for advancing research models," is now available online at the Nature publication npj Parkinson's Disease.
The vast majority of the Parkinson's research done in the lab of Buck professor Juie Andersen, PhD does involve looking at the disease through the lens of aging. Andersen is one of the senior authors of the paper. "Many age-related changes in the brain mirror those seen in the early stages of Parkinson's," she said, noting that many of the whole-body hallmarks of aging, including mitochondrial dysfunction, impaired autophagy, increased inflammation and cellular senescence have been shown to contribute to the disease. "The research community needs to approach this disease holistically and aging is the place to start. Aging biology is emerging as a therapeutic target." Minna Schmidt, PhD, a postdoctoral fellow in the Andersen lab was first author of the paper.
An estimated 1 million Americans have Parkinson's; globally the estimate exceeds 10 million, with numbers on the rise as aging populations increase in developed countries. Researchers make the case for the focus on aging by pointing out that only 10 percent of cases are based on family history. Most Parkinson's is sporadic, arising spontaneously from a mix of factors including age, genetic vulnerability, environmental exposures and poor lifestyle choices. "When we reviewed studies that include aging we concluded that the influence of aging on Parkinson's is subtle, emerges gradually and likely interacts synergistically with other contributing factors," says Andersen.
Andersen and her colleagues came up with a comprehensive roadmap that identifies mouse models that are best utilized for preclinical experiments that incorporate aging as a central element of Parkinson's disease pathogenesis. The roadmap also aims to standardize methodologies, foster cooperation and optimize resource utilization. "As a group we recognize that the complexity and diversity of Parkinson's models, combined with the lengthy nature of aging studies, present challenges that require substantial resources and innovative approaches," says Andersen. "Our work is aimed at making it easier for researchers to include aging as a critical element of their efforts to tackle this disease."
This paper is part of a larger effort from a 4-year consortium funded by the Michael J. Fox Foundation. In addition to this work which involves guidelines for mouse models, other papers focus on the use of human cell cultures and primates in Parkinson's research.
CITATION: Unraveling the intersection of aging and Parkinson's disease: a collaborative roadmap for advancing research models
DOI: 10.1038/s41531-025-01239-x
Additional Coauthors include: AM Cuervo, Institute for Aging Research, Albert Einstein College of Medicine, Bronx, NY; KL Double, Brain and Mind Centre and School of Medical Sciences, The University of Sydney, Sydney, Australia; D Ehniger, German Center for Neurodegenerative Diseases, Venusberg-Campus, Bonn Germany; MS Goldberg, Center for Neurodegeneration and Experimental Therapeutics, University of Alabama at Birmingham, Birmingham, AL; K Harvey, School of Pharmacy, University College London, UK; JHJ Hoeijmakers and PG Mastroberadino, Department of Molecular Genetics, Erasmus MC Cancer Institute, Erasmus University Medical Center, Rotterdam, The Netherlands ; KC Luk, Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA; DJ Moore, Department of Neurodegenerative Science, Van Andel Institute, Grand Rapids, MI; LJ Niedernhofer, Institute on the Biology of Aging and Metabolism, Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, MN; LE Trudeau, Department of Pharmacology and Physiology, Department of Neurosciences, Faculty of Medicine, Université de Montréal, Montréal, Canada; D Jurk, Mayo Clinic, Department of Physiology and Biomedical Engineering, Robert and Arlene Kogod Center on Aging, Rochester, MN ; I Bellantuono, School of Medicine and Population Health, Healthy Lifespan Institute, University of Sheffield, UK
Acknowledgments: This work was funded by the Michael J. Fox Foundation (MJFF-022769) and NIH/NIA AG062413
About the Buck Institute for Research on Aging
At the Buck, we aim to end the threat of age-related diseases for this and future generations. We bring together the most capable and passionate scientists from a broad range of disciplines to study mechanisms of aging and to identify therapeutics that slow down aging. Our goal is to increase human health span, or the healthy years of life. Located just north of San Francisco, we are globally recognized as the pioneer and leader in efforts to target aging, the number one risk factor for serious diseases including Alzheimer's, Parkinson's, cancer, macular degeneration, heart disease, and diabetes. The Buck wants to help people live better longer. Our success will ultimately change healthcare. Learn more at: https://buckinstitute.org
