Aging appears to alter how key cerebellar neurons fire, with measurable effects on movement and coordination.
Aging often brings slower movement, weaker balance, and reduced agility, but the brain changes behind these losses have been difficult to identify. McGill University researchers have now directly linked declining activity in Purkinje cells, an important type of neuron in the cerebellum, to measurable deterioration in gait, balance, coordination, and physical function.
“By demonstrating how the changes that happen to Purkinje cells in age are causally linked to changes in gait, motor coordination and balance, our work provides new avenues for therapies that may prevent or delay motor aging,” explained Eviatar Fields, the study’s lead author and McGill doctoral student in the Integrated Program in Neuroscience. “This provides new hope for extending health span and ultimately improving quality of life and independence in elderly people.”
The results could inform public health efforts aimed at preventing falls. They may also help researchers understand why comparable disruptions in brain activity appear in Alzheimer’s disease and other neurodegenerative conditions.
The research was conducted with Professor Alanna Watt’s lab in the Department of Biology.
Aging slows movement control cells
Purkinje cells combine sensory information with signals from within the body, then send corrections that help movements remain accurate. Unlike many other neurons, they also generate electrical signals spontaneously. To examine how this activity changes with age, the researchers tested motor coordination in mice ranging from young adults (two months old) to elderly animals (18 to 24 months old). Older mice performed more poorly on several tasks, including walking across an elevated beam and remaining on a rotating rod (Rotarod), reflecting movement declines also seen in aging humans.
Recordings from Purkinje cells showed that the neurons fired much less frequently in older mice. To determine whether that reduction was responsible for the poorer performance, the researchers used a genetically targeted tool called a DREADD, a designer receptor that can raise or lower a neuron’s excitability when activated.
Changing neuron activity changes performance
“When we turned on the DREADD for young mice, which made their Purkinje cells fire at lower rates, mimicking the older Purkinje cells, we found that they jumped off the Rotarod sooner than young mice who did not have the DREADD,” Fields explained. The reverse was also true: when the researchers increased neuron firing in older mice, the animals remained on the Rotarod longer, indicating better motor coordination.
“We showed that spontaneous firing rates in older Purkinje cells are reduced, and if we reverse this, we improve coordination. This indicates that the change plays a direct role in the age-related decline of motor coordination,” Fields said.
A separate task produced the same overall pattern. After learning to pull a one-meter string to receive a cereal reward, older mice made more errors than younger animals. Increasing Purkinje cell activity in the older mice significantly reduced the number of mistakes they made.
Professor Watt, study co-author, said continued research on motor coordination is important as populations age.
“Motor coordination has been under-explored in the aging field. It’s important to study this, because as coordination declines, falls become more common, which can have a catastrophic impact on quality of life,” she said.
Reference: “Cerebellar Purkinje cell firing reduction contributes to aging-related declining motor coordination in mice” by Eviatar Fields, Ben C. Rogers, Tsz Chui Sophia Leung, Andy Huang, Megan Kern, Nell Kontowicz, Hannah Dolin and Alanna J. Watt, 2 January 2026, Proceedings of the National Academy of Sciences.
DOI: 10.1073/pnas.2525795122
The research was funded by the Canadian Institutes for Health Research, the Canada First Research Excellence Fund, the Fonds de recherche du Québec, the Natural Sciences and Engineering Research Council of Canada and a Dr. Stephen J. Zalcman Memorial Scholarship.
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