At the University of Rhode Island College of Pharmacy and the George and Anne Ryan Institute for Neuroscience, Associate Professor Jaime Ross and Research Assistant Professor Giuseppe Coppotelli are investigating two of the most pressing questions in brain health today: how cellular energy systems influence aging and how environmental toxins may accelerate neurodegenerative disease.
Their research focuses on mitochondria, the energy-producing structures inside cells that play a critical role in metabolism, inflammation and cellular survival. When mitochondria malfunction, the effects can ripple throughout the body. Mitochondrial dysfunction has been linked to a range of diseases, including diabetes, cardiovascular disease, cancer and neurodegenerative disorders such as Alzheimer’s disease.
Ross and Coppotelli are studying how mutations in mitochondrial DNA contribute to aging and age-related diseases. Supported by a five-year, $2.8 million grant from the National Institute on Aging, their research uses innovative mouse models that carry mitochondrial mutations known to trigger premature aging.
In these models, mice begin to display aging symptoms early in life, including gray hair, hair loss and reduced mobility. The model provides researchers with a powerful tool for studying how mitochondrial dysfunction develops and how it affects tissues throughout the body.
One of the team’s most striking discoveries involves the effects of exercise. When the genetically modified mice were given access to voluntary exercise through a running wheel, the results were dramatic. Exercising mice maintained healthy fur, moved more quickly and appeared significantly younger than sedentary animals with the same mitochondrial mutations.
“Exercise is the only intervention that can dramatically improve the phenotype in these mice so that you cannot distinguish a mouse that has this mutation from a normal animal.”Giuseppe Coppotelli, Ph.D.
Although exercise did not correct the underlying genetic mutation, it significantly improved health during the animals’ lifespan. These findings suggest that physical activity may help cells identify and remove damaged mitochondria while promoting the production of new, healthy ones.
The team is now expanding this work using new models that allow them to study mitochondrial dysfunction in specific tissues such as the brain, heart and muscle. This approach may help identify targeted interventions that improve cellular energy metabolism and delay the onset of age-related disease.
Alongside this work on aging, Ross is also investigating how environmental exposures influence brain health. In a recent study published in Environmental Research Communications, her team examined how micro- and nanoplastics affect cognitive function in mice.
Microplastics are increasingly present in food, water and air, and previous studies from Ross’ lab have shown that these particles can cross the blood-brain barrier and accumulate in brain tissue.
To explore how this exposure may affect neurological health, the researchers studied mice carrying the APOE4 gene variant, a genetic risk factor that significantly increases the likelihood of developing Alzheimer’s disease.
After exposure to microplastics in drinking water, the mice exhibited measurable behavioral changes. Male mice displayed altered exploratory behavior linked to apathy, while female mice showed impaired memory when tested on their ability to recognize new objects.
These sex-dependent behavioral changes closely mirror patterns observed in human Alzheimer’s patients, where men often show greater apathy while women tend to experience more pronounced memory decline.
These findings suggest that environmental toxins such as microplastics may interact with genetic risk factors to accelerate neurological changes associated with Alzheimer’s disease.
Ross continues to expand this research while advocating for increased study of the human health impacts of microplastic exposure. Indeed, Ross was invited to participate in a historic joint hearing between U.S. Environmental Protection Agency (EPA) Administrator Lee Zeldin and U.S. Department of Health and Human Services (HHS) Secretary Robert F. Kennedy Jr. announcing coordinated actions to address microplastics contamination, one of the most urgent and growing public health challenges facing Americans.
Together, the work of Ross and Coppotelli highlights how both internal biological processes and external environmental factors influence aging and brain health. By uncovering the mechanisms that link cellular energy metabolism, lifestyle factors and environmental exposures, their research aims to identify new strategies to protect the brain and improve health across the lifespan.
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