NIH Transformative Research Award: ‘A New Muscle-Brain Axis Underlying the Cognitive Benefits of Physical Activity’

Dr. Rando and his co-principal investigator, Tony Wyss-Coray, PhD, were awarded one of 10 Transformative Research by the NIH. These awards, open to both individuals and teams of investigators, were created to support research projects that have the potential to create or overturn fundamental paradigms.

“Thomas Rando, MD, PhD, professor of neurology, and Tony Wyss-Coray, PhD, professor of neurology and a senior research career scientist at the Veterans Affairs Palo Alto Health Care System, have received a $4.26 million award to explore the basis for physical activity’s robust positive effect on cognitive function.

Aging is associated with a progressive decline in cognitive ability, the consequences of which can be enormous for individuals and society. Muscle is increasingly understood to be a secretory tissue with effects on bone structure, metabolism and blood vessel formation.

Using innovative experimental models and tools, the Rando and Wyss-Coray teams will test the idea that factors produced in exercised muscle are secreted into the circulation, where they gain access to the brain and induce cognitive benefits. In particular, the researchers will investigate the mechanisms by which the profile of factors secreted by muscle tissue changes during exercise.

Further, they will identify the neural cells whose behavior is modified by those secreted factors and that mediate the effects those factors induce during exercise, as well as afterward. The results of these endeavors may drastically alter current thinking about exercise’s beneficial effects on the brain cells’ function and regeneration, remodeling of neuronal circuitry, and cognition itself.

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