Brain benefits of exercise can be gained with a Liver protein

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According to a new study in mice by scientists in the UC San Francisco Eli and Edythe Broad Center for Regeneration Medicine and Stem Cell Research, a little-studied liver protein may be responsible for the well-known benefits of exercise on the aging brain, . The findings could lead to new therapies to confer the neuroprotective effects of physical activity on people who are unable to exercise due to physical limitations.

Exercise is one of the best-studied and most powerful ways of protecting the brain from age-related cognitive decline and has been shown to improve cognition in individuals at risk of neurodegenerative diseases such as Alzheimer’s disease and frontotemporal dementia—even those with rare gene variants that inevitably lead to dementia.

But many older adults are not able to exercise regularly due to physical limitations or disabilities, and researchers have long searched for therapies that could confer some of the same neurological benefits in people with low physical activity levels.

The new study, published July 9, 2020, in Science, showed that after mice exercise, their livers secrete a protein called Gpld1 into the blood. Levels of this protein in the blood correspond to improved cognitive function in aged mice, and a collaboration with the UCSF Memory and Aging Center found that the enzyme is also elevated in the blood of elderly humans who exercise regularly. But the researchers showed that simply increasing the amount of Gpld1 produced by the mouse liver could confer many of the same brain benefits as regular exercise.

“If there were a drug that produced the same brain benefits as exercise, everyone would be taking it. Now our study suggests that at least some of these benefits might one day be available in pill form,” said study senior author Saul Villeda, Ph.D., a UCSF assistant professor in the departments of Anatomy and of Physical Therapy and Rehabilitation Science.

Villeda’s lab has previously shown that biological factors present in the blood of young mice can rejuvenate the aging mouse brain, and conversely, factors in the blood of older mice can bring on premature age-related cognitive decline in young mice.