In a new study, researchers found that a 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.
The research was conducted by scientists in the UC San Francisco.
Exercise is one of the best-studied and most powerful ways of protecting the brain from age-related cognitive decline.
It 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 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 the team 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.
The team says if there were a drug that produced the same brain benefits as exercise, everyone would be taking it.
This study suggests that at least some of these benefits might one day be available in pill form.
The team took blood from aged mice who had exercised regularly for seven weeks and administered it to sedentary aged mice.
They found that four weeks of this treatment produced dramatic improvements in learning and memory in the older mice, similar to what was seen in the mice who had exercised regularly. When they examined the animals’ brains, they found evidence of enhanced production of new neurons in the region known as the hippocampus, a well-documented proxy for the rejuvenating benefits of exercise.
To discover what specific biological factors in the blood might be behind these effects, the team measured the amounts of different soluble proteins in the blood of active versus sedentary mice.
They identified 30 candidate proteins, 19 of which, to their surprise, were predominantly derived from the liver and many of which had previously been linked to functions in controlling the body’s metabolism.
Two of these proteins—Gpld1 and Pon1—stood out as particularly important for metabolic processes, and the researchers chose to study Gpld1 in more detail because few previous studies had tested its function.
They found that Gpld1 increases in the blood circulation of mice following exercise, and that Gpld1 levels correlate closely with improvements in the animals’ cognitive performance.
Analysis of human data showed that Gpld1 is also elevated in the blood of healthy, active elderly adults compared to less active elders.
The lab is now hoping to find specific targets for therapeutics that could one day confer many of the protective benefits of exercise for the aging brain.
One author of the study is Saul Villeda, Ph.D., a UCSF assistant professor in the departments of Anatomy and of Physical Therapy and Rehabilitation Science.
The study is published in Science.
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