This May Explain How Exercise Protects Aging Brains

Mouse study links liver protein from exercise to stronger blood-brain barrier
Posted Mar 24, 2026 8:01 AM CDT
This May Explain How Exercise Protects Aging Brains
Scientists say the protein GPLD1 could potentially be used to improve the blood-brain barrier of people who are unable to exercise.   (Getty Images/Makhbubakhon Ismatova)

Scientists have found a potential clue to how exercise staves off cognitive decline: A new study in Cell reports that in mice, exercise prompts the liver to release a protein that appears to shore up the brain's protective borders and sharpen thinking—even in animals bred to develop an Alzheimer's-like condition. The protein, called GPLD1, doesn't enter the brain itself. Instead, it seems to act on the blood-brain barrier, a cellular lining that keeps harmful substances out but tends to weaken with age, per the Washington Post. Most intriguingly, the researchers found that older, inactive mice engineered to produce extra GPLD1 performed better on memory tests and grew more new neurons, similar to animals that had actually exercised.

The study suggests GPLD1 can reduce brain plaques linked to Alzheimer's by up to 30% in mice, per PNAS' Journal Club. The team traced the effect to GPLD1 trimming back a protein called TNAP, which accumulates on blood-brain barrier cells with age and makes the barrier leakier. Raised levels of TNAP have been found in the blood-brain barriers of older, sedentary people, while higher GPLD1 levels have been found in older people who reported regular walking, just as in exercising mice. Experts caution that the work in mice may not translate cleanly to humans, but say it advances understanding of how movement defends the brain. The researchers now hope to test their theory on humans, and even to test GPLD1-based "artificial exercise" for people who can't be active.

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