UCSF Study Finds Exercise Protein Strengthens Brain's Protective Barrier

Researchers uncover how an exercise-induced liver protein improves memory and slows age-related cognitive decline.

Published on Feb. 24, 2026

Got story updates? Submit your updates here. ›

Researchers at the University of California, San Francisco (UCSF) have discovered a mechanism that could explain how exercise improves cognition by strengthening the brain's protective blood-brain barrier. The study found that an exercise-induced liver protein called GPLD1 trims a harmful protein called TNAP from the cells that form the blood-brain barrier, making it less leaky and reducing brain inflammation associated with cognitive decline and conditions like Alzheimer's disease.

Why it matters

This discovery provides new insights into how the body's systems, particularly the liver, can impact brain health and function. By understanding this mechanism, researchers may be able to develop new therapeutic strategies to rejuvenate the blood-brain barrier and slow age-related cognitive decline, even in those who are unable to exercise.

The details

The researchers found that as mice age, cells in the blood-brain barrier accumulate more of the protein TNAP, which makes the barrier leaky. However, when mice exercise, their livers produce the protein GPLD1, which travels to the brain's blood vessels and trims off the TNAP from the barrier cells. Reducing TNAP levels helped improve memory and reduce brain inflammation in older mice. The team believes finding drugs to mimic this TNAP-trimming effect could be a new way to rejuvenate the blood-brain barrier even after it has been degraded by age.

  • Six years ago, the research team identified the brain-rejuvenating enzyme GPLD1 that mice produced in their livers when they exercised.
  • The new study, published in the journal Cell on February 18, 2026, answers how GPLD1 works to improve brain health.

The players

Saul Villeda

PhD, associate director of the UCSF Bakar Aging Research Institute and the senior author of the study.

Gregor Bieri

PhD, a postdoctoral scholar in Villeda's lab and co-first author of the study.

UCSF

The University of California, San Francisco, which is exclusively focused on the health sciences and dedicated to promoting health worldwide through advanced biomedical research, graduate-level education, and excellence in patient care.

Got photos? Submit your photos here. ›

What they’re saying

“This discovery shows just how relevant the body is for understanding how the brain declines with age.”

— Saul Villeda, PhD, associate director of the UCSF Bakar Aging Research Institute

“We were able to tap into this mechanism late in life, for the mice, and it still worked.”

— Gregor Bieri, PhD, postdoctoral scholar

What’s next

Researchers plan to further investigate whether drugs could be developed to mimic the TNAP-trimming effect of the GPLD1 protein, in order to rejuvenate the blood-brain barrier and slow age-related cognitive decline even in those unable to exercise.

The takeaway

This study uncovers a novel mechanism by which the body, specifically the liver, can impact brain health through the production of proteins that strengthen the blood-brain barrier. These findings open up new avenues for therapeutic strategies to address age-related cognitive decline beyond the traditional focus on the brain alone.