Researchers at the University of California, San Francisco, have found that administering a fragment of the klotho – a life-extending protein hormone that a minority of people naturally produce at high levels – to young, aging or impaired mice rapidly improves their cognitive and physical performance.

While previous studies had revealed associations between elevated klotho levels and better cognition, that research had been done with mice genetically engineered to continuously produce high klotho levels and in people carrying genetic variants that caused them to have high klotho levels throughout life.

As a result, it was unclear whether klotho could be administered like a drug to rapidly enhance cognitive functioning in mice or people with normal or low levels of the hormone.

Published online recently in Cell Reports, the new study by Dena Dubal, associate professor of neurology and senior author of the paper, and her colleagues found clear evidence of improved cognition across a range of domains, including spatial learning and memory, as well as working memory.

The beneficial effects that the team saw in young mice occurred within hours, and they far outlasted the time that klotho remained active in the body, suggesting that there is a long-lasting effect of even a single treatment. And in testing aged mice that, at 18 months old, are at about the same stage in the mouse lifespan as a 65-year-old human, the team found that a single injection of klotho was enough to significantly improve their ability to navigate and to learn new tasks.

In addition, the researchers looked at mice that were engineered to produce a human protein called alpha-synuclein, which is a hallmark of Parkinson's disease and contributes to Alzheimer's disease. Giving klotho to these mice improved their motor function. The klotho-treated mice also learned better and were more willing than untreated mice to explore new territory, even though their brains remained loaded with toxic proteins.

Naturally produced in both the kidney and the brain, klotho is a complex hormone that affects many different systems in the body. Once produced, it lodges itself in cell membranes, then enzymes cleave off a portion that circulates in the blood and the cerebrospinal fluid that bathes the brain and spinal cord.

The new findings about klotho, according to Dubal in a news release from UCSF, are helping to illuminate the dimly understood connections between the body and the brain.

(Top photo credit to VCG Photo.)