Each monkey was then given a single low dose of Klotho under the skin to raise the protein levels to those normally present in animals at birth. After four hours, the researchers divided the monkeys into 20 trials to complete a food-finding task, after which the team retested them over the next two weeks. Overall, the animals made more correct choices than before they received the injection. The research team tested monkeys with two versions of the task. An easy version with fewer compartments to choose from, and a more difficult version with more compartments to choose from. According to Duvall, Kroto improved performance on easy tasks by about 6 percent and on harder tasks by about 20 percent.
“This is very encouraging,” says Mo, who was not involved in the new study.
The researchers let the monkeys do this task several times over a two-week period, and found that even though klotho was broken down in the body within a few days after injection, the cognitive-enhancing effects persisted throughout. “The fact that a single dose lasts for two weeks sounds great, but we don’t know at this time if repeated doses will work again,” said Eric, CEO of the Buck Aging Institute.・Bardin says: He is not involved in research.
Indeed, previous studies using mice, both low and high doses of klotho enhanced cognition and helped perform better in some maze tasks that challenge learning and memory. But when Duvall’s team gave monkeys doses of 10, 20, and 30 micrograms per kilogram of body weight, the effect plateaued at the 10 microgram dose. This sets an important flag for researchers, as they are considering testing Klotho injections on humans one day. As for dosage, “more isn’t always better,” says Verdin.
People are born with about 5 times more klotho than in adulthood. And in monkey experiments, low doses of Klotho were comparable to infant levels. Duvall speculates that it may be more important for primates than for mice to dose within the range the body has previously experienced and without overshooting. The next step will be testing even lower doses in human clinical trials to find a “therapeutic sweet spot for humans,” Duvall said. “Brain health may require supplementation rather than overdose.”
But klotho is a big mystery. No one knows exactly how klotho works on the brain. “It’s a complete black box,” Verdin says. Researchers believe that this protein must protect the brain in some way, but how? It appears to be unable to cross the blood-brain barrier, a semi-permeable boundary.
Given that klotho’s cognitive effects last longer than it exists in the body, it is likely that klotho affects the connections between neurons in the brain, potentially “regenerating synapses to better receive and retain memories.” Duvall speculates that it might be possible to “design it.” Her research group is now working to understand how Klotho gets into the brain and what it does once it gets there.
