NEW: Researchers at Yale and the University of California, San Francisco found that a single injection of the klotho protein led to modest improvements in cognitive function in older monkeys that lasted for two weeks. Could it one day help people?
They then administered a single low dose of klotho under each monkey’s skin, raising levels of the protein to those normally present in the animals at birth. Four hours later, researchers had them complete the food-finding task in batches of 20 trials, and the team then retested the monkeys over the next two weeks. Overall, the animals made correct choices more often than they did before receiving the injection.
People are born with about five times as much klotho as they have in adulthood—and in the monkey experiment, the low dose of klotho was equivalent to levels in infancy. Dubal speculates that dosing within a range that the body has experienced before, without overshooting, may be more important for primates than mice. The next step will be to test even lower doses in human clinical trials, to find the “therapeutic sweet spot for humans,” Dubal says.
But klotho is a big mystery: Nobody knows exactly how it acts on the brain. “That’s a complete black box,” says Verdin. Researchers think the protein must be protecting the brain in some way—but how? It doesn’t seem to cross the blood brain barrier, the semipermeable border of blood vessels and tissues that keeps many harmful substances away from the brain.
Given that the cognitive effect of klotho long outlasts its presence in the body, Dubal suspects it must have an effect on the connections between neurons in the brain, potentially “reengineering the synapse to better receive and keep memories,” she says. Her research group is currently working to understand how klotho gets into the brain, and what it does once it’s there.
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