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Hormone injection may stem age-related memory decline

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Cognitive impairments such as memory loss are a common problem for older people

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A hormone that is claimed to regulate the ageing process enhances memory in monkeys, raising the prospect it could be used to prevent cognitive decline in people.

One injection of the compound, called klotho, improved results in memory tests for at least two weeks in older macaques. If the treatments give similar benefits in people, it would be a major breakthrough, says Dena Dubal at the University of California, San Francisco. “Cognitive dysfunction is one of our greatest biomedical challenges.”

Klotho was discovered when the gene for the hormone was disrupted accidentally in genetically altered mice. The mice then seemed to age faster.

Made by the kidneys, this hormone seems to have multiple roles in the body, including helping to control cell replication and development. Levels of klotho in the blood gradually fall in people as they get older, so the protein was named after Clotho, one of the Fates in Greek mythology, who was said to spin the thread of life.

Klotho has also been shown to improve memory in mice – perhaps by improving the brain’s ability to form new synapses, the connections between brain cells. To investigate whether it would have the same effect in primates, Dubal’s team tested three different doses in macaques that were an average of 22 years old, which is equivalent to about 65 years in people.

The animals were tested on their ability to remember where food had been hidden within an array of holes that were covered up. “This is similar to if you put your car keys down somewhere, then, a short time later, coming back and having to remember where they were,” says Dubal.

Within four hours of getting the klotho injection, the monkeys given the lowest dose did significantly better on the memory tests than those given a placebo shot. The effect lasted for at least two weeks, after which the testing stopped.

In a surprising result, however, those given higher doses didn’t do better than the placebo group. That may be because the low dose was designed to be equivalent to the levels seen in humans at birth, says Dubal. “It might be that klotho needs to be just replenished to a certain level rather than be given at huge pharmacologic doses.”

“Given that most experiments in the ageing field employ short-lived animal models – like mice, flies and worms – it is impressive that the authors performed these experiments in a non-human primate,” says João Pedro de Magalhães at the University of Birmingham, UK. But researchers need to find out why klotho wasn’t beneficial at higher doses, he says.

Charles Brenner at City of Hope in Duarte, California, says the inconsistent results and the fact that the researchers weren’t always “blinded” as to which monkeys received klotho and which had the placebo suggest the results may be untrustworthy.

“It does not bode well for producing reliable results,” he says. “I do not think that [the team] has established that klotho injections enhanced cognition in primates.”

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