Finding ways to stave off the cognitive decline that is common in old age could allow people to live healthy lives for longer. New research suggests injections of a specific protein could boost memory in older monkeys.
Diseases like Alzheimer’s can significantly degrade quality of life for older people even if they are otherwise physically healthy. As efforts to slow or reverse the signs of aging pick up their pace, it will be crucial to ensure that it’s not only peoples’ bodies that remain fighting fit.
Scientists have long suspected that a protein produced in the kidney called klotho could play an important role in aging, in particular for cognitive health. And now researchers have shown for the first time that low doses of the protein could significantly improve older monkeys’ ability to play a game that tests their memory, leading to hopes it could be used as an anti-aging therapy in people.
“Cognitive dysfunction in aging is a major biomedical challenge,” the authors wrote in a paper published in Nature Aging. “Systemic low-dose klotho treatment may prove therapeutic in aging humans.”
The protein is named after Klotho, one of the three Fates from Greek mythology who was said to spin the thread of life. It was discovered by accident in 1997 by researchers studying high blood pressure using genetically modified mice.
Some of their subjects exhibited shortened lifespans and a host of symptoms similar to those found in aging humans, such as clogged arteries, osteoporosis, and age-related skin changes. When the team investigated, they found the gene for klotho had been disrupted in these animals.
Subsequent studies demonstrated that the protein has multiple roles in the body, but its levels gradually decline as people age. And in 2014, the same researchers behind this new paper showed that older adults with higher levels of klotho performed better on cognitive tests.
This prompted the team to see if the protein could be administered therapeutically to boost brain function. In 2017, they showed that an injection of klotho could enhance cognition in both young and aging mice. The study suggested that the improvement could be down to the protein improving the function of synapses in the brain.
But mice are not very similar to people, so the researchers decided to test the approach in monkeys. They injected 18 macaques that were an average of 22 years old—equivalent to 65 in humans—with one of three doses of klotho. The first was designed to be roughly the same as the amount of klotho found in humans at birth, while the others were two and three times higher.
Four hours after administering the protein, the researchers subjected the macaques to a common memory test in which the animals have to remember where food has been hidden in an array of compartments. The monkeys were given two versions of the test, one of which was harder as it featured more compartments.
The team found that the monkeys’ performance on the easy test improved by about 6 percent compared to before the injection, but they did about 20 percent better on the hard one. The researchers continued to test the monkeys for the next two weeks and discovered that the cognitive boost persisted throughout this period.
“The fact that it can be given once and last for two weeks seems great, although we don’t know at this point whether repeated administration would work again,” Eric Verdin, CEO of the Buck Institute for Research on Aging, told Wired.
Exactly how the protein works is unclear, though. Klotho gets broken down by the body within a few days, so it can’t be its direct presence that’s causing the effect. It also doesn’t appear to be able to cross the blood-brain barrier, which protects the brain from harmful substances. Study leader Dena Dubal from the University of California, San Francisco, told Wired that her group is currently trying to work out the mechanism.
But getting the approach to work in primates, which are much more like humans than other model animals, is a significant achievement. “Given that most experiments in the aging 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,” João Pedro de Magalhães at the University of Birmingham, UK, told New Scientist.
Proving that the therapy could work in humans will take a lot more research, but a Bay Area company called Unity Biotechnology has licensed the rights to UCSF’s work. It is currently carrying out animal testing and has hopes of eventually conducting human trials of a klotho-based drug for cognitive disorders. That suggests it may not be too long before Klotho is spinning life’s thread just that little bit slower.