A team of health care specialists and neuroscientists affiliated with several institutions in the US has discovered that a single subcutaneous injection of a protein called klotho into elderly rhesus macaques was enough to lead to significant improvements in the memory of work and their ability to perform certain tasks. This result confirms previous studies with mice and opens the possibility that this “fountain of youth” protein may also work in humans.
In their article, published in the journal Nature Aging, the team of researchers from Yale University’s Medidina School and UCLA describe experiments they conducted giving aged monkeys the rhesus form of klotho. Previous research suggested that klotho, which is naturally produced in the kidneys and circulates in the blood, has an impact on both lifespan and overall health, hence why it has been renamed the longevity protein in some media.
It was first discovered in 1997 by pathologist Makoto Kuro-o at the National Institute of Neuroscience in Tokyo. His team of researchers found that mice lacking normal amounts of klotho tended to suffer effects similar to aging. They also found that older mice with higher levels of klotho in their blood tended to live longer. Previous research has shown that human klotho levels tend to decline in most people as they age.
And that is why, in recent years, this klotho protein has grabbed many headlines and research efforts on aging. It is an endogenous protein found in the cell membrane of various organs, but it is also released into the blood in the form of a hormone. Among other things, it influences insulin balance, the signaling chains of certain growth factors, and various receptor functions. Newborns and young children produce it in abundance, but then its levels gradually decline throughout life.
What is surprising is that although this protein hormone cannot cross the blood-brain barrier, it also appears to affect the brain and mental performance: “Studies show that people with genetically elevated levels of Klotho improve their mental performance as they age, and show delayed neuropathological symptoms and a reduced risk of senile dementia and Alzheimer’s disease,” explains Stacy Castner of Yale University.
They restore the levels of klotho to the usual amounts in a baby
In this new effort, the research team wanted to find out whether giving the protein to aging monkeys would slow or restore cognitive function. To do this, they selected 18 rhesus macaques that were equivalent in age to humans who were 65 years or older. Each was tasked with making their way through a maze to find a hidden gift. They were then encouraged to repeat the maze to see how well they remembered the most direct path to the treat. Subsequently, the researchers injected each of the monkeys with klotho; the amount raised their levels to what they were when they were babies.
After four hours, the monkeys performed the test again with different mazes. They repeated the tests several times over the next two weeks. Looking at their results, the team found that giving the monkeys klotho led to improvements in working memory. They also found that the monkeys saw more improvements when the paths of the maze were more difficult to remember, in some cases by as much as 20%.
The researchers also found that the effects of giving the monkeys klotho lasted for at least two weeks. They suggest that their findings indicate that giving the protein to monkeys led to cognitive enhancement. A systemic treatment with low doses of Klotho could prove therapeutically effective in the elderly,” say the researchers. More work is needed to find out if it can be given regularly without harm and if it would continue to provide improvements over time. If so , the team hopes that testing will begin with humans, as it could have implications in the future for the treatment of neurodegenerative diseases, such as Alzheimer’s.
Dr. Marc Busche, group leader at the Dementia Research Institute of the United Kingdom, University College London (UCL), is of this opinion, who explains in statements to the Science Media Center: “It is fascinating that a single injection of Klotho can improve cognition in elderly primates for up to two weeks, despite not reaching the brain. The most important next step will be to understand the mechanism underlying this effect. The implications for neurodegenerative diseases, such as Alzheimer’s, are significant, although many questions remain. For example, can Klotho effectively improve cognition in patients when neural systems are already compromised and there is substantial loss of nerve cells and synapses? The non-linear relationship between dose and cognitive improvement, where higher doses did not produce the same improvements, adds an element of surprise and complexity to the findings, and needs to be better understood before moving on to human studies.”
Nabil Djouder, Head of the Growth Factors, Nutrients and Cancer Group at the National Cancer Research Center (CNIO), points out along the same lines at SMC Spain: “it is important to note that it has also been previously published that klotho levels increase in the blood after performing aerobic exercise, indicating that physical exercise may be an alternative to counteract the effects of aging.However, it is important to note that it is not clear what the physiological concentration of klotho would be necessary to obtain positive results.It could be Lower, ‘physiological’ levels in the body need to be reached to achieve a therapeutic margin of cognitive enhancement in humans.”
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