2023-07-04 00:02:46
Against mental deterioration: A protein hormone called “Klotho” might counteract mental deterioration in old age, as a test with rhesus monkeys suggests. A single subcutaneous administration of this protein was enough to significantly improve the memory performance of the aging primates for more than two weeks. This result confirms earlier studies with mice and opens up the possibility that this “fountain of youth” protein also works in humans, as the researchers report in “Nature Aging”.
Even without neurodegenerative diseases such as Alzheimer’s or Parkinson’s, mental performance and memory decrease with age. It is true that this reduction can be counteracted by brain training, a healthy lifestyle and an active social life. However, he cannot be prevented entirely. The complexity of both the aging processes and our thinking organ makes it difficult for scientists to find effective and concrete starting points for effective pharmacological countermeasures or therapies.
Protein hormone with promising effects
But in recent years, the so-called Klotho protein has become the focus of aging research. This endogenous protein is located in the cell membrane of various organs, but is also released into the blood as a hormone. Among other things, it influences the insulin balance, the signal chains for certain growth factors and various receptor functions. It is still produced in abundance in newborns and small children, but its level then decreases continuously over the course of life.
The interesting thing, however, is that although this protein hormone cannot cross the blood-brain barrier, it also seems to affect the brain and mental performance: “Studies show that people with increased Klotho levels for genetic or other reasons improve as they age mental performance, delayed neuropathological symptoms and a reduced risk of senile dementia and Alzheimer’s disease,” report Stacy Castner of Yale University in New Haven and her colleagues.
Tests with mice have also shown that administration of the Klotho protein via syringe also has a mentally rejuvenating effect: the old animals showed better mental performance, increased synaptic plasticity and a reduced risk of Alzheimer’s and other forms of dementia.
Aging rhesus monkeys as a test case
Could this “fountain of youth” protein also help once morest mental deterioration in humans? To find out, Castner and her team first investigated this in rhesus monkeys. “Rhesus monkeys are 93 percent phylogenetically identical to humans, have similar genetic diversity and demonstrate higher cognitive functions,” explains the team. “Like humans, rhesus monkeys experience mental degradation and synaptic changes in various brain regions, including the hippocampus and prefrontal cortex, with aging.”
For their study, the researchers gave 18 elderly rhesus monkeys a single dose of ten micrograms of protein per kilogram of body weight, injected under the skin. Before and at regular intervals followingwards, they had the rhesus monkeys complete memory tests. The monkeys had to remember in which of up to nine identical looking containers a piece of food had been placed. These tests were conducted at different levels of difficulty.
Lasting effect following a single dose
The result: just four hours following the Klotho injection, the senior rhesus monkeys began to see the first effects. Monkeys performed significantly better than before in the memory tests. In contrast, this was not the case in control animals that had only received a saline solution. The positive effect on the memory performance of the rhesus monkeys also lasted for at least two weeks. This was particularly evident in the tasks that made more demands on the brains of the aging animals.
“Taken together, our data provide evidence that giving Klotho can improve mental performance in aging rhesus monkeys,” Castern and her colleagues write. This effect lasts well beyond the half-life of the protein in the blood. This might indicate that this protein causes longer-lasting changes in brain metabolism and other functions important for cognitive performance.
Similar positive effects are also possible in humans
According to Castern and her team, these results suggest that humans might also benefit from treatment with the Klotho protein. Restoring the normal childhood levels of this hormone in the blood seems to hold particular promise. Because additional tests with a higher dose of 20 and 30 micrograms of Klotho per kilogram of body weight did not bring any improvements compared to the lower dose.
“A systemic low-dose Klotho treatment might prove to be therapeutically effective in aging people,” say the researchers. Before this can happen, however, further questions must first be clarified, they emphasize. So far it has not been clarified which “messengers” the Klotho protein uses to influence brain functions, because it does not penetrate into the brain itself. In addition, it was to be investigated whether even lower concentrations of this protein might also have an effect and how long the effect lasts at most. (Nature Aging, 2023; doi: 10.1038/s43587-023-00441-x)
Quelle: Nature Aging
July 4, 2023
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