What is Klotho and Can It "Supercharge" the Brain?

Updated April 5, 2019

The race to harness gene splicing and new medicines for the treatment of neurological disorders in the brain has proceeded at a breakneck pace for many years now as scientists look for ways to manage dementia,

Alzheimer’s disease, multiple sclerosis, Parkinson’s disease, and other disorders. It turns out there may be a way to partner this pursuit with brain enhancement treatments that assist with cognition and performance enhancement.

Dr. Dena Dubal of the University of California, San Francisco is one of several researchers studying the nature of a poorly understood but promising hormone called Klotho, which many believe could be the key to unlocking powerful new developments in neurological health.

These scientists are conducting experiments on mice to determine if Klotho can be safely and effectively injected into the human body or if the brain can be triggered to naturally produce high levels of the hormone.

One neuroscientist, Gwendalyn D. King, from the University of Alabama at Birmingham explains the trickiness of understanding Klotho: “You’ve got all of this amazing stuff showing a really major impact, but we can’t really explain why. That’s where we’re stuck.”

What is Klotho?

Klotho was discovered virtually by accident in 1991, when a Japan-based cardiologist Dr. Makota Kuro-o was researching high blood pressure. After introducing DNA to mouse embryos, he realized that the mice had reduced lifespans and deteriorated bodies.

He believed he had inadvertently turned off some gene that is central to controlling the aging process--but he didn’t know what specific genetic trigger was involved.

When Dr. Kuro-o and his colleagues finally identified the cause--a hormone naturally produced in the brain and several other organs, which has a major effect on cognition-- they named it Klotho and began a new series of experiments to breed mice with twice the levels of Klotho.

In 2005, Dr. Kuro-o and his team of scientists produced a paper arguing that higher levels of Klotho likely enhanced the lifespans of mice and that this finding portended promising capabilities of Klotho as treatment for many human brain disorders.

Dr. Dubal picked up on this research and actually enlisted Dr. Kuro-o in her search to find out if higher levels of the Klotho hormone may be fundamentally capable of enhancing human cognition and treating brain disorders. One experiment produced more positive results for mice suffering from Alzheimer’s disease.

Klotho and Genetics in People

What scientists now know is that some people have a genetic propensity to produce more Klotho. After testing the cognition levels of these people, Dr. Dubal and her colleagues published a research paper strongly indicating that the Klotho hormone could help humans (not just mice) with Alzheimer’s disease, other degenerative brain and neurological disorders and increased cognitive abilities.

Other researchers have reported additional findings in recent years that bolster the medical value and the advantages of Klotho that support the argument that it should be further studied so that natural levels can be stimulated in the brain and/or offered as an injection.

These researchers believe that Klotho could become a neurological wonder drug that helps to treat Alzheimer’s disease, multiple sclerosis and Parkinson’s disease.

Klotho may also someday be used as a cognitive enhancement aid for people without neurological disorders, though this usage is more controversial. However, scientists believe there may be no clear dividing line between Klotho as neurological treatment and as an enhancement.

What is APOE e4?

The journey to discovery the medical viability of Klotho hit another unexpected snag when researchers began studying the nature of a genetic variant known as APOE e4, which plays a major role in Alzheimer’s disease. In fact, the gene may make people eight times more likely to develop Alzheimer’s.

Dr. Dubal integrated APOE e4 research into her study of Klotho and found that although people with APOE e4 had the characteristic buildup of clumps affecting their neurological activity, those who also had increased levels of Klotho appeared to be less affected by this genetic catalyst.

Dr. Dubal theorized that Klotho has some kind of natural mechanism for slowing the development of Alzheimer’s and could cause some people to have “biologically younger” brains.

After 15 years of studying Klotho, Carmela Abraham, one of Dr. Dubal’s collaborators, developed a company specifically to study the hormone. Called Klogene Therapeutics, the company seeks to create a new arsenal of medical treatments for people with degenerative neurological brain disorders, using Klothene as the principal agent.

Klotho and Gene-Editing Technologies like CRISPR

These treatments include the gene-editing technology known as Crispr, which could be used to turn neurons into mini-Klotho factories inside the body. In other words, human genetic activity could be modulated to ensure that people naturally produce more Klotho.

Another technique involves Klotho-boosting compounds that could be taken as daily pills.

But not all scientists are totally convinced that this is the right path to be taking, particularly with regards to developing Klotho-enhancing drugs. Dr. King believes that before medications or treatments can be developed, scientists must determine how Klotho interacts with neurons and impacts cellular activity.

“We’ve got a lot of really big observations, and we really need to understand what’s going on at the cell level that would explain them,” King stated.

Dr. King also wants to determine how Klotho specifically affects memory, which is vital to understanding how a hormone would play a role in slowing down the deleterious effects of Alzheimer’s disease. She and her colleagues conducted an experiment on the hippocampus--where memory is created in the brain--of a mouse to see if it’s possible that Klotho could jumpstart the creation of the neurons responsible for harvesting memory.

While there is some disagreement on methodology and timelines, most scientists agree that Klotho is an incredibly promising direction in treating neurological brain disorders. The debate over gene editing is only going to get more heated in the coming decades, as will the concept of using drugs for enhanced cognition. But most people agree that curbing the damage of awful neurological diseases like dementia, Alzheimer’s disease, multiple sclerosis, Parkinson’s disease, and other disorders is an extremely worthwhile pursuit. 

In response to some of the ethical concerns posed, Dr. Dubal framed the issue in a larger context: “We’re going to have 115 million people with Alzheimer’s disease by 2050. If we can make this an effective treatment, then it is unethical not to do so.”

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