The truth about klotho, the so-called longevity protein

Aging is inevitable. For some, it's a blessing, synonymous with a long life full of meaningful experiences. For many others, it’s a monster to fight by any means necessary. The reality lies somewhere in between. No one wants wrinkles, loss of energy and strength, memory disorders, bone fragility, hearing loss, and all the other ailments associated with old age. So, periodically, a new remedy emerges, promising a flexible, athletic body free of diseases. In recent years, the focus of all aspiring Benjamin Buttons has been on klotho, a protein believed to be involved in slowing down aging and potentially contributing to overall better health. Is this really the modern version of the fountain of youth? Some studies seem to indicate it, but science has yet to reach a definitive conclusion. Let's see what is known so far about the so-called longevity protein.

What is klotho

In 1997, Makoto Kuro-o, a researcher at Jichi Medical University, and his team were studying hypertension in mice when they noticed that a group of mice aged more rapidly and had a shorter lifespan. The cause of this rapid degeneration was a protein—or more precisely, a family of transmembrane proteins—encoded by a gene on chromosome 13 and produced mainly in parts of the kidney and a network of vessels in the brain known as the choroid plexus. It exists both in membrane-bound and soluble forms. A deficiency of this protein has been associated with kidney problems, cardiovascular diseases, cancer, neurological issues like cognitive deficits and Alzheimer's disease, lung, bone, and metabolic problems such as osteoporosis and diabetes. It is therefore hypothesized to play a key role in slowing down aging and combating various age-related diseases. For this reason, it was named klotho, inspired by one of the three Moirai from Greek mythology, who spins the thread of life, determining, along with her sisters, each person’s destiny.

Klotho, the studies

After more than twenty years of considering klotho proteins as the secret to longevity, two studies published in Nature in 2018 (one by a team of researchers from Yale University and the other from New York University) demonstrated that these proteins simply help a family of hormones called Fgfs (or fibroblast growth factors), which regulate the metabolic processes of many organs, including the liver, kidneys, and brain, to mediate their anti-aging action. However, they discovered that when the beta-Klotho protein binds to FGF21, it stimulates insulin sensitivity and hormonal metabolism, causing weight loss. This opens up potential ways to exploit klotho in targeted therapies for conditions like diabetes, obesity, and certain types of cancers. A more recent study has shown that a relatively low dose of klotho, already tested on mice, has the ability to enhance synaptic and cognitive functions, such as memory, in elderly monkeys. Experts consider this a significant result because it suggests that "replenishing klotho might be therapeutic in aging humans as well." Other researchers suspect that klotho acts as a sort of anti-inflammatory protein, which could play a role in protecting the brain from inflammatory neurological diseases and neurodegenerative conditions. Finally, a study published in Scientific Reports in 2023 analyzed the relationship between the protein and physical functions in a group of healthy adults, not confirming the correlation between its levels, muscle strength, and other functional indicators. However, it did confirm that its levels decrease with age, starting as early as 50, making it a useful and early warning signal for age-related diseases.

Is klotho our elixir of life?

Research is still ongoing, and it’s too early to call klotho the longevity protein or get carried away with enthusiasm. Aging is a complex process involving multiple pathways and governed by many more molecules than just klotho. The data seems to indicate that klotho plays an important role in all of this, but how to exploit it to address some age-related issues is still unclear. Nor is it known how to increase its presence in the body. Simply ingesting or injecting the protein doesn’t seem to work, and scientists are experimenting with other possible solutions, including stimulating its natural release through diet or exercise.