the protein that longevity laboratories want to inject in the future

In 1997, the Japanese doctor and researcher Makoto Kuro-o made a mistake in the laboratory where he carried out his experiments. I was trying to create mice with hypertension when the genetic material he manipulated was inserted in the wrong place and altered an unknown gene. The resulting mice aged at an astonishing rate: in just two months they had arteriosclerosis, osteoporosis, cognitive decline and wrinkled skin. The normal thing is for a mouse to live almost three years, but those animals would live much less.

After four years of investigating what had gone wrong, Kuro-o identified the gene responsible and published his discovery in Nature. called him klotho in honor of Clotho, the Greek goddess who spins the thread of life. He had discovered, by accident, one of aging suppressants most powerful known.

The protein klotho It exists in two versions. One is anchored to the membrane of kidney and brain cells. The other is a fragment that breaks off from the membrane, enters the bloodstream and travels throughout the body acting as a signal of systemic health. The problem is that its levels fall constantly with age in both humans and all primates that have been studied. The interesting thing is that this is not at all a biological coincidence: it is a mechanism that has direct consequences on our aging.

A very powerful weapon against aging

The most relevant experiment so far He published it in 2025 an international team of researchers from the Institute of Neurosciences of the Autonomous University of Barcelona led by Professor Miguel Chillón. These scientists treated mice with gene therapy in order to get their own cells to produce more klotho. At 24 months (equivalent to about seventy human years) the results were notable: the treated animals lived between 15 and 20% longer with better muscle mass, greater bone density, less fibrosis and better cognitive function.

In the hippocampus, the area of ​​the brain where memory resides, the treatment stimulated the generation of new neurons. A 20% longer lifespan in mice is, in aging biology, an extraordinary result. Have klotho in blood is important because this protein acts on several of the most damaging processes derived from aging. In the kidney it regulates how the body manages phosphorus. In fact, without klotho Phosphorus accumulates and accelerates cellular deterioration.

And in the rest of the body it reduces oxidative stress, stops chronic inflammation, activates FOXO3A (one of the most studied longevity genes) and inhibits cellular senescence, which is the state in which aged cells stop functioning well but do not die and slowly poison the tissue around them. Be that as it may, the biggest challenge is to find a way to transfer all this knowledge to human beings.

In mice, viral vectors were used, injected both into a vein and directly into the brain, a combination that carries significant risks in people. The alternative is administer protein directly as a drug, but finding a system that keeps it stable and delivers it effectively to its target organs (the kidney, brain, muscles and bones) remains an unsolved problem.

Still, the longevity biotech industry has decided not to wait. The American startup Minicircle, in which Sam Altman and Peter Thiel have investedbegan a phase 1 clinical trial with 24 participants in October 2025 to test a gene therapy for klotho based on plasmids: DNA fragments that do not integrate into the chromosome and whose effects last approximately one year. This therapy is not approved by the FDA (Food and Drug Administration), so it operates through international clinics.

However, the applications pursued by the industry go beyond aging in healthy people. Klotho Neurosciences has programs underway to combat Alzheimer’s, amyotrophic lateral sclerosis and cardiovascular diseases, with phase I and II trials planned between 2027 and 2028. BioVivaon the other hand, has identified improvements in cognitive tests in patients with dementia treated with a combined gene therapy of klotho and telomerase. and the company Avaí Bio works with modified encapsulated cells that overexpress the protein. He plans to have his first results ready for the Second Annual Klotho Conference in September 2026.

Everything we have seen in this article looks very good, but we must not overlook that the solid life extension data comes from mice, and the history of the biology of aging is full of spectacular findings in animals that have not been transferred to humans with the same success. Furthermore, several important unanswered questions remain on the table: what effects does overexpression of klotho in the long term, whether the timing of its administration matters in both people and rodents or what happens to phosphorus metabolism and vitamin D after years of treatment.

Still, for the first time we have clinical trials, there is private capital moving on a large scale, and there is an annual conference dedicated exclusively to this protein. Klotho is, ultimately, one of the most promising weapons that biology has put in our hands to deal with our aging.

Image | Alirio García on Unsplash

More information | Nature | UAB

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