Our fight against aging has a new ally, and it has a name that evokes Greek myth. Klotho, like the goddess who spun the thread of life, seems able to lengthen that thread and make it more resistant. This is demonstrated by a study published in Molecular Therapy by an international team led by Professor Miguel Chillón of the Autonomous University of Barcelona.
Through a gene therapy that increases the levels of the secret way of this protein (s-KL), the researchers obtained results that to define as promising is an understatement: mice that live up to 20% longer, with stronger muscles, healthier bones and more active brains. But, as I always repeat, it's not just a question of quantity of life.
The origin of an extraordinary discovery
The name Klotho is not a coincidence: it directly recalls the youngest of the three Moirai of Greek mythology (those that we call Parcae), the very one who he wove the thread of human life. An appropriate choice for a protein that, as numerous studies are demonstrating, could play a fundamental role in regulating our longevity.
The Klotho protein was first discovered in 1997 by Japanese researcher Makoto-Kuro, that published in Nature the results of his experiments. Already then, mice deficient in this protein showed signs of premature aging, while those with higher levels seemed to enjoy greater longevity and healthier aging.
More than 25 years have passed since that first discovery, and today research has made great strides. I am particularly struck by the evolution of this field of study: we have moved from observing a phenomenon to understanding the cellular mechanisms underlying it, up to potential therapeutic applications.
Klotho, a radical approach to aging
The study led by Professor Chillón is a turning point. The researchers, as mentioned, used gene therapy vectors to introduce into the cells of young mice the gene encoding the secreted form of the Klotho protein (s-KL). This caused the cells to begin producing the protein on their own, significantly increasing its levels in the blood.
The results were surprising. Mice treated with s-KL They lived 15 to 20 percent longer than others. To give you an idea, this would be like extending the average human lifespan from the current 80 years to about 96 years. But perhaps more importantly, it's not just about living longer: these animals showed better physical performance, with larger muscle fibers and less fibrosis, indicating better muscle health.
“We have been working with the protein Klotho for some time, due to its therapeutic potential in the treatment of neurodegenerative diseases. In this study, we wanted to see if s-KL could also be beneficial for healthy aging by examining a wide range of factors,” explains Miguel Chillón.
The amazing effects of Klotho on the whole organism
The beauty of this discovery is its systemic nature. It is not a treatment that improves a single aspect of aging, but an intervention that appears to have beneficial effects on multiple fronts simultaneously.
In addition to the muscles, significant improvements were also observed in the bone health, particularly in females, with greater preservation of the internal structure of the bones (trabeculae). This suggests, for example, a potential protective effect against osteoporosis, a major concern in human aging.
But that's not all. In the brain, s-KL treatment promoted the generation of new neurons and increased immune activity in the hippocampus, suggesting possible cognitive benefits. Transcriptomic analysis revealed increased phagocytosis and immune cell activity in the aged hippocampus, which may translate into improved protection against age-related cognitive decline.
From Greek Mythology to the Future of Medicine
What makes this research particularly fascinating is the bridge it creates between ancient mythology and cutting-edge science. Klotho, in Greek mythology, was the one who spun the thread of human life, partly determining its duration. Today, science shows us that the protein that bears her name could actually influence the duration and quality of our life.
The research group had already patented the use of Klotho to treat cognitive deficits, and following this study, three new patents were filed. These protect the use of Klotho for the treatment of bone and muscle deficits, as well as for the development of therapies aimed at increasing longevity.
Future prospects
Of course, it is important to remember that this research was conducted on mice, and the transition to humans will require further in-depth studies. However, the potential is enormous.
As the research team states:
“Once we have developed a viable delivery method, s-KL could make a significant contribution to improving people’s quality of life and helping to build the healthiest society possible.”
Scientists continue to explore whether direct delivery of the protein or more refined gene therapy options might work better for humans, and they plan to further study how s-KL integrates into different biological pathways.
It is a historic moment in which the world population is rapidly aging, with all the health and social challenges that this entails. Other research, such as that oninterleukin 11, are opening new avenues towards understanding the mechanisms of aging and the possibility of modulating it.
The prospect of an intervention that can simultaneously improve multiple aspects of aging offers real hope for a future in which we not only live longer, but do so while maintaining a better quality of life.
