Klotho Protein: Is It the Key to Healthier, Longer Lives?

 Klotho Protein: Is It the Key to Healthier, Longer Lives?

A new international study led by the Institut de Neurociències at Universitat Autònoma de Barcelona (INc-UAB) has uncovered something remarkable: boosting levels of the Klotho protein in mice doesn’t just add years to their lives—it makes those years better, both physically and mentally.

Aging usually comes with a long list of setbacks—muscles shrink, bones weaken, and the risk of falls and injuries skyrockets. In the brain, neurons start breaking down and losing touch with each other, paving the way for diseases like Alzheimer’s and Parkinson’s. With more and more people living longer, finding ways to slow or even reverse these changes is one of the toughest problems science faces today.

Published in Molecular Therapy, the research, led by Professor Miguel Chillón, an ICREA researcher at INc-UAB, examined what happens when mice are given extra doses of the secreted version of Klotho (s-KL). Using gene therapy, the team got the animals’ own cells to pump out more of the protein. By the time the mice reached 24 months old (roughly 70 in human years), they weren’t just living longer—they were stronger, sharper, and healthier.

“We’ve been interested in Klotho for a while because of its potential to treat neurodegenerative diseases,” Chillón said. “This time, we wanted to see if s-KL could help with overall healthy aging, so we looked at a little bit of everything.”

The results? Mice with higher s-KL levels lived 15-20% longer than normal mice. They ran faster, had more significant and healthier muscle fibers, and showed less muscle scarring—signs of improved muscle health. Female mice, in particular, kept their bone structure better, hinting that s-KL might help guard against osteoporosis. And in the brain, the Klotho boost led to more new neurons and ramped-up immune activity in the hippocampus, a region crucial for memory.

How did the team pull it off? They used viral vectors—essentially tiny delivery vehicles for genes—to sneak the Klotho gene into the mice’s bodies. Some were injected straight into the bloodstream, others directly into the brain, ensuring the right cells got the message to start making s-KL. “We now have viral vectors that can reach the brain just through an IV,” explained Joan Roig-Soriano, first author of the study. “That could make it much easier to bring this therapy to people. Or maybe we’ll just deliver the protein as a drug, though we still have to figure out how to get it where it needs to go.”

The team had already locked in a patent covering Klotho for tackling cognitive decline. Now, they’ve filed three more patents: one for using Klotho to treat muscle loss, another for bone issues, and a third for therapies that could lengthen lifespan.

“If we can solve the delivery problem, s-KL could seriously improve quality of life as people age,” the researchers said. “It’s a step toward building a healthier future for everyone.”