Published on: May 07, 2025
As we age, it's common to experience a decline in muscle and bone mass, leading to increased frailty and a higher risk of falls and serious injuries. At the same time, cognitive decline occurs as neurons gradually deteriorate and lose connections, while neurodegenerative diseases such as Alzheimer’s and Parkinson’s become more widespread. In a society with an aging population, mitigating these effects has become a major focus of scientific research.
A recent article in Molecular Therapy details a breakthrough led by Professor Miguel Chillón, an ICREA researcher at the Institut de Neurociències of the UAB (INc-UAB), in collaboration with an international team. The researchers found that elevating levels of the secreted form of the Klotho protein (s-KL) in mice significantly improved aging outcomes. Using gene therapy vectors, they treated young mice to boost their natural secretion of s-KL. By 24 months of age—comparable to around 70 human years—these treated mice exhibited better muscle strength, bone density, and cognitive performance.
We’ve been exploring the therapeutic potential of Klotho in neurodegenerative conditions for a while. In this study, we wanted to understand whether s-KL could also promote healthier aging more broadly, said Prof. Chillón.
The results were striking: mice receiving the s-KL treatment lived 15–20% longer, had better physical capabilities, larger and healthier muscle fibers with reduced fibrosis, and showed improved bone structure—particularly in females, where internal bone architecture (trabeculae) was better preserved, pointing to a possible defense against osteoporosis. In the brain, s-KL boosted the creation of new neurons and enhanced immune activity in the hippocampus, indicating potential cognitive benefits.
The gene therapy approach involved delivering the s-KL gene via viral vectors into the bloodstream and directly into the brain, enabling the animals’ own cells to produce the protein. We now have viral vectors that can cross into the brain through intravenous administration, which could simplify the process of bringing this therapy to humans, explained Joan Roig-Soriano, INc-UAB researcher and lead author of the study. Another approach could be delivering the protein itself as a drug, though we still need to develop effective delivery methods to ensure it reaches target tissues.
The team had already secured a patent for using Klotho to treat cognitive disorders, and this new research has resulted in three additional patents—covering applications for muscle and bone degeneration, as well as general longevity-enhancing therapies.
“If we can develop an efficient delivery system, s-KL has the potential to meaningfully improve quality of life and support the development of a healthier aging population,” the researchers concluded.
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