An international study, published in Molecular Therapy in May 2025, demonstrates that increasing levels of the Klotho protein can extend lifespan and improve physical and cognitive health during aging, using mice as a model. The research, led by Professor Miguel Chillón at the Institut de Neurociències at the Universitat Autònoma de Barcelona (INc-UAB), highlights the potential of Klotho as a therapeutic target for promoting healthier aging in humans.
The study involved treating young mice with gene therapy vectors to stimulate their cells to secrete more of the soluble form of Klotho protein (s-KL). At 24 months, roughly equivalent to 70 human years, these mice showed improved muscle, bone, and cognitive health. Treated mice lived 15-20% longer and exhibited better physical performance, larger muscle fibers, and reduced fibrosis, indicating enhanced muscle health. Improvements in bone health were also noted, particularly in females, suggesting a protective effect against osteoporosis.
In the brain, s-KL treatment promoted the generation of new neurons and increased immune activity in the hippocampus, suggesting possible cognitive benefits. These findings build upon previous research indicating that Klotho levels decline with age and are associated with age-related diseases. Overexpression of the Klotho gene has been shown to lengthen lifespan in mice, raising the possibility of utilizing Klotho to control or reverse aging and/or neurodegeneration. Further research is needed to determine if similar results can be achieved in humans.