Protein Breakthrough Could Extend Healthy Lifespan, Study Finds
Published in Molecular Therapy and led by Professor Miguel Chillón, the study found that a specific form of Klotho, known as secreted Klotho (s-KL), improved muscle strength, bone health, and brain function in treated mice. These mice lived 15–20% longer than untreated peers, reaching the human equivalent of about 70 years with greater physical and mental vitality.
Klotho is known to combat inflammation and oxidative stress, key drivers of aging. Unlike other forms of the protein, s-KL circulates freely in the body without disrupting systems like calcium metabolism, making it a safer candidate for therapies.
'If we can find a viable delivery method, s-KL could make a significant contribution to improving people's quality of life,' the researchers said, per The Brighter Side of News. 'It could help build the healthiest society possible.'
Using gene therapy with adeno-associated viruses (AAV9), scientists delivered s-KL through the bloodstream and directly into the brain, targeting areas critical for muscle and memory. Three groups of mice were treated: one at six months (young adulthood), another at 12 months (middle age), and a control group.
By 24 months, treated mice showed stronger muscles with larger fibers, less fibrosis, and enhanced repair by satellite cells. Bone structure, particularly in females, remained more intact, suggesting protection against osteoporosis.
'KL treatment improved physical fitness, related to a reduction in muscle fibrosis and an increase in muscular regenerative capacity,' the researchers noted, The Brighter Side reported.
In the brain, s-KL promoted new neuron growth in the hippocampus, the memory center, and boosted immune processes like phagocytosis, where cells clear toxic waste. This cleanup is vital as aging glial cells often fail to remove debris, contributing to cognitive decline. Transcriptomic analysis revealed increased gene activity tied to immune response and brain cell regeneration.
'We now have viral vectors that can reach the brain after being administered intravenously, which would make it easier to safely transfer this therapy to humans,' said Joan Roig-Soriano, the study's first author, per The Brighter Side.
The findings aim to extend health span — the years spent in good health — rather than just lifespan. The team has filed patents for using Klotho to support cognition, strengthen bones and muscles, and increase longevity. While gene therapy was used in the study, direct protein delivery as a drug is also being explored, though a reliable method to target tissues without side effects is still needed.
With global populations aging — experts predict a quarter of people in developed countries will be over 65 by 2060 — such treatments could ease the burden on health systems by preventing age-related diseases before they start. The study's results suggest Klotho could redefine aging, offering a future where decline is not inevitable.
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