After more than 30 years since its identification as a crucial “longevity gene,” the protein klotho has been successfully used to enhance the cognitive function of aging rhesus macaques, a development that sets the stage for human trials.
Building on recent studies involving mice models, an international team of scientists, including researchers from the University of California, San Francisco, Weill Institute for Neurosciences, administered klotho protein injections to 18 rhesus macaques (Macaca mulatta) with an average age equivalent to around 65 in humans. The results revealed improved working memory and task completion abilities in the monkeys.
During the study, the macaques were required to navigate easy and challenging mazes repeatedly to find a treat, testing their ability to recall the most direct paths. The tasks were repeated four hours later after the administration of klotho, which increased protein levels to that of juvenile levels. The monkeys demonstrated an average improvement of 6% for the easy mazes and around 20% for the more difficult task. The memory enhancement lasted for at least two weeks. Notably, the dosage used in the macaque study was significantly lower than that used in previous mouse trials.
Klotho is a transmembrane protein family consisting of three subfamilies, with alpha-klotho being the most commonly referenced. Its identification took place in 1997, and its functions are still not fully understood. However, it plays a crucial role in aging, regulating various pathways such as phosphate levels and insulin signaling.
The protein, named after the Greek goddess Clotho, who spun the thread of human life, is naturally produced in the kidneys and declines with age. Its deficiency contributes to arterial stiffening, hypertension, vascular degeneration, and other age-related health conditions. Previous studies have demonstrated how boosting klotho expression improves cognitive function in mouse models, including the influence of intermittent fasting on klotho levels and the regenerative effects of plasma transfusions from younger to older animals.
Dena Dubal, one of the co-authors of the current study, likens the cognitive tests to real-world scenarios, such as remembering the location of a parked car or recalling a series of numbers—skills that tend to decline with age. Dubal, who is now a physician-researcher at the University of California, San Francisco’s Weill Institute for Neurosciences, has been investigating the potential of klotho to extend lifespan for several years.
Dubal stated in 2018, “For humans, the ultimate goal is really how we can increase our ‘healthspan.’ And that may go hand in hand with an increase in lifespan because the things that help us live longer are also the things that help us live better.”
While many aspects of klotho’s restorative abilities remain unknown, Dubal emphasizes that this research provides a compelling reason to proceed with human clinical trials.
** Taking lead from NEW ATLAS