Injecting Monkeys with a Protein known as klotho, referred to as a ‘longevity factor,’ has the potential to enhance their cognitive abilities as revealed by a recent study. The research, published in Nature Aging on 3rd July, offers promising prospects for the development of novel therapies targeting neurodegenerative disorders. Remarkably, this study demonstrates, for the first time, the cognitive improvement in primates. Which results from the restoration of klotho levels, a protein that naturally declines with age. Previous investigations in mice indicated that klotho injections not only extended their lifespan but also enhanced synaptic plasticity. The capacity to regulate neural communication at synapses, the junctions between neurons.
Marc Busche, a neurologist from the UK Dementia Research Institute group at University College London. He suggests that the close genetic and physiological similarities between primates and humans imply potential applications for treating cognitive disorders in humans. The protein derives its name from Clotho, one of the Fates in Greek mythology, who spins the thread of life.
To evaluate the cognitive abilities, a group of aged rhesus macaques (Macaca mulatta), with an average age of approximately 22 years, underwent memory tests before and after receiving a single injection of klotho. The cognitive assessment involved a behavioural experiment to assess spatial memory. The monkeys were required to recall the location of a hidden edible treat, placed in one of several wells by the investigator.
Dena Dubal, a physician-researcher at the University of California, San Francisco and a co-author of the study. They draw a parallel between this test and remembering the location of one’s parked car or recalling a sequence of numbers after a brief period. These tasks tend to become more challenging with age.
Following the administration of klotho, the monkeys exhibited significant improvement in the memory tests. Prior to the injections, they correctly identified the wells around 45% of the time. Whereas after the injection, the success rate increased to approximately 60%. This positive effect endured for a minimum of two weeks. Notably, unlike previous studies involving mice, relatively low doses of klotho proved to be effective. This complexity in the findings suggests a more nuanced mode of action than previously assumed, according to Busche.
The precise mechanism by which klotho injections impact cognition and its enduring effects remain unclear. Klotho, in itself, cannot penetrate the blood-brain barrier, and uncovering the underlying mechanism requires identifying the intermediates involved, explains Dubal. Nevertheless, this study instills hope and provides a compelling rationale for initiating human clinical trials.
Gøril Rolfseng Grøntvedt, a neurologist at the Norwegian University of Science and Technology in Trondheim. He concurs that further investigations are necessary to address these unanswered questions. Grøntvedt and her team have previously discovered that individuals with Alzheimer’s who naturally possess higher klotho levels tend to experience less cognitive decline compared to those with lower levels. This observation raises the possibility that artificially augmenting klotho levels could yield beneficial effects. A comprehensive understanding of the protein’s mode of action holds immense significance in realizing its full clinical potential, emphasizes Grøntvedt.