The longevity gene improves brain function
Researchers at the National Institute for the Study of Neurological Disorders and Stroke in the USA, working under the guidance of Professor Lennart Mucke, have found that one of the variants of the klotho gene affecting life expectancy provides not only longevity, but also good brain function. This is manifested by an improvement in thinking abilities, learning ability and memory, regardless of age, gender and the presence of genetic factors predisposing to Alzheimer's disease. Moreover, increasing the expression of the klotho gene in mice makes animals smarter, possibly by strengthening connections between brain neurons.
Klotho is the "spinning thread of life" goddess of fate from Greek mythology, whose name was given to the gene that determines a person's longevity. Earlier studies have shown that in a heterozygous state (1 copy inherited from one of the parents), one of the variants of this gene, known as KL-VS, increases a person's life expectancy and reduces the risk of stroke. At the same time, the presence of two copies of this allele in the genome has the opposite effect.
The authors demonstrated that, in addition to the already known advantages, one copy of KL-VS is associated with the best results obtained when performing a whole set of tests for cognitive abilities, regardless of gender, age, as well as the presence in the genome of the apolipoprotein-4 gene, which is the main genetic risk factor for Alzheimer's disease.
In total, more than 700 people aged 25 to 85 years participated in the three conducted studies. None of them showed symptoms of dementia. According to the previously obtained population data, 20-25% of the participants had one copy of the KL-VS allele. When performing tests on learning, memorization and the ability to concentrate, these participants consistently showed higher results than participants with two copies or no KL-VS allele at all.
The protein product of the klotho gene is synthesized mainly by cells of the kidneys, placenta, small intestine and prostate gland. A shortened version of this protein can circulate in the circulatory system. Analysis of blood samples showed that the presence of one copy of the KL-VS allele in the genome corresponds to a higher concentration of the klotho protein in the bloodstream. In accordance with earlier data, an age-related decrease in this concentration was demonstrated. The researchers suggested that this may be one of the reasons for the deterioration of cognitive ability testing results observed in older people.
To test this hypothesis, they created genetically modified mice whose cells produced an excessive amount of klotho protein. These animals were distinguished by a long lifespan and elevated levels of klotho in the blood and hippocampus, a region of the brain involved in learning and memory processes. They also, regardless of age, showed the best results when performing learning and memorization tasks. For example, in the maze cache memorization test, they found the cache twice as fast as the control group animals.
It is generally believed that learning enhances the interaction between nerve cells of the brain by increasing the strength of interneuronal contacts or synapses. The data obtained during the registration of electrical impulses indicate that klotho helps to increase the strength of synapses in the process of learning and memorization.
The study of animal synapses showed that higher levels of klotho corresponded to a greater number of GluN2B subunits, which are components of ionotropic glutamate receptors selectively binding N-methyl-D-aspartate (NMDA) and providing interneuronal interaction in many glutaminergic synapses. The administration of a drug to animals selectively blocking NMDA receptors containing GluN2B subunits worsened the results they demonstrated when testing the level of cognitive functions. This indicates the potential for improving cognitive abilities through manipulation of the corresponding NMDA receptors.
The authors believe that their results will be able to help millions of people suffering from Alzheimer's disease and other forms of dementia in the future.
Article by Dena B. Dubal et al. Life Extension Factor Klotho Enhances Cognition is published in the journal Cell Reports.
Evgeniya Ryabtseva
Portal "Eternal youth" http://vechnayamolodost.ru based on the materials of the National Institutes of Health:
Longevity gene may boost brain power.
13.005.2014