brain boosting genetic variant
May 12, 2014

Variant Of Longevity Gene Could Enhance Cognitive Abilities

[ Watch the Video: Longevity Gene May Boost Brain Power ]

redOrbit Staff & Wire Reports - Your Universe Online

People possessing a variant of the longevity gene KLOTHO have demonstrated enhanced brain skills, regardless of factors such as age, sex or risk of Alzheimer’s disease, according to research published in the journal Cell Reports.

The National Institutes of Health-funded study found that people with the variant had improved thinking, learning and memory. It also revealed that increasing levels of the KLOTHO gene in mice made the creatures smarter, possibly by increasing the strength of the brain’s nerve cell connections, the study authors explained.

“This could be a major step toward helping millions around the world who are suffering from Alzheimer's disease and other dementias,” lead author Dr. Dena Dubal, the David A. Coulter Endowed Chair in Aging and Neurodegeneration at the University of California San Francisco School of Medicine, said in a statement. “If we could boost the brain's ability to function, we may be able to counter dementias.”

According to the study authors, the effects that aging has on the brain will become a greater health issue as people live longer, especially when it comes to the set of brain disorders known as dementias. The symptoms of dementia include impaired language skills and memory issues, and the number of cases is expected to double every 20 years. By the year 2050, over 115 million people worldwide are expected to require treatment for one of these conditions.

People who have one copy of a variant of the KLOTHO gene known as KL-VS are more likely to live longer and are also less likely to suffer a stroke, the researchers said. On the other hand, people who have two copies of the gene are more likely to live shorter lives and have a higher risk of stroke.

As part of their new study, Dr. Dubal and her colleagues discovered that men and women who possessed one copy of the KL-VS variant performed better on a series of different cognitive examinations than those who lacked the gene – regardless of how old they were, whether they were male or female, or whether or not they had the apolipoprotein 4 gene (the primary genetic risk factor for Alzheimer's disease).

The investigative team recruited over 700 subjects between the ages of 52 and 85, none of whom demonstrated signs of dementia, and tested several different cognitive abilities during three studies. Between 20 and 25 percent of all subjects had one copy of the KL-VS variant, and those individuals outperformed those who had no copies on the various tests, according to the study authors.

“This study shows the importance of genes that regulate the multiple aging processes involved in the maintenance of cognitive function,” said Dr. Suzana Petanceska, of the National Institute on Aging (NIA) Division of Neuroscience. “Understanding the factors that control the levels and activity of KLOTHO across multiple organ systems may open new therapeutic avenues for prevention of age-related cognitive decline and dementia.”

The KLOTHO gene also provides the blueprint for the klotho protein, which is made by cells found in the kidney, placenta, small intestine, and prostate. The researchers found that performance on the cognitive tests decreased with age, regardless of whether a subject had one or no copies of the KL-VS gene variant, and they believe that an age-related decrease in circulating levels of this protein could be partially responsible.

“These surprising results pave a promising new avenue of research,” said Dr. Roderick Corriveau, program director at NIH's National Institute of Neurological Disorders and Stroke (NINDS). “Although preliminary, they suggest that a form of klotho could be used to enhance cognition for people suffering from dementia.”

The study authors genetically engineered mice to produce an overabundance of the klotho protein in order to test their hypothesis. They found that the klotho-enhanced mice lived longer and had higher levels of the protein both in the blood and the hippocampus, a region of the brain that controls some types of memory and learning.

“Similar to human studies, the klotho-enhanced mice performed better on a variety of learning and memory tests, regardless of age. In one test, the mice remembered the location of a hidden target in a maze better, which allowed them to find it twice as fast as control mice,” the NIH explained.

“Overall our results suggest that klotho may increase cognitive reserve or the brain's capacity to perform everyday intellectual tasks,” added senior author Dr. Lennart Mucke, the director of the Gladstone Institute of Neurological Disease in San Francisco, as well as a neuroscience and neurology professor at UCSF.