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People possessing a variant of the longevity gene KLOTHO have demonstrated enhanced brain skills, regardless of factors such as age, sex or risk of Alzheimers 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 brains nerve cell connections, the study authors explained.

This could be a major step toward helping millions around the world who are suffering from Alzheimers 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 brains 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 Alzheimers 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.

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Variant Of Longevity Gene Could Enhance Cognitive Abilities

Short height and long life have a direct connection in Japanese men, according to new research based on the Kuakini Honolulu Heart Program (HHP) and the Kuakini Honolulu-Asia Aging Study (HAAS).

"We split people into two groups -- those that were 5-foot-2 and shorter, and 5-4 and taller," said Dr. Bradley Willcox, one of the investigators for the study and a Professor in the University of Hawai`i (UH) John A. Burns School of Medicine's Department of Geriatric Medicine. "The folks that were 5-2 and shorter lived the longest. The range was seen all the way across from being 5-foot tall to 6-foot tall. The taller you got, the shorter you lived."

Researchers at the Kuakini Medical Center, the UH John A. Burns School of Medicine and U.S. Veterans Affairs worked on the study, which was recently published in PLOS ONE, a peer-reviewed medical journal.

The researchers showed that shorter men were more likely to have a protective form of the longevity gene, FOXO3, leading to smaller body size during early development and a longer lifespan. Shorter men were also more likely to have lower blood insulin levels and less cancer.

"This study shows for the first time, that body size is linked to this gene," said Dr. Willcox. "We knew that in animal models of aging. We did not know that in humans. We have the same or a slightly different version in mice, roundworms, flies, even yeast has a version of this gene, and it's important in longevity across all these species."

Dr. Willcox noted that there is no specific height or age range that should be targeted as a cut-off in the study, in part because "no matter how tall you are, you can still live a healthy lifestyle" to offset having a typical FOXO3 genotype rather than the longevity-enhancing form of the FOXO3 gene.

The Kuakini HHP started in 1965 with 8,006 American men of Japanese ancestry born between the years 1900 and 1919. The lifestyles and health conditions of these men were closely followed and studied by the researchers through the years. The Kuakini HHP is the only longitudinal study of Japanese-American men that has included epidemiological and clinical data of the cohorts for almost 50 years. From a worldwide perspective, it is the only research program that maintains a comprehensive, longitudinal database of demographic, lifestyle and medical information, as well as biological specimens collected, from such a large cohort of aging men.

"One of the reasons why Honolulu is perfect for this kind of study is that we have the longest-lived state in the country, combined with a population that has remained, for the most part, in Hawaii. This has helped us maintain one of the longest-running, largest studies of aging men in the world, in the Kuakini Honolulu Heart Program," Dr. Willcox said.

Approximately 1,200 men from the study lived into their 90s and 100s, and approximately 250 of those men are still alive today.

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Shorter men live longer, study shows