Scientists showed that people who have a variant¹ of a longevity² gene³, called KLOTHO, have improved brain skills such as thinking, learning and memory regardless of their age, sex, or whether they have a genetic⁴ risk factor for Alzheimer's disease. Increasing KLOTHO gene levels in mice made them smarter, possibly by increasing the strength of connections between nerve cells in the brain. The study was partly funded by the National Institutes of Health.

 

"This could be a major step toward helping⁵ millions around the world who are suffering from Alzheimer's disease and other dementias," said Dena Dubal, M.D., Ph.D., an assistant professor of neurology, the David A. Coulter Endowed Chair in Aging and Neurodegeneration at the University of California San Francisco (UCSF) and the lead author of the study published in Cell Reports. "If we could boost the brain's ability to function, we may be able to counter dementias."

 

As people live longer the effects of aging on the brain will become a greater health issue. This is especially true for dementias, a collection of brain disorders⁶ that can cause memory problems, impaired⁷ language skills and other symptoms. With the number of dementia cases worldwide estimated to double every 20 years from 35.6 million people in 2010 to 65.7 million in 2030 and 115.4 million in 2050, the need for treatments is growing.

 

Klotho is the name of a Greek mythological⁸（神话的） goddess of fate, "who spins the thread of life." People who have one copy of a variant, or form, of the KLOTHO gene, called KL-VS, tend to live longer and have lower chances of suffering a stroke whereas people who have two copies may live shorter lives and have a higher risk of stroke. In this study, the investigators⁹ found that people who had one copy of the KL-VS variant performed better on a battery of cognitive¹⁰ tests than subjects who did not have it, regardless of age, sex or the presence of the apolipoprotein（载脂蛋白） 4 gene, the main genetic risk factor for Alzheimer's disease.

 

"This study shows the importance of genes¹¹ that regulate the multiple aging processes involved in the maintenance of cognitive function," said Suzana Petanceska, Ph.D., program director in NIA's Division of Neuroscience. "Understanding the factors that control the levels and activity of KLOTHO across multiple organ systems may open new therapeutic¹² avenues for prevention of age-related cognitive decline and dementia."

 

The investigators tested a variety of cognitive skills, including learning, memory, and attention. More than 700 subjects, 52 to 85 years old were tested as part of three studies. None had any sign of dementia. Consistent with previous studies, 20 to 25 percent of the subjects had one copy of the KL-VS variant and performed better on the tests than those who had no copies. Performance on the tests decreased with age regardless of whether a subject had one or no copies of the KL-VS gene variant.

 

The KLOTHO gene provides the blueprint¹³ for a protein made primarily by the cells of the kidney, placenta（胎盘）, small intestine¹⁴（肠）, and prostate（前列腺）. A shortened version of the protein can circulate through the blood system. Blood tests showed that subjects who had one copy of the KL-VS variant also had higher levels of circulating klotho protein. The levels decreased with age as others have observed. The researchers speculate that the age-related decrease in circulating levels of klotho protein may have caused some of the decline in performance on the cognitive tests.

 

"These surprising results pave a promising¹⁵ new avenue of research," said Roderick Corriveau, Ph.D., 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."

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