A gene variant that scientists already knew to be associated with longer life also seems to make people smarter, and may help offset the effects of normal cognitive decline in old age, according to a team of San Francisco researchers.
The findings, published in the journal Cell Reports, are good news for the roughly 1 in 5 people who have the genetic trait, which is a variant of the klotho gene. Beyond that, scientists hope the findings will help them develop tools for retaining, or even boosting, intelligence in people who have suffered cognitive losses, either from disease or through the normal course of aging.
“What we’ve discovered is a cognitive enhancer,” said Dr. Dena Dubal, an assistant professor of neurology at UCSF and lead author of the study, which was done with researchers from the Gladstone Institutes. “This may represent a new way to treat problems of cognition in the brain.”
She spins the thread of life
The name of the gene comes from Greek mythology — Klotho is one of the three sisters of fate, and she spins the thread of life. The gene is responsible for secretions of the hormone klotho, which is thought to have effects on a variety of biological systems and has been shown to disrupt some processes associated with aging.
Having a single copy of the gene variant, called KL-VS, appears to increase the amount of klotho that circulates in the blood. Studies from the late 1990s, when the gene variant was discovered, found that people with the variant tend to live about five years longer than others, and in animals, the effect is even more profound.
Cognitive loss — not necessarily dementia, but simple forgetfulness or slower thinking, for example — is almost universal among older people.
People with the variant still experienced cognitive loss as they got older, but klotho seems to have pumped up their intelligence over a lifetime, giving them a greater cognitive reserve to draw from later in life, making their losses less pronounced.
Starting at ‘a higher level’
“Klotho increases cognition but doesn’t replace aging-related decline,” said Dr. Lennart Mucke, director of neurological research at Gladstone. “You’re just coming down from a higher level.”
In a study of more than 700 people ages 52 to 85, the scientists found that those with the gene variant performed better on cognitive tests than those without it. Perhaps more exciting, scientists said, was another finding from the same study: that older, cognitively impaired mice performed better on tests of their brain power after they were engineered to produce more of the klotho hormone.
That suggests that there’s hope for repairing damage done to an aging brain that already is showing signs of normal cognitive decline, scientists said. “We are discarding right and left our old notions of the older brain and its capabilities,” said Dr. Molly Wagster, chief of the behavioral and systems neuroscience branch of the National Institute on Aging. “The more that we learn about the brain’s capabilities, the more we can target prevention and interventions.”
Dubal and Mucke believe that klotho improves cognition by helping strengthen the communication lines between brain cells. They were able to show, in mice, that high levels of klotho in brain tissue were associated with high levels of GluN2B, a protein that helps build synapses.