9th May 2014

Single gene boosts IQ by six points

A variant of the gene KLOTHO is known for its anti-aging effects in people fortunate enough to carry a copy. Now researchers have found that it also has benefits when it comes to brain function.

A team led by the Gladstone Institutes and UC San Francisco has discovered that a common form of KLOTHO – a gene already associated with long life – also improves learning and memory. This finding could lead to new treatments for age-related diseases like Alzheimer’s.

A variant of this gene is KL-VS, which appears to increase overall levels of KLOTHO in the bloodstream and brain. The researchers found that people who carry a single copy of the variant – roughly one-fifth of the population – perform better on a wide variety of cognitive tests, equivalent to a six point higher IQ. A total of 718 adults between ages 52-85 were tested for memory, attention, visuo-spatial awareness and language. Based on the results, variation in the KL gene may account for as much as 3% of variation in IQ of the general population. For comparison, the previous record-holding genes – HMGA2 and NPTN – each account for just 0.5%. KL-VS could therefore be the most important genetic agent of non-pathological variation in intelligence ever discovered.

When the researchers modelled the effects in mice, they found it strengthened the connections between neurons that make learning possible (what is known as synaptic plasticity), boosting the action of cell receptors vital to forming memories. Mice with elevated KLOTHO performed twice as well as controls in some cognitive tests – such as remembering where a hidden platform was located in a water maze.

Surprisingly, the effects of KLOTHO were evident in mice young and old. They didn't correlate with age in humans, either. In other words, KLOTHO works in a manner independent of aging and seems to boost cognitive reserve at different life stages. The researchers state that in healthy, aging humans, positive cognitive effects of carrying the KLOTHO variant may even exceed the harmful effect of carrying the notorious ε4 variant of the APOE gene – known for its contributions to Alzheimer's. Since elevated levels of KLOTHO appear to improve cognition throughout the lifespan, raising its level could build cognitive reserve as a buffer against the disease.

"Because cognition is a highly valued aspect of brain function that diminishes with aging and disease, the potential to enhance it even slightly is of great potential relevance to the human condition," said Dena Dubal, PhD, assistant professor of neurology and lead author of the study. "As the world's population ages, cognitive frailty is our biggest biomedical challenge. If we can understand how to enhance brain function, it would have a huge impact on people's lives."

The research was published yesterday in Cell Reports.

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