Gene linked to long life also protects against mental decline in old age

Posted: January 27, 2015 at 5:40 pm

Sliced sections from two brains. On the left is a normal brain of a 70-year-old, whereas on the right is the brain of a 70-year-old with Alzheimers disease which is atrophied with a loss of cortex and white matter. Photograph: Jessica Wilson

People who carry a mutated gene linked to longer lifespan have extra tissue in part of the brain that seems to protect them against mental decline in old age.

The finding has shed light on a biological pathway that researchers now hope to turn into a therapy that slows the progression of Alzheimers disease and other forms of dementia.

Brain scans of more than 400 healthy men and women aged 53 and over found that those who carried a single copy of a particular gene variant had a larger brain region that deals with planning and decision making.

Further tests on the group found that those with an enlarged right dorsolateral prefrontal cortex (rDLPFC), as the brain region is known, fared better on a series of mental tasks.

About one in five people inherits a single copy of the gene variant, or allele, known as KL-VS, which improves heart and kidney function, and on average adds about three years to human lifespan, according to Dena Dubal, a neurologist at University of California, San Francisco.

Her latest work suggests that the same genetic mutation has broader effects on the brain. While having a larger rDLPFC accounted for only 12% of the improvement in peoples mental test scores, Dubal suspects the gene alters the brain in other ways, perhaps by improving the connections that form between neurons.

To put our findings in perspective, we found that carrying one copy of the KL-VS allele confers a decade of resilience against the expected decline in structure and function of this important brain region, the dorsolateral prefrontal cortex, she said.

The genetic mutation leads to higher levels of a protein called klotho, which is made in the kidney and brain, but affects scores of biological processes in the body. In work published last year, the US team showed that boosting levels of klotho in mice made them smarter at memory and learning tasks, and they also lived longer.

The latest study, published in Annals of Clinical and Translational Neurology, suggests those who are lucky enough to inherit a single copy of the mutated gene may have some natural protection against brain diseases that often strike in old age. Though their brains still deteriorate with age, their mental faculties may decline more slowly because they have better functioning brains to begin with.

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Gene linked to long life also protects against mental decline in old age

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