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'Long life' gene might also protect against mental decline

02 February 2015

By Dr Victoria Burchell

Appeared in BioNews 788

A genetic variant may not only help some people live longer, but also changes the way their brain ages, a study suggests.

About one fifth of the population carries a single copy of a variant called KL-VS, which has been associated with an increased lifespan, improved heart and kidney function, and mental acuity.

In a report published in the Annals of Clinical and Translational Neurology, researchers scanned the brains of 422 healthy adults aged 53 years and over and found that a part of the forebrain was ten percent larger in people carrying one copy of the variant than in those without, regardless of age.

'The thing that is most exciting about this is that this is one of the first genetic variants we've identified that helps promote healthy brain ageing,' Dr Jennifer Yokoyama, assistant professor of neurology at the University of California, San Francisco (UCSF) and first author of the study, told CBS News.

The affected brain region - the right dorsolateral prefrontal cortex (rDLPFC) - is important for planning and decision-making. This part of the brain shrinks during normal ageing, which the researchers say may be one reason why older people can be easily distracted and have difficulty juggling tasks. Their findings suggest that the rDLPFC still shrinks with age in people who carry the variant but the brain region appears to be larger to begin with than in those without the variant.

The researchers also asked the participants to perform a series of mental tasks designed to test the functions controlled by the rDLPFC; those with one copy of the variant significantly outperformed those without.

'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,' senior author Dr Dena Dubal, assistant professor of neurology UCSF, told The Guardian.

The KL-VS variant increases expression of the protein klotho, which is produced in the kidney and brain but has functions throughout the body. The authors suggest that increasing klotho may also improve other aspects of brain function such as connectivity between neurons, an idea which is supported by previous mouse studies.

They are now interested to understand how the brain alterations in people with the KL-VS variant can affect diseases like Alzheimer's disease.

'The brain region enhanced by genetic variation in klotho is vulnerable in aging and several psychiatric and neurologic diseases,' said Dr Yokoyama. 'It will be important to determine whether the structural boost associated with carrying one copy of KL-VS can offset the cognitive deficits caused by disease.'

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