People who carry a certain variant of the longevity gene tend to have larger volumes in the part of the brain linked to planning and decision-making.
The findings support past data that show older adults who possess a KLOTHO allele, called KL-VS, tend to perform higher on cognitive tests, the University of California-San Francisco reported. The recent findings showed KL-VS strengthened the connections between neurons and improved learning and memory in mice.
About one in five people carry a single copy of KL-VS, which increases klotho levels, but about 3 percent carry two copies and tend to have a shorter lifespan. To make their findings, the researchers scanned the brains of 422 cognitively normal men and women aged 53 and older to determine their brain structures.
The researchers found the KLOTHO gene variant predicted the size of a region called the right dorsolateral prefrontal cortex (rDLPFC), which tends to deteriorate with age and could be responsible for sensitivity to distractions and trouble with multi-tasking.
They also found rDLPFC shrank with age in all three groups (those with one allele, two alleles or no alleles) but those with one copy of KL-VS had more volume in these regions. These brain volumes proved to predict how well the participants did on cognitive tests.
"We've known for a long time that people lose cognitive abilities as they age, but now we're beginning to understand that factors like klotho can give people a boost and confer resilience in aging," said senior author Dr. Dena Dubal, assistant professor of neurology at UCSF and the David A. Coulter Endowed Chair in Aging and Neurodegenerative Disease. "Genetic variation in KLOTHO could help us predict brain health and find ways to protect people from the devastating diseases that happen to us as we grow old, like Alzheimer's and other dementias."
A statistical test showed larger rDLPFC volumes seen in single copy KL-VS carriers was responsible for about 12 percent of the effect of the variant on cognitive abilities. Despite these findings, the researchers noted the allele could have other effects on the brain such as "increasing levels or changing the actions of the klotho protein to enhance synaptic plasticity," or changing connections between neurons. In a past experiment, researchers determined raising klotho in mice increased the activity of a cell receptor that is key in the storage of memories.
"The brain region enhanced by genetic variation in KLOTHO is vulnerable in aging and several psychiatric and neurologic diseases including schizophrenia, depression, substance abuse, and frontotemporal dementia," said Jennifer Yokoyama, first author and assistant professor of neurology at UCSF. "In this case, bigger size means better function. 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."
The findings were published in a recent edition of the journal Annals of Clinical and Translational Neurology.
