Longevity Gene Keeps Brain Agile

People with a cholesterol gene variant are more likely to live longer and with better brain function.

A genetic variation that helps people live longer may also help keep their minds intact as they age. A study of a group of elderly people of Ashkenazi Jewish descent found that those with the genetic variation, which changes the way the body processes cholesterol, perform better on tests of mental ability.

By studying people who age well, like this 102-year-old man, researchers are uncovering the genetics behind healthy aging. Credit: Longevity Genes Project

Nir Barzilai, study author and head of the Longevity Genes Project at Albert Einstein College of Medicine, in New York, previously showed that the same genetic variation was more common among Ashkenazi Jews who live to be 95 or older. After uncovering this and other genes associated with longevity, the researchers examined whether the genes could explain why some people have sharper minds when they age. Barzilai says that studying cognitive ability in aging is important since most people want to reach old age but "they want to get there with their brain, and not just the body."

The researchers found that in a group of 158 people age 95 and older, those with the variant were twice as likely to pass tests of mental agility as those with a different version of the gene: 61 percent of those with the protective variant had good cognitive function, compared with 30 percent of controls. The researchers also confirmed these findings using a younger group of Ashkenazi Jews in the Einstein Aging Study, also based at Albert Einstein College of Medicine. Among 124 people ages 75 to 85, those with the gene variant were five times more likely to be protected from dementia and perform well in memory tests. Ashkenazi Jews--Jews of Eastern-European descent--are a tight-knit group with a relatively uniform genetic makeup, making it easier for researchers to identify important differences among them.

The genetic variation causes people to produce less of a protein called cholesterol ester transfer protein (CETP). Barzilai says that CETP has two functions: it helps move cholesterol from the arteries to the liver, and it helps control the size of cholesterol particles circulating in the blood. People with the protective gene variant have higher levels of "good" HDL cholesterol and also produce bigger cholesterol particles, which scientists believe may not stick to blood-vessel walls as easily as small particles do.

It's not yet clear how CETP affects the brain. But Benjamin Wolozin, a scientist at Boston University Medical Center who studies the role of cholesterol in Alzheimer's disease, says, "It's easy to imagine that changes in CETP could affect cognitive function." Cholesterol is an important component of brain cells, Wolozin says, and cholesterol levels in the blood also affect the health of blood vessels that supply the brain with oxygen.