Single Gene Could Lead to Long Life, Better Mental Function

A variation of a gene that controls the size of cholesterol molecules in the bloodstream is common among elderly Ashkenazim who remain mentally sharp

by Charles Q. Choi

Older man at work

If you live to 100, as roughly one in every 10,000 people do, you will likely want both your mind and body intact. Researchers have now discovered a gene that accomplishes just that, apparently protecting the brain as well as prolonging life.

The Longevity Genes Project, initiated by Nir Barzilai, director of the Institute for Aging Research at Albert Einstein College of Medicine, investigates people who live exceptionally long lives.

"There's a strong family history of longevity in these people," says Barzilai. "Research has shown the odds of having exceptional longevity are about 10 to 18 times more if you have a centenarian in your family. And these usually aren't vegetarians or professional athletes. Some have smoked for 90 years."

Barzilai and his colleagues examined 158 people of Ashkenazi, or Eastern European Jewish, descent who were 95 years of age or older. They chose Ashkenazi Jews since current generations stem from a relatively limited number of ancestors. This means they have a comparatively uniform genetic makeup, making it easier to identify important genetic differences.

The scientists gave these volunteers a common test of mental function, consisting of 30 questions. Correctly answering 25 of the questions meant a subject passed the test. Those centenarians who passed were two to three times more likely to have a common variant of a particular gene, called the CETP gene, than those who did not. When the researchers studied another 124 Ashkenazi Jews between 75 and 85 years of age, those subjects who passed the test of mental function were five times more likely to have this gene variant than their counterparts.

The CETP gene variant makes cholesterol particles in the blood larger than normal. The researchers suggest smaller particles can more readily lodge in the lining of blood vessels, leading to fatty buildups, which are a risk factor for heart attacks and strokes.

Whether or not this gene variant protects the brain by preventing this buildup, or through some other mechanism, remains uncertain, says Barzilai. Future research should also investigate whether this gene has an effect on dementia associated with Alzheimer's disease, says pathologist and human geneticist George Martin at the University of Washington.

Pharmaceutical companies are currently developing drugs that mimic the effect of this gene variant, says Barzilai. Unfortunately, one known as torcetrapib, manufactured by Pfizer, was pulled in December due to increased death and heart problems among study subjects, "but others in development aren't seeing that, so it might just have been a problem with that drug," says Barzilai. "If not, it's a question people might face--whether or not people want to prevent Alzheimer's even if there's a small risk of getting a heart attack."

Barzilai and his colleagues reported their findings in the December 26 Neurology.

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