Source: Washington Post
Date: 26 December 2006

Longevity Gene Also Keeps the Mind Sharp

By Ed Edelson
HealthDay Reporter

TUESDAY, Dec. 26 (HealthDay News) -- A gene variant that's associated with long life also seems to contribute to enhanced mental function to the century mark and beyond, a new study found.

"In the last few years, we have identified several longevity genes that allow people to get to the age of 100," said study lead author Dr. Nir Barzilai, director of the Institute for Aging Research at Albert Einstein College of Medicine in New York City. "We have found one longevity gene that distinguishes those with good or bad mental function."

The study included 158 people of Ashkenazi (Eastern European) Jewish descent who were 95 or older. The gene variant, designated CETP VV, produces a protein that increases the size of the lipoprotein particles that carry both "good" HDL cholesterol and "bad" LDL cholesterol in the blood. It also increases HDL levels, the researchers said.

Researchers believe that larger cholesterol particles are less likely to lodge themselves in blood vessels. So, people with the CETP VV gene seem to have a lower risk of heart attack and stroke, which may explain their unusual longevity. "It is generally thought that a larger lipoprotein size is more protective of the cardiovascular system," Barzilai said.

That protective effect may operate in the brain, keeping arteries open to help preserve mental function, he said, but there might be another protective mechanism that is yet to be discovered.

Previous studies by the Einstein group have shown that centenarians are three times more likely to have the CETP VV variant than the general population. The research assessed its effect on the mental function of the study participants who were administered a standard test. Those with the CETP VV variant were twice as likely to have good brain function as those lacking the variant.

That finding was validated in a study of 124 persons ages 75 to 85 enrolled in a different trial, the Einstein Aging Study. Those who did not develop dementia were five times more likely to have the favorable gene variant than those who did.

The findings are published in the Dec. 26 issue of the journal Neurology.

There is a possible practical application to the finding, said Dr. Richard Lipton, director of the Einstein Aging Study. Until now, he said, the best advice that could be given to people who wanted to live a century or more was "choose your parents carefully."

"But now that we know the biochemistry that goes with this gene, high HDL levels and large lipoproteins, we could develop drugs that have the same profile as this gene," Lipton said.

One major effort to develop such a drug has just ended in failure, with Pfizer Inc. terminating studies of an HDL-raising medication, torcetrapib, because of an increased death rate in people taking the drug.

But several other companies are working on other HDL drugs, Lipton said. "The hope would be that these agents, which are being developed primarily to prevent heart disease, could also successfully promote cognitive aging," he said.

It isn't clear yet whether all the HDL-boosting medications being tested will have the same failing as torcetrapib, Barzilai said.





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