Cracking the Code of Longevity

Living for 100 years is an unlikely prospect for most of us. But for those lucky few who make it to the century mark, a crucial gene variation relating to cholesterol levels may play an important part in their longevity.

Researchers now believe that this gene variation could also protect against age-related memory loss and senility -- keeping seniors sharp well into their 80s and 90s. The findings reported in this week's issue of the journal Neurology say future drugs may eventually help to provide others with this protection.

"We looked for reasons of longevity among the study group," said study author Dr. Nir Barzilai, director of the Institute for Aging Research at Albert Einstein College of Medicine. "We realized that maybe it's genetic because their habits varied widely."

The study looked at 158 people of Ashkenazi, or Eastern European Jewish descent, who were 95 years old or older.

Barzilai and his fellow researchers found that a quarter of those who lived to an average age of 100 had a certain genetic variation that increased the size of "good" HDL cholesterol particles in their blood.

This variation was present in only about one out of 12 subjects who were 30 years younger, suggesting that having the gene was associated with a better chance of a longer life.

"The idea that treating the standard cardiovascular risk factors (high cholesterol, low HDL, high blood pressure, diabetes) could forestall cognitive decline is provocative," said Dr. Dan Rader, director of preventive cardiology at the University of Pennsylvania School of Medicine. "Specifically, if HDL is really protective against dementia, it strongly supports the idea of developing treatments targeted toward HDL."

Researchers also found those who had the gene variant were twice as likely to score well on a brain function test as those without it. Similar results were found in a group of 124 Ashkenazi Jews between the ages of 75 and 85.

Experts not involved with the study say the findings are significant.

"Among long-lived individuals, this genetic variant also seems to preserve cognitive performance by a mechanism that seems independent of cardiovascular health," said Dr. David Beversdorf of the division of cognitive neurology at Ohio State University. "This is, to my knowledge -- and to the authors' knowledge -- the first gene identified with any of these effects."

But exactly how this change in HDL may preserve brain function in old age is less clear.

"It can work in a number of ways. It raises good cholesterol and increases lipoprotein particle size, which seems to prevent particle buildup in the arteries," Barzilai said. "Several things are possible."

HDL and the Aging Brain

Usually, discussions of the interplay between "good" HDL cholesterol and "bad" LDL cholesterol are limited to heart health and the artery-hardening disease atherosclerosis. However, these new findings suggest a link between senility and high cholesterol problems.

Dr. John Messmer, associate professor in the department of family and community medicine at the Pennylvania State College of Medicine, said he has thought for a "long time" that much of what is found in dementia is associated with atherosclerosis.

"Many researchers in the cardiovascular field suspect that much cognitive decline and even dementia may be due to atherosclerosis of cerebral vessels, and high HDL is one of the strongest protective factors against atherosclerosis known," Rader said.

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