Centenarian advantage: some old folks make cholesterol in big way.

Healthy living undoubtedly plays a role in longevity. But studies have shown that siblings of centenarians are 8 to 17 times as likely as the average person to see 100. That link suggests that a potent benefit runs in the family's genes.

Researchers now offer an explanation for a portion of this hereditary good fortune. In the Oct. 15 Journal of the American Medical Association, physician Nir Barzilai of the Albert Einstein College of Medicine in New York and his colleagues report that Jewish near-centenarians and their offspring are more likely than other people to have large cholesterol particles in their blood, a condition conducive to good health. What's more, the old people and their children are more likely than others to carry a variant form of a gene called CETP. This gene encodes the cholestryl ester tranferase protein (CETP), which plays a role in the formation and movement of cholesterol particles in the body.

The researchers enlisted Jews of eastern European descent because the group has a history of longevity and its members tend to marry within the population, creating a genetically homogeneous group.

For the cholesterol investigation, Barzilai's team obtained blood samples from 213 Jewish men and women, average age 98, all of whom had been living independently at age 95. Half were centenarians, and ages ranged from 95 to 107. The researchers also got blood samples from 216 of the group's offspring. For comparison purposes, the scientists obtained blood from 258 other Jews, some of whom were spouses of the offspring. Also, the researchers had blood samples from 589 white, unrelated, non-Jewish people. The average ages in the offspring and comparison groups ranged from 68 to 70 years.

Doctors currently measure blood concentrations of two forms of cholesterol, high-density and low-density lipoprotein (HDL and LDL), to assess risk of heart disease. In the new study, the very old people and their offspring were significantly more likely to have large versions of both HDL and LDL than were people in either control group. The size correlation was independent of the concentrations of HDL and LDL.

Scientists theorize that small LDL particles penetrate vessel walls more easily than large particles do. This heightens the risk of atherosclerotic plaques, Barzilai says.

In Barzilai's recent work, genetic tests revealed that the very old participants and their offspring were three times as likely as the Jewish control group to have a specific variation in their CETP gene. Members of the non-Jewish control group weren't tested for this variation.

When the researchers considered the health of members of the offspring and spousal groups, they found that those who showed high blood pressure and heart problems were less likely to have large cholesterol-particles than their healthier counterparts were.

"These findings are striking," says David B. Finkelstein, a molecular biologist at the National Institute on Aging in Bethesda, Md. The work strongly suggests that cholesterol-particle size correlates with health risk, he says. "If I were a drug company reading this, I'd want to [find agents that] modify particle size," he says.

Indeed, the drug company Pfizer, based in New York, is currently testing a CETP inhibitor as a promoter of heart health.

Finkelstein points out that there could be other variant forms of CETP--or of other genes--that influence the size of cholesterol particles.

Also, Barzilai notes, genetic variations that appear to impart benefits to a Jewish population might not occur in other ethnic groups.