Cholesterol-linked gene may be key to long life

Study of Ashkenazi Jews shows jumbo-size proteins help avoid some illnesses

October 15, 2003|By Jonathan Bor | Jonathan Bor,SUN STAFF

Milton Garfunkel has no idea why he has lived to be 99, but finds it curious that his elder sister died at 102 and two brothers lived until they were 92 and 90. All he knows is that aside from bad knees that he blames on many years of handball, he feels fabulous.

"I think I can be 120, the way I feel," says Garfunkel, a retired salesman who lives independently with his wife, Peggy, in Yonkers, N.Y. Peggy is 95 and isn't concerned about why she's lived so long.

"Why?" she asks rhetorically. "Why not?"

Researchers aren't sure they've found the secret to the Garfunkels' longevity, but today they're reporting that they've found a genetic variation that may protect people such as the Garfunkels from many afflictions that kill most humans long before the century mark.

The variation, they say, produces lipoproteins - the particles that carry good and bad cholesterol through the bloodstream - that are extremely large. Their bulk could keep them from sticking to the walls of arteries and causing blockages, the culprit behind heart disease, stroke and various types of dementia.

The findings, reported in today's Journal of the American Medical Association, came from a study of 213 Ashkenazi Jews, including the Garfunkels. It was conducted by scientists from the Albert Einstein College of Medicine in the Bronx and the University of Maryland School of Medicine in Baltimore.

To qualify, volunteers had to be at least 95 years old, although 45 percent were at least 100 and at least one participant clocked in at 107.

Dr. Nir Barzilai, an Albert Einstein molecular biologist who directed the study, said the Ashkenazis weren't chosen because Eastern European Jews tend to live longer. Instead, scientists picked them for their genetic similarity, which stems from early geographic isolation and a long reluctance to intermarry. This makes it easier to conduct genetic studies.

So-called "founder groups," such as Ashkenazi Jews and the Amish of Pennsylvania, have been the focus of many scientific studies in recent years. Although much of that research has focused on genes that cause disease, scientists in the longevity study wanted to find genes that keep people alive.

Though many Americans focus on diet and exercise as keys to longevity, Barzilai said, few of the centenarians - a term he uses loosely to describe his subjects - are health nuts.

"No one ate yogurt all their lives, none were vegetarians," said Barzilai. And while many followed sensible diets and exercised, others smoked and ate lots of cholesterol-rich meats.

At the same time, many had parents and siblings who lived past 100. This made it likely that the oldsters shared gene mutations that protected them against some common causes of death - heart disease, stroke, diabetes, Alzheimer's and cancer.

Though Barzilai doesn't endorse smoking, he noted that the cholesterol mutation exerted such a powerful protective effect that many of his volunteers never developed lung disease despite decades of puffing cigarettes and cigars.

Among his volunteers was a 95-year-old woman who had smoked since she was 8 and who - not coincidentally- has a 100-year-old sister and a brother who's 97.

In the United States, where the average life span is 76.9 years, the chance of living to 100 is 1 in 100,000. The chance of reaching 95 is 1 in 50,000.

In their search for the key to their subjects' longevity, scientists took medical and family histories, along with blood samples. For comparison, scientists conducted the same tests on subjects with more typical genetic profiles.

Among the Jewish volunteers, what stood out was a gene variation that caused particles of lipoproteins to be exceptionally large. The variation was found in nearly half the volunteers, turning up four times as frequently as it did in control groups. Scientists found the same jumbo-sized proteins in the subjects' children.

"The gene effect is quite huge, but it doesn't explain all of them," said Barzilai, noting that slightly more than half of the elderly Jews did not have the gene. It's likely that other genes contributing to longevity will show up in future studies.

Dr. Alan Shuldiner, a geneticist at the University of Maryland Medical Center, noted that large particles of lipoprotein seem to slow aging even if the subject's LDL ("bad cholesterol") level is high. This doesn't mean people shouldn't try to reduce LDL levels, he said - just that a lucky few are protected.

People who want to know if they're blessed with large lipoproteins can pay for a blood test known as a lipid profile, which must be ordered by a doctor.

But someday, particle size may be more than a matter of curiosity. An experimental drug designed to protect diabetics from heart complications works by increasing lipoprotein size. Someday, the researchers said, doctors may be able to offer similar drugs to extend life spans.

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