Centenarians' Inner Secrets Are Slowly Revealed

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Centenarians' Inner Secrets Are Slowly Revealed

By Claudia Dreifus, The New York Times

February 24, 2004

Dr. Nir Barzilai often feels misunderstood.

"People think I'm searching for the Fountain of Youth," he said over coffee. "I'm not. I'm looking for ways to make old age better."

Toward that goal, Dr. Barzilai, the director of the Institute for Aging Research at the Albert Einstein College of Medicine in the Bronx, has spent five years investigating the genes and habits of 300 Ashkenazi Jews who have lived to be an average of 100.

His study has provided important information about longevity, including confirmation that picking the right parents is crucial for living a long life.
Almost all his research subjects had ancestors who were long-lived.

Dr. Barzilai, who was born in Israel 48 years ago, describes his own genetic endowments as good for medicine, but mediocre for longevity. His father, David, 80, was dean of an Israeli medical school, but has had bypass surgery. Dr. Barzilai's mother, Drora, 71, has diabetes.

What is needed, he said, are "environmental interventions to give them, and perhaps myself, a long life."

"I hope to do it." he said.

Q. How did this idea of yours, to look for clues about longevity in the genes of people who have lived to be 100, first develop?

A. I had been doing diabetes research. I still do. Diabetes is a disease that ages its victims rapidly. I'd been trying to understand how certain nutrients such as high sugar levels translate into biological actions in rats. We know that rodents live significantly longer when their calories are restricted.
When you do any work in this area, the question of heredity versus environment comes up. A researcher can't help but ask why some people's health is more affected by a certain diet than others? This led me to thinking about the heredity part of longevity.

I wondered why people born at the beginning of the last century who are still alive are relatively healthy. I wondered what they had in their genes that was special. When they were born, the average life expectancy was 40. What made it possible for them to live more than twice the average? These days, so many scientists look for the genes for specific diseases. I wanted to go the opposite way, look for genes that helped people live healthier and longer lives.

Q. Your study group consisted of about 300 Jews of Eastern European origin, ages 95 to 108. Why did you pick them?

A. It's very important to study a homogeneous population. The genetic makeup of Ashkenazi Jews is more homogeneous than many other groups'. Most are descended from people who had some very unfortunate experiences with history. In the 17th century, a series of pogroms and plagues decimated the Jews of Eastern Europe.

Their numbers were reduced to perhaps around 30,000. So the "founder group" is not very diverse genetically. This is why studying the Ashkenazi Jews was so useful in finding the breast cancer gene. It's why they are being used today to study the genetics of ovarian cancer.

Locating the 100-year-olds didn't take much. There were articles about what we were doing in the newspapers. We went to old age homes in the U.S. Often, people came to us by word of mouth.

Q. Did you consider doing your study in the Central Asian Georgia, the reputed homeland of the yogurt-eating-apricot-munching long-lived?

A. No. We think that claim may be inaccurate. There may be a history of people there exaggerating their longevity because Stalin, who was Georgian, wanted it known that Georgians were long-lived. Under Communism, people were exaggerating their age, bringing in their grandparents' identity cards when dealing with officials.

Q. How exactly did you conduct your study?

A. Using a mixture of medical science and anthropology, we arranged mini-family reunions with the centenarians and their 70- and 80-year-old "kids," about half of whom had inherited the genetic mutation we were looking for. The spouses of these "kids" were our control group. They had shared an environment with someone with longevity genes, though they were unlikely to have them themselves.

At these reunions, we took extensive medical and family histories. The centenarians usually had a better memory than their children. We measured body fat and weight. A low percentage, we think, is one marker for longevity.

Q. Are you looking for the genetic markers for longevity?

A. Yes, and we've found several so far. The most important thing we've found is that most centenarians have a lot more than average H.D.L. proteins, the good cholesterol, in their blood. Also, they had a lot more of them when they were younger, because their children have a lot more than their peers do. Also, size matters with the protein molecules. Eighty percent of the children of the centenarians had larger than average high density lipoproteins.

Q. What do your findings linking H.D.L. cholesterol and aging mean genetically?

A. This led us to look at candidate genes involved in the regulation of lipid metabolism, and it means we've found a gene that is important in longevity. This gene obviously has a purpose. But if it's partially deactivated, it will cause you to live longer. If you have this genetic characteristic, your chance of getting from age 70 to 100 increases by over threefold. Among the 70-year-old control group we studied, 8 percent have this mutation. Among the 100-year-olds, 25 to 30 percent of them have it. We will have to look at other parts of this gene to see if there are more mutations. There are other genes that also control H.D.L. and the sizes of lipoproteins, and we're looking for them.

The gene that we discovered only explains 18 percent of the longevity. But it is possible that if everyone has the effect of this gene they will get to be 100. We want to explain 100 percent of the reasons for exceptional longevity. So we are looking at other genes. A very few of the oldest people we've studied actually do not have large lipoproteins and do not have any mutations that we've discovered so far.

These few often don't wear glasses and they don't use hearing aids. The genes for that group may be the most important to be found. We're looking for them right now.

Q. How do your findings change how medicine will deal with aging?

A. They point to the possibility of a drug. There are several companies that are developing a drug to act on the gene I've found and that is associated with longevity in my study. One is right now in Phase 3 trial, and it looks like it will increase H.D.L. and the size of the protein.

Q. Can you give us some general findings about the 100-year-olds you studied?

A. They were often healthier than the spouses of their 70-year-old kids. They often got the same diseases that their sons and daughters-in-law got, but 30 years later.

And they were, for the most part, unless they had diabetes, fairly healthy right up until the end. Even when they had serious diseases, the progress was slower. The medical billings for centenarians in the last two years of their lives was, on the average, $8,000. For people who died between 60 and 70, it was $24,000.

The most common thing this group had is that they did not reveal any particular lifestyle secret for their own longevity. When asked specifically, none has exercised. None was a vegetarian. Not a single one ate yogurt throughout his life.

In fact, 30 percent were overweight. Some smoked. The fact that they had a strong family history of exceptional longevity seemed to be the main commonality. This supports the notion that they have special genes protecting them from their environment.

One of the things I'm worried about is that my study will encourage people not to engage in healthy environmental practices such as diet and exercise, because they'll think it doesn't matter.

Q. A personal question, what does your own lipid profile look like?

A. That's one area where I most certainly do have a stake in this drug that's coming. I have a good H.D.L. count, but unfortunately, my molecules are small. This worries me. I'd like to be a healthy centenarian. And I will probably take this drug when it is ready.