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Dr. Thomas T. Perls leaned in close and spoke gently, locking his eyes into Mary Lavigne's. He had pulled his chair to within two feet of the petite, white-haired woman in her sunny living room in Lancaster, Mass.

"When were you born?" he asked, amplifying his voice. "What's your birthday?"

Miss Lavigne pulled back an inch. Unlike the other two women Dr. Perls had interviewed earlier in the day, she can hear just fine.

"Sept. 28, 1899," she said.

"You've been in three centuries!" Dr. Perls said. "It's amazing. Do you think it's amazing?"

"Yeah, I'm thankful. I'm very thankful that I'm able to take care of myself," Miss Lavigne (pronounced luh-VEEN) said with her Massachusetts accent. She wore a beige and navy striped golf shirt, and she sat perfectly straight, her delicate hands folded on her lap.

"Do you have great-great-grandchildren?" Dr. Perls asked.

"I never married," Miss Lavigne said with practiced determination. "I didn't want to get into it."

They spoke for several minutes about her early childhood in Quebec, her memory of the first automobiles and of hearing President William Howard Taft give a speech in Westbrook, Mass., in 1911. Then Dr. Perls, a geriatrician at Beth Israel Deaconess Medical Center, in Boston, and an assistant professor of medicine at Harvard Medical School, explained why he wanted to know so much about her. He wanted her to be part of his nationwide study of centenarians. If she agreed to participate, he would ask her to provide a DNA sample, to take a psychological test to measure her mental acuity (though it is obviously strong) and to consider donating her brain for research. Also, he would want to interview her closest living relatives.

"Who are the nephews or nieces most interested in your affairs?" Dr. Perls probed.

"Well, they're all interested in my affairs," she replied with a laugh. "They come to visit and they say: `I want this and I want that. I want this and I want that.' "

Like so many of the hundreds of centenarians Dr. Perls has interviewed in the last six years, Miss Lavigne left him and his associate, Dr. Margery Hutter Silver, a neuropsychologist who is also at Beth Israel and Harvard, shaking their heads over her clear thinking, her near-perfect health and her alert sense of humor.

"You don't realize it, because she doesn't act like it," Dr. Perls said, "but she is also legally blind."

Even Miss Lavigne's denunciation of marriage sounded familiar. About 14 percent of the women Dr. Perls has studied have stayed single for their 100 years. Could that be because unmarried women lead relatively unstressful lives? Maybe, Dr. Perls said. "Or maybe the fact that they are able to live independently means that they are able to manage stress better than the average person," he said.

In contrast, the centenarian men in the study group are all married, or have been. But there are more than five times as many women as men.

In nine years, Dr. Perls and his research staff have collected health data on some 1,500 centenarians. And the work has led him to a series of discoveries about the very old. They are healthier than anyone ever thought they were, first of all. They avoid the most devastating diseases of old age until the last few years of their lives. And almost all of them seem to be exceptionally good at managing stress and getting along with people.

Even those unmarried women are never alone. "They're full of good humor and gregarious," Dr. Perls said. "They're basically very happy, optimistic people. You look at a person like Mary Lavigne and you see she has people taking her to lunch, people looking after her, because she's so nice."

Most notably, Dr. Perls and his colleagues have recently found, centenarians seem to carry a small handful of genes that enable them to live to 100 or better.

In August, Dr. Perls and his colleagues — including two molecular geneticists, Dr. Louis M. Kunkel and Dr. Annibale A. Puca of Children's Hospital in Boston — announced the results of a study of centenarians with very old siblings. After examining their DNA, the researchers determined that a longevity-enabling gene might exist in a certain small stretch of chromosome No. 4, one of the 23 pairs of human chromosomes.

The researchers hope that Centagenetix, the Boston-based company they founded, will home in on that gene before next summer. Ultimately, the company hopes to identify a number of longevity genes, figure out how they work and create drugs that mimic their actions.

Dr. Perls does not think that genes alone keep people alive for so long. Most of his subjects have healthy life patterns. He has met some who live to a ripe old age even while smoking cigarettes or eating high-fat foods, but, he said, "These are the ones who you would suppose really have some spectacular genetic stuff going on."

Still, a great majority of his subjects never smoked. Few drink to excess. And though no particular diet seems to ensure long life, obesity is never part of the picture.

But Dr. Perls is adamant that good habits alone cannot get a person to the century mark. He said: "If you do absolutely everything right — you're Jack La Lanne, you've got the perfect diet, you're exercising for a really long time, you're happy-go- lucky and incredibly nice, and you're thin, I would say that without the appropriate genetic variations, it's still extremely difficult to get to 100."

The health histories of Dr. Perls's centenarians suggest that there are three kinds of people who achieve extreme old age. Forty percent are "survivors," those who live with chronic diseases for decades, beginning in their 60's and 70's. Another 40 percent are "delayers," who put off illness until their mid-80's. And the last 20 percent are "escapers" — people who avoid all age-related diseases until they are over 100.

Until very recently, centenarians were not numerous enough for study. Today, about 50,000 Americans are 100 or older, up from almost none at the turn of the previous century. By 2050, as many as 800,000 to one million Americans may still be alive at 100 or older, with improving health care practices.

Dr. Perls became fascinated by the extremely old when he was a geriatrics fellow at Harvard, taking his turn working at the Hebrew Rehabilitation Center for Aging in Boston. That was in the 1970's, and like other physicians at the time, he assumed that his centenarian patients would be the sickest. In fact, he had trouble finding them in their rooms. "One was playing the piano for everybody," Dr. Perls said. "Another one was a tailor, mending people's clothes."

In 1993, he began the New England Centenarian Study, which at first focused on eight Massachusetts towns. One of the first things that he and Dr. Silver found was that senility was not an inevitable accompaniment to old age. About 70 percent of the centenarian men, but only 30 percent of the women, were still clear-headed; the explanation is not known, but the researchers suspect women with dementia are more likely to survive than men with the condition.

Dr. Perls also found a surprising statistic about the centenarian women who were mothers. One in five of them had had at least one child after the age of 40. In the general population, only about 5 percent of mothers give birth that late.

"In other words, if you have a child after the age of 40, you have about a four and a half times greater than average chance of going on to 100," Dr. Perls said. "It isn't just the act of having a child, we don't think. But late motherhood is a marker." It shows that the entire body is aging slowly, he said.

The more centenarians Dr. Perls met over the years, the more obvious it seemed that longevity could be inherited. He often recalls the day he spotted a photograph in The Patriot Ledger in Quincy, Mass., of a man celebrating his 108th birthday with his 103-year-old sister.

The two of them turned out to have had four siblings who lived past 100, plus another sister, still living at 97. Among these siblings' first cousins were seven centenarians and 14 others who lived to be at least 90. Two other families among his subjects included similarly large collections of extremely old people.

Dr. Howard Fillit, director of the Institute for the Study of Aging, in New York, said the age of Dr. Perls's subjects had been the key to his discoveries. "It was Tom's great insight to recognize the value of studying families with large numbers of 100-year-old people," Dr. Fillit said.

By 1998, Dr. Perls had accumulated enough data to demonstrate that a person with a centenarian brother or sister was four and a half times as likely as the average person to live to be at least 91. This year, he has refined the statistics further: male siblings of centenarians have a chance 17 times as great as the average man's of living to 100. And female siblings are eight times as likely to reach 100.

On a walk through the Harvard Medical School campus four years ago, Dr. Perls described his centenarian families to Dr. Kunkel, the molecular geneticist. "We went back to my office and drew out the pedigree," Dr. Kunkel said. "To me, it was clearly genetic. I was pretty confident that if we looked for a gene, we would get something interesting."

Ultimately, Dr. Kunkel and Dr. Puca examined the chromosomes of 303 people in 137 families. At least one sibling in each family was 98 or older; the others were at least 90.

In those families, a stretch of DNA on Chromosome 4 stood out; another stretch, on Chromosome 2 was also a candidate, though not as strong. Now, Centagenetix will try to replicate the study with more subjects, and zero in on the gene or genes in those sites that may affect life span.

Dr. Perls says he will not be surprised if the gene they find somehow accomplishes the twin goals of slowing the aging process and protecting against disease.

One way such genes may operate, Dr. Perls said, is by limiting the activity of free radicals, which are unpaired electrons that cause corrosive damage to tissues throughout the body. Studies on laboratory creatures — mice, worms, yeast and fruit flies — have shown that certain genes can shield against free radical damage and prolong life span.

"We already know that free radical damage has an important pathogenic role in heart disease and stroke," Dr. Perls said, "and it may also play an important role in Alzheimer's disease. There's been pretty good research showing that it plays an important role in aging."

Though the gene study has clearly taken center stage, Dr. Perls's work with centenarians has raised many other questions that he hopes to investigate. For example, he said, he would like to study the theory that it may be possible for people to build a "cognitive reserve" that enables them to avoid dementia in old age. He described a 103-year-old man who, in psychological tests, showed no signs of senility. Yet after the man's death, when his brain was examined in autopsy, it was found to be laced with the tangles of dead cells that characterize Alzheimer's. Perhaps the man had been able to strengthen other parts of his brain — to build a cognitive reserve — to get around his disease.

Dr. Perls would also like to learn more about the psychology of longevity — how attributes like spirituality, optimism, humor, financial security, stress management and friendships help people live to be 100. "It would be very interesting to find out, no matter how good your genes are, what environmental things are a must," he said.

What are the chances that Dr. Perls himself, now 41, has some genetic propensity for longevity? It is a question he has definitely thought of. The good news is that his great- great-grandmother lived to 102. His mother is in excellent health at 78. Signs are even better for his wife, who gave birth to their youngest of three children when she was 41.

But whatever his genes have in store, Dr. Perls intends to do what he can to stretch their potential. In the past year, he has dropped 30 pounds from his 5-foot-11 frame, reaching a trim 170, by taking up spinning classes and coaching his 9-year-old's soccer team.

The way to lengthen your life, Dr. Perls pointed out, is to add healthy years. "Even if we can't live to be centenarians," he said, "we can all be centenarianlike, in that we can try to compress the time that we're sick toward the very end of our lives."