Unlocking the secrets to a long life

By Carol M. Ostrom
Seattle Times staff reporter

	KEN LAMBERT / THE SEATTLE TIMES Eva Fridell of Sequim turned 110 in May. Her relatives believe a feisty spirit and good sense of humor helped contribute to her long life.
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How did Eva Fridell get to be 110?

More precisely: How did Eva Fridell get to be 110 and still able to chortle at a subtle joke? Without losing her thick hair? With so little change in her heart that this year's EKG looked like a photocopy of one taken 20 years ago?

Fridell, who lives in Sequim, never dieted. She never gulped handfuls of antioxidants. Perhaps there's a clue in a sparkly bottle of Crown Royal whiskey, sent by admirers who learned of her fondness for happy hour. "That's good stuff!" she says with a twinkle.

On the other hand, her long life could be linked to her feisty spirit. Or her wispy 74-pound, 4-foot-11-inch frame.

In the search for the secrets to longevity, the very old provide some of the most important clues. Mice, worms, flies and yeast have done their part, too, as scientists gain ground in an age-old quest.

For more information "Beyond Therapy: Biotechnology and the Pursuit of Happiness," President's Council on Bioethics: www.bioethics.gov/reports/ beyondtherapy/index.html Quiz: Test your expected longevity

Powerful new tools of genetics and molecular biology have accelerated discoveries, leading not only anti-aging pundits but serious scientists to predict our life span will soon increase substantially.

In the past century alone, we've gone from an average life span of 47 to about 77. In 2000, the census counted 31 people 110 and over in Washington state alone. Today, the documented outer edge of human longevity is Jeanne Calment, a Frenchwoman who died in 1997 at age 122 and five months.

That sort of life span threatens to turn a boomerism into a reality: Maybe 55 or 60 really is just the beginning of middle age, and maybe it stretches to 70 or 75. "Sixty is the new Thirty," proclaims the latest cover of AARP Magazine, featuring the young-forever face of supermodel Lauren Hutton, about to turn 60.

Scientists, not surprisingly, disagree about the limits to longevity. Some on the outside edge believe a life span of 4,000 or 5,000 years might be within reach of people alive today. Others insist there is no such thing as "anti-aging" science.

	JOHN LOK / THE SEATTLE TIMES Steven Austad, a longevity researcher, holds a wild house mouse in his laboratory at the University of Idaho in Moscow. Based on his studies of the aging process in mice and other animals, Austad believes that by 2150 many humans will live to be 150 — but not all of his fellow researchers agree.

Medical ethicists and gerontologists worry that the pursuit of longevity — not to mention immortality — may reap societal chaos, perhaps even disrupting necessary cycles of life.

Meanwhile, more of us are achieving what scientists call "exceptional longevity." Realistically, how long can someone alive today expect to live?

Prominent longevity researchers Steven Austad and Jay Olshansky put money on it after Austad breezily predicted someone born in 2000 would live to 2150.

Austad, a biologist-turned-comparative-gerontologist at the University of Idaho, put down $150. Olshansky, an aging-demographics expert at the University of Illinois, Chicago, bet against him. "One hundred and fifty (years old) is absurd," Olshansky says.

Austad retorts that by 2150 there will many 150-year-olds. "I win this bet in a walk!"

By 2150, their $300 pot, now in a trust to which heirs will contribute, could grow to about $500 million.

By then, almost certainly, science and medicine will have made great progress.

Centenarians in Washington: The number of Washington residents age 100 or older who died in 2000: 254. The world's oldest living person (documented): A Japanese woman, Mitoyo Kawate, 114, is believed to be the oldest person alive by Guinness World Records. The previous record holder also was a Japanese woman. Kamato Hongo died recently at 116 on the island that also was home to the world's oldest man, Yukichi Chuganji, who died in September at 114. The world's longevity record (documented): Jeanne Calment, a French woman who died at age 122 and five months in 1997, is the current record holder. The family of an Albanian woman, Hava Rexha, says she was 123 when she died earlier this month, but her age has not been verified. The really old: What do they do that the rest of us don't? For the most part, people who live long, productive lives don't seem to realize they've done anything different. Most just do what comes naturally, but it seems to work, at least for them. Pick and choose your habits, because not all will work for everyone. But you may see a pattern, if you look closely. Eva Fridell of Sequim turned 110 in May. Her daughter says her mom rarely worried about things, often cautioning her to "just take one day at a time." A little slip of a woman, she doesn't diet and has always eaten whatever she wanted — but not a lot of it — said her daughter, Jean Saunders, 79. Jennie MacMahon of Beverly Hills, Calif., lived to three weeks before her 107th birthday. In her later years, she drank a small glass of sherry every afternoon at 3. She ate a lot of simple Asian food, though she was not Asian, and loved chocolates. Her exercise, she often said, was dealing the cards. And she was stress averse. She didn't go to funerals as a policy, even skipped her brother's funeral, relatives recalled, and refused to use certain words. "I don't say goodbye," she once explained. "I say, 'Until we meet again.' " Dr. Denham Harman, 87, of Lincoln, Neb., developed the "free-radical theory of aging" and still works an eight-hour day. He ran two miles a day until he was 82 and now walks regularly, keeps his weight down, has never smoked, takes antioxidants and nutritional supplements (C, E and selenium, among others) and — most important — stays busy. "If you don't stay busy, you die," says Harman, who recently traveled to England for a conference on aging.

But will those discoveries let us — even one of us — live to 150, much less 1,000? And even if they could, should we want to?

New definitions of 'very old'

On many points, Olshansky and Austad agree. They think the "oldest person" will become increasingly old. They think more of us will get to "very old." And they think much of the current so-called anti-aging movement — the one that sells immortality, along with costly products — is hucksterism, pure and simple.

Like many scientists, these note that life span increases so far — about 2.5 years per decade for the past 160 years — are due to better public health, immunizations, antibiotics and disease control, not because scientists cracked the code for longevity.

Still, both believe research is yielding tantalizing clues about the aging process itself. Even Olshansky believes that science will learn how to slow aging, maybe even find an anti-aging pill.

But it won't be easy, these scientists agree. The human body is complicated. Genes interact with other genes and with the environment in complex ways.

And we've pitted ourselves against a formidable foe: evolution.

Evolution, let's face it, selected us to be sexy — not to last forever.

We were built for "short-term use — reproduction," says Olshansky. "Once the machinery of life switches on at conception, the body sows the seeds of its own destruction."

Eating, drinking, breathing, metabolizing — all are necessary, but threaten our survival. But why?

Most theories fall into two camps, with some overlap.

The first, the "ticking clock" theories, suggest we are in the grip of a preprogrammed biological clock that regulates everything from when we crawl to when we die. According to these theories, even if you skate through the usual killers, genetically controlled breakdowns will get you in the end. Hormones and immune systems also might go through stages leading inexorably to death.

In the other camp are the "damage" theories: Life is tough, and our cells sustain damage that is incompletely or badly repaired. Eventually, this damage just wears us out, cell by cell, until something vital breaks down.

Some say cells lose their capacity for self-repair, either from environmental damage or mutations; others, that free-radicals, the byproducts of metabolism, essentially cause us to oxidize, or "rust."

Others believe the key to aging lies with glucose — blood sugar — and how it can interfere with cell function.

The Big Puzzle of Life

Researchers are hard at work in dozens of areas, with ramped-up funding by entities ranging from the National Institute on Aging to a foundation created by Larry Ellison, high-flying CEO of Oracle, a software company.

Intriguing findings, it seems, are announced nearly every week.

Dr. Nir Barzilai, director of the Institute for Aging Research at Albert Einstein College of Medicine in New York, last month reported the discovery of a genetic quirk that appears to help protect centenarians and their offspring from "bad" cholesterol.

Earlier this year, David Sinclair at Harvard Medical School found a chemical in red wine and some foods vastly increased the life span of yeast. Tom Johnson at the University of Colorado found changing a single gene can dramatically increase a worm's life span.

An Illinois scientist, Andrzej Bartke, kept a mouse alive for nearly five years — about 50 percent longer than a normal lab mouse, and the equivalent (so scientists said) of a 200-year-old human — by altering a gene that reduced its levels of blood sugar.

Sometimes the discoveries are small steps in a long process: In Seattle, Daniel Gottschling at Fred Hutchinson Cancer Research Center recently found that yeast cells in late-middle-age suddenly "switch on" genetic instability, a hallmark of cancer in humans.

If this discovery applies to human stem cells, it could "revolutionize our concepts of how cancer arises and how aging occurs," says Fred Hutchinson president Lee Hartwell, whose work on yeast revealed the genetic process of cell division, earning a Nobel Prize.

Even long-term researchers such as Austad say they're amazed at progress in the past decade. "If you told me 10 years ago that we'd have eight of these one-gene changes that substantially extend life in mice, I'd have told you that you were crazy," Austad says.

But Barzilai offers words of caution: finding the "fountain of youth" in a mouse or a worm is "terrific science," but it doesn't directly translate to humans.

For example, the very genetic variation in the worm that allows it to live longer has the exact opposite effect in humans, he says. "I'm calling for caution in interpretation of the data."

So for now, scientists and their lab mice are still nibbling away at the Big Puzzle of Life: why we get old, why we die.

Evidence seems to be mounting that exceptional longevity may depend, in part, on genes that protect from the usual killers. But scientists still disagree about basics, such as the relative effects of nature and nurture on longevity. Is it mostly about genes? Or more about skipping dessert?

In other words: People like Eva Fridell are still a mystery.

110 and counting

Until she was 106, Fridell lived alone. Then she took a fall, began having trouble walking and moved in with her grandson and his wife.

Gregg Saunders has some ideas about his grandmother's longevity: "The biggest thing has been her mental attitude," he says. "She has a real flair for living, and an inquisitive mind."

Voracious reading has been a lifelong habit, despite declining eyesight. Most recently, Fridell has enjoyed Hillary Clinton's memoir. "She's a woman with her own mind," she says admiringly. Fridell herself came from independent stock: As a child, she spent several years in an orphanage after her newly divorced mother left for Alaska to seek her fortune in gold.

She married at 17 and had three children. Her husband, Louis, died in 1974 at age 84, but their oldest child, Louise McCausland, 92, lives in Redmond. "Ninety-two and my mother is still alive!" she chortles. Fridell has five grandchildren, five great-grandchildren and great-great-grandchildren in the double digits.

Her family wonders if her light appetite contributed to Fridell's longevity. Or maybe her ability to "take things as they come," offers her 79-year-old daughter, Jean Saunders. "She just never worries."

Fridell offers another theory: "Being so damned ornery the devil doesn't want me!" she says confidently. "You've gotta have a mind of your own, that's for sure."

Bette Davis said it, but Eva Fridell is living it: Old age is no place for sissies.

Tiny clues to longevity

"She's tiny?"

Austad, the University of Idaho scientist studying aging, perks up at this detail about Fridell.

Tiny is a clue, says Austad, who is researching longevity in birds, bats and mice. Within many species, including mice, dogs and horses, he says, the small tend to live longer. Jeanne Calment, the French woman who lived to 122, was 4-foot-6.

So far, "tiny" is among many clues to an unsolved puzzle.

Some scientists believe there will be a single "magic bullet" that works for everything — perhaps protecting or repairing cells.

Anna McCormick, a biochemist and chief of the genetics and cell biology branch for the National Institute on Aging's Biology of Aging program, says she's skeptical that there is only "one aging process."

Over the years, various theories have been hyped — and then downplayed or discarded.

Now, Austad says, most scientists agree that oxygen-free radicals' damage to cells is a major player in aging. Calorie restriction, shown to extend lives in mice, might work because it limits free radicals.

But scientists disagree about whether it's the key to aging.

	Eva Fridell began a 64-year marriage to Louis Fridell at age 17.

So the search goes on, fueled by popular interest, new scientific know-how, and new levels and sources of funding such as the Ellison Medical Foundation. The Methuselah Mouse Prize — the "first-ever life extension competition" — offers cash to researchers who break the mouse age record.

Another prize will be offered for the oldest mouse geriatrically enhanced by late-onset life-extension interventions. Bartke and his 1,819-day-old mouse received the "inaugural" prize earlier this year.

Methuselah prize's co-founder, Aubrey de Grey of Cambridge University, a theoretical biogerontologist, believes that if midlife interventions prove to reverse aging, skeptics will be won over. He believes there's a 50-50 chance that by 2030 scientists will be able to repair cells faster than they're damaged. That could mean some lives already begun would span not just centuries, but millennia.

The pursuit of 'ageless bodies'

Then, we'd be back to that nagging question: Do we really want to live to be 5,000 — or even 150?

Life extension, some fear, could mean simply extending "decrepitude." As Thomas Jefferson reportedly said: "My only fear is that I may live too long. This would be a subject of dread to me."

Much depends on how that long life might happen. Would extending life simply stretch each stage like a rubber band? Or would we get to adulthood and stay there for 100 years or so, and then, like a light bulb, just blink out?

Those were some of the scenarios considered by the President's Council on Bioethics, which last month issued a report on the ethics of biotechnology and the quest for "ageless bodies."

What if we could stop the aging process in its tracks? Where would you stop? Age 20? 30? 50? Be a teenager for 130 years?

If people regularly lived to 150, many things likely would change. When would we retire? How much savings would we have to have? Would we have children at 80?

Perhaps getting old contributes to a meaningful life and societal order, wrote the bioethics panel, headed by Leon Kass of the University of Chicago.

Ultimately, the pursuit of an ageless body might prove to be "a distraction and a deformation" of what it means to be human, the panel concluded.

On a less philosophical plane, others worry about increased longevity's pressures on family, availability of caregivers and nursing-home finances. Already, diseases of old age dominate the health-care budget.

Winnie Rossi, who oversees research on exceptionally healthy aging and genetics for the NIA, says centenarians are projected to become the fastest-growing age group in the United States.

"Congress worries like crazy" about a sudden scientific breakthrough, says McCormick. There's little disagreement among scientists about the ethics of ending disease and increasing health.

But some believe there's a fuzzy line between "therapy" to end diseases and "enhancement" to extend life span. Already, disparities in life span exist among different groups, often related to lack of health-care access, in turn linked to education and income. Anti-aging research money could be better spent, suggests Rheba de Tornyay, dean emeritus of the University of Washington School of Nursing.

"I'd much rather focus on helping people live longer with what we do know," she says. For example: Many people would live longer if they shed weight and controlled diabetes. "That's not going to come in the lab under a microscope."

What to do now

In the end, Olshansky says, he and Austad are in the same camp: optimistic that scientists will — someday — learn to alter the aging process. For now, Olshansky says, none of us can lengthen our potential life span, which he attributes to genetics and luck. But we can shorten it: smoke, get fat, eschew exercise and drink a lot of alcohol.

Of course, some people do everything right and still die young — a random cell, a bit of faulty-heart "wiring," inhaling a carcinogen or getting hit by a truck.

Jeanne Calment, on the other hand, made it to 122 despite smoking for 100 years, Olshansky notes.

We'd all like to live a long, vital life, he says, but for now, there are many factors — most of them still unknown — that go into that equation. For each one of us, despite "life-span calculators" and genetic markers, the length of our life is unpredictable.

"Live each day as if it is your last," he says, "because one day you'll be right."

Carol M. Ostrom: 206-464-2249 or costrom@seattletimes.com

Copyright © 2003 The Seattle Times Company