As Centarians Multiply, scientists pursue clues to oldest age. Hint: It's not just genes

[Guest guest]

Looking Ahead to The Days of Old

By Rita Zeidner

Washington Post

The tattoo on Lloyd Brown's right arm, marking his tour on the USS New

Hampshire, is faded. But his memory of the day he was sworn into the Navy is

not.

" Yep, April 6, 1918, " he says, clearly pleased with his powers of recall

that at other times have proven a bit spotty. The military records his

daughter, Espina, keeps in a scrapbook at Brown's home in Charlotte

Hall, Md., confirm the date.

Brown, who turns 105 on Thursday, can recall much of a remarkable life

that has spanned three centuries. Among his most vivid days are those he

spent on Navy ships -- the first aboard the coal-burning New Hampshire,

guarding the North Atlantic during the final years of World War I.

" Holystoning, " a laborious process sailors of his era used to keep the decks

clean of coal dust, made a lasting impression.

" We'd take some sand and push it around with a brick all day, " he recalls.

His second naval tour took a more leisurely pace: playing the cello in the

admiral's orchestra aboard the USS Seattle during the Roaring '20s.

Brown would spend most of the '30s and '40s as a fireman for Engine

Company 16 -- when the three-story firehouse at 13th and K streets " was the

tallest building on the block, " he says.

Once considered a medical curiosity, centenarians like Brown are the

fastest growing segment of the U.S. population, according to the Census

Bureau. Numbering about 71,000 today -- a 35 percent increase since 1990 --

their ranks are expected to swell tenfold over the next 40 years and to leap

past a million once the first baby boomers come of age in 2046.

Their representation in the larger population also is building. In the

early 1900s, only about 1 in 100,000 lived into the triple digits; now it's

about 1 in 10,000.

" Centenarians are raising the bar for all of us, " said geriatrician

Perls, director of the New England Centenarian Study, a Boston

University-based research project launched 10 years ago to examine factors

that may contribute to extreme longevity worldwide. " People who are 80 or 85

aren't so old anymore. "

Today, Brown spends most of his days padding around his one-story rambler,

where, by choice, he lives alone. A caretaker helps him with bathing, and

Espina drops by daily to chat and bring him meals. Weather permitting, Brown

will hop into his golf cart and drive across his lawn to pick up his mail.

For the most part, though, he prefers to stay indoors and read the paper or

watch TV news. He doesn't care much for fictional dramas.

" I have trouble following the story line, " he says. " Too many characters. "

He still has a driver's license but, to his daughter's relief, hasn't

taken his car out lately. He's taken the golf cart down Route 5 instead.

" He headed out to the veterans hall, " Espina recalls. " He wanted to see

what was going on. "

Growth in the number of centenarians like Brown can be partly explained by

better care of the very young -- and a corresponding decrease in infant

mortality. But myriad other factors -- among them education, environment,

genetics and diet, not to mention dumb luck -- also contribute to longevity.

Perls, along with researchers crossing the boundaries of traditional

scientific disciplines, hope to gain a better understanding of how much of

that advantage is attributable to good living and how much to good genes.

" Living to 100 is basically like hitting the lottery, " said Perls. " You

have all these factors, but, like lottery numbers, they have to line up in

the right way. "

Collecting Clues

Though we all know of instances where longevity seems to run in the

family, a series of recent studies downplays the role of genetics,

emphasizing instead the role of good habits learned at an early age.

A landmark study of Swedish twins published in 1998 calculated the

likelihood that longevity was inherited at 20 to 30 percent. Put another

way, behavioral and environmental factors, including whether the

participants smoked or were overweight, accounted for at least 70 percent of

the variations in age at death.

The message was underscored by a 2001 study of 34,000 Seventh-Day

Adventists in California. After tracking participants for 12 years beginning

in the 1980s, researchers linked five common Adventist lifestyle practices

-- such as regular exercise, a vegetarian diet and consumption of small

servings of nuts five to six times a week -- to a longer-than-average life

expectancy.

Scientists calculated that the life expectancy of a 30-year-old vegetarian

Adventist woman was 85.7 years, and 83.3 years for a vegetarian Adventist

man. This exceeded the life expectancies of other Californians by 6.1 years

for women and 9.5 years for men.

" This was a group of people that were doing everything our mothers tell us

to do, except for cleaning our plates, " said Perls.

Meanwhile, life expectancy fell nine to 10 years for Adventists who were

overweight, former smokers and non-vegetarian, and who did not exercise or

eat nuts regularly.

But other research, including some that stems from data collected through

the Centenarian Study, argues for the familial link -- a theory consistent

with the experience of Brown and his kin. Though two siblings died in their

eighties, his older sister died two years ago at 105.

The same year findings were published on the Swedish twins, Perls showed

that people with a centenarian sibling have a four to five times greater

chance of living to age 91 than people whose siblings died in their

seventies. Later he discovered that men with a centenarian sibling were 17

times more likely to reach 100; women with a centenarian sibling were 8.5

times as likely to reach triple digits.

The findings don't necessarily contradict the Swedish study; rather, it

might be that an improved shot at only extreme longevity -- living past 100

-- is shared among siblings, according to Perls.

" To get to your 100's, that formula might be different, " he says.

Scientists are just beginning to gain insights into how genetics enters

into the longevity equation. Not all centenarians follow the Adventist model

-- Lloyd Brown continues to puff on a pipe daily, a habit he picked up

decades ago. Plus, even as a young father, he was far more likely to pick up

his cello than a football, according his daughter, still a relative

youngster at 64.

The Genetic Factor

Today there is growing evidence that not one but various biogenic forces

may work together -- either to prevent some of the ravages of aging or to

assist in damage control. At least some of these genes, it seems, are passed

down.

" Nobody thinks there's going to be [just] one gene that leads to

longevity, " said Evan Hadley, associate director for geriatrics at the

National Institutes of Health.

In 2001, a team from Harvard and two Boston hospitals identified a region

on Chromosome 4 -- one of 23 chromosomes that make up the human genetic

blueprint -- that is likely to contain a gene or genes associated with

extraordinary life expectancy.

Subsequent studies led to the discovery that a gene called microsomal

transfer protein (MTP) was responsible for the link between the chromosomal

region and longevity. This gene plays an important role in cholesterol

transport and one variation of the gene, common among the centenarians in

the study, decreases one's risk for cardiovascular disease.

" It is not a surprise, " said Perls, " that we would find a gene related to

cardiovascular health since heart disease is the number-one killer among

older people. Centenarians must have increased resistance to this and other

age-related diseases in order to achieve their remarkable ages. "

In the early 1990s studies with tiny worms at the University of California

at San Francisco showed that a single mutation in the daf-2 gene doubled the

worms' life span. More recently, UC researchers extended the worms' life

span sixfold. Researchers hope the findings may one day lead to human

therapies that address oxidative damage (cancer and cardiovascular disease,

for instance) and protein aggregation (diseases such as Parkinson's,

Alzheimer's and Huntington's).

Adding one more piece to the genetic puzzle, researchers at the Albert

Einstein College of Medicine in New York last year found that centenarians

tend to have super-sized cholesterol molecules. Smaller particles,

researchers now believe, are more easily embedded in the blood vessel walls

and contribute to the fatty buildups that lead to heart attacks and strokes.

The study, published in the Journal of the American Medical Association,

suggested that the trait of over-sized cholesterol is inherited.

Healthy to the End

If the pickings seemed slim for women seeking male partners during the

conventional dating years, the prospects only get poorer: Fewer than 20

percent of centenarians in the United States today are men, a statistic

expected to remain relatively unchanged over time.

Worldwide, the differential is even more pronounced, with women

centenarians outnumbering men by about 9 to 1. The only exception appears to

be in cultures that subject women to practices such as female infanticide

and bride-burning, says Perls in his book, " Living to 100: Lessons in Living

to Your Maximum Potential at Any Age " (Basic Books, 1999).

The small consolation is that those men who do see 100 will most likely be

in better cognitive and physical shape than women their age, says Perls. Why

is unclear, but one theory holds that in light of men's shorter life spans,

those who do make it to 100 must be particularly hardy.

In any case, data collected through the centenarian study tends to shatter

the stereotype of the long-suffering geezer. In fact, the profile of

centenarians emerging from the New England study is that of lives spent, for

the most part, in exceptionally good health, with sickness or frailty only

near the end.

" It's the idea that the older you get, the healthier you've been, " said

Perls.

That's been the pattern for Brown, who but for a gallbladder flare-up

decades ago and a hip broken after a fall in the early 1990s -- when it was

discovered he had exceptionally strong bones, despite the fracture -- never

spent a day sick in bed.

His daughter, who admits to having a long list of health issues, jokes,

" The doctor tells me to come back in six months. He says to my dad, 'I'll

see you in a year.' " •

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How Long Might You Stick Around?

The average person living in an industrialized nation has the genetic

makeup to hang on until 87, barring unforeseen circumstances. But whether

you reach that point (or live even longer) depends on six core criteria --

attitude, genes, exercise, interests, nutrition and smoking, according to

Perls, director of the New England Centenarian Study at Boston

University. (Take the first letter of each factor, revising the last to read

" Get rid of smoking, " its intent, and guess what it spells: AGEING.)

For an estimate of how long you'll be around, together with a detailed

explanation of the role each factor plays in longevity, check out Perls's

online calculator at www.livingto100.com.

Want a simpler test? Try this.

Assume you'll live to be 87. Then add or subtract years based on the

following:

Attitude Are you optimistic? Do you generally approach life in good

humor? Are you able to let go of things that are stressful (as opposed to

dwelling on them)? If no, subtract five years.

Genes Do you have some family members who have lived into their nineties

or later? If yes, add 10 years, since exceptional longevity runs strongly in

families.

Exercise Do you set aside at least 30 minutes three days a week to

exercise? Be honest. If no, subtract five years.

Interests Do you do things that are cognitively challenging on a regular

basis? Yes gets you five years.

Nutrition Do you have a diet that facilitates saying lean? Subtract five

years if you don't.

(Get rid of) Smoking If you smoke, subtract 10 years. You knew that.

-- Rita Zeidner