X-Message-Number: 31075
Date: Tue, 23 Sep 2008 09:27:08 -0700 (PDT)
From: 
Subject: Secrets of the 'Wellderly'

[It still astounds me how little is apparently known about the reasons for
the longevity of supercentenarians. I suspect conserved autophagy to be a
key element.]


The Wall Street Journal
SCIENCE JOURNAL
SEPTEMBER 19, 2008
Secrets of the 'Wellderly'
Scientists Hope to Crack the Genetic Code of Those Who Live the Longest
By ROBERT LEE HOTZ

As the oldest person in the world, Henrikje van Andel-Schipper attributed her

longevity to a slice of pickled herring and a tumbler of orange juice every day.
If pressed, she'd say tartly that 'breathing' also helped prolong life.


When this Dutch dowager died in 2005 at age 115, researchers discovered that she
had almost none of the chronic physical or mental ailments associated with
aging, according to a postmortem medical assessment published last month in the
journal Neurobiology of Aging. She supported herself until she was 105. Up to
her death, she was more alert and engaged than people half her age, cognitive
testing showed. Indeed, when the anatomists actually counted her neurons, they
discovered she had the brain of a woman 50 years younger.

'She was unbelievable,' recalls neuroscientist Gert Holstege at the Groningen
University Medical Center in the Netherlands, who documented her unusual
well-being.

Whatever the virtues of fish and fruit juice, the secret of her longevity may

have been hidden among her genes. Ascetic health habits apparently only take you
so far; a surprising number of supercentenarians smoked, ignored their
cholesterol and avoided exercise, research shows.

Based on animal experiments, gerontologists believe that one key to a healthy,
longer lifespan may be found in a few master genes that affect cellular
responses to famine, drought and other survival stresses. The more active these
genes are, the longer an organism seems to survive -- at least in the
laboratory. Moreover, researchers are convinced that some genes may protect us
against the risks of heart disease, diabetes, cancer and dementia.

Among the elite of the aged -- those who live a century or more free of disease
and mental ills -- researchers are seeking the genetic secrets of a longer,
healthier life. In their quest, teams around the world are scrutinizing the
oldest of the old -- elderly Ashkenazi Jews in New York, rural centenarians in
the state of Georgia, century-old siblings in Holland and vigorous retirees in

Okinawa -- as living test tubes in which nature has concentrated a vital essence
of longevity.

Discuss Aging
Do you think it will be possible for scientists to 'engineer' a significantly
longer life for us all? Would you like to live to be 100 or more? Do you know
anyone who has? Share your thoughts in our online forum.

Instead of focusing on what goes wrong as we age, these researchers want to
understand why some people live so long without getting very sick. If they
succeed, scientists one day may be able to do for humankind what they can
already do for yeast, worms and mice: dramatically increase the normal life
span. 'Our hypothesis is that in order to live to 100 or more, you need sets of
genes that protect you, by delaying aging and preventing age-related diseases,'
says Nir Barzilai, head of the Longevity Genes Project at Albert Einstein
College of Medicine in New York.

Already there are hints.

Earlier this month, researchers at the Pacific Health Research Institute in
Hawaii analyzing elderly Japanese-American men reported that a single
biochemical misprint in the DNA typography of a gene called FOXO3A appeared to
double or triple the chance of living to be 100 years old. They compared
variations of five genes thought to influence aging in 213 men aged 95 or older
to DNA samples from a group of 402 men who had died before reaching age 81.

Only the one variant stood out among the eldest. 'If you got two copies of this

gene -- inheriting one from each parent -- you hit the jackpot,' says geriatrics
expert Bradley Willcox who conducted the study.

Few of us, though, live to be 100. Even fewer can do so without suffering
chronic ills associated with aging. All told, there are only 79 men and women

alive today aged 110 years old or more, according to the Los Angeles Gerontology
Research Group.

Recommended Reading
Researchers are seeking the genetic secrets of a longer, healthier life by
studying the oldest of the old in Okinawa, Georgia and New York.
Earlier this month, researchers at Hawaii's Pacific Health Research Institute
reported in The Proceedings of The National Academy of Sciences their discovery
of a gene that appears to double or triple the chance of living to be 100 years
old. Genomic researchers at the Scripps Research Institute and the J. Craig

Venter Institute are sequencing hundreds of genes drawn from people 80 and older

with no history of chronic disease to unlock the genetic secrets behind lifelong
health.

When Henrikje van Andel-Schipper died in 2005 at 115, she was the oldest person
in the world, yet she had almost none of the ailments associated with aging,
researchers reported in the journal Neurobiology of Aging.

The Los Angeles Gerontology Group maintains official lists of those around the
world like her who've reached super-centenarian status [ndash ] the age of 110
years or more.



To pinpoint hereditary sources of longevity, researchers at the Scripps Research

Institute in La Jolla, Calif., are recruiting 2,000 healthy people over 80 years
old to compare the entire genetic sequences of these 'wellderly' to those from
people who died of common age-related illnesses before they reached 80.

'A great many people carry the genes that cause heart attack, cancer and other
diseases, but some have modifier genes that cancel out their risk,' says Eric
Topol, director of Scripps Genomic Medicine. 'We believe they actually have an
inborn protection from aging.'
In the study's first phase, Dr. Topol and his colleagues have targeted
variations of 100 genes that may influence aging. They plan to broaden their
search soon to 500 genes and then to entire genomes.


'What we are learning is that nature has found a solution in certain individuals
to combat certain disease risks,' said Samuel Levy, director of human genomics
at the J. Craig Venter Research Institute in Rockville, Md., which is
collaborating on the study.

Recent insights into the genetics of aging among simple organisms are stoking
their enthusiasm. In January, for example, gerontologist Valter Longo at the
University of Southern California reported that by altering two genes he made
yeast that lived 10 times longer than normal. 'We can really reprogram the

lifespan of these organisms,' he said. In March, scientists at the University of
Washington identified 15 genes regulating lifespan in yeast and worms that
resemble genes found in humans. At least three companies are working
independently on potential therapies based on the discovery that life span in
mammals may be regulated partly by genetically controlled enzymes called
sirtuins.

Many experts in aging are skeptical. 'We seem to know a lot about longevity in
worms, but we don't know if any of it is relevant for humans,' says Jan Vijg,
who studies the genomics of aging at the Albert Einstein medical college. 'The
problem is that we don't really know the basic cause of aging.'

Lifestyle, diet, education, exercise and health care are crucial to longevity.
Just in the U.S., Asian-American women in New Jersey live on average to be 91,
for example, while Native American men in South Dakota live to be 58, Harvard
University researchers reported.

Earlier this year, researchers at the U.K.'s University of Cambridge and the
Medical Research Council reported that people who exercise regularly, don't
smoke, limit their alcohol intake and eat five servings of fruit and vegetables
a day live, on average, 14 years longer than people who didn't.

Yet, there is little evidence of an abstemious lifestyle among the 450 people

between the ages of 95 and 110 enrolled in the Longevity Genes Project at Albert

Einstein College of Medicine. There are no vegetarians. At least a third of them
were obese in middle-age. A third have been smoking tobacco for 40 years or
more, despite health warnings. 'I have a woman who recently celebrated 91 years
of cigarette smoking,' says Dr. Barzilai. 'She is 106 now.'

Robert Lee Hotz shares recommended reading on this topic and responds to reader
comments at WSJ.com/OnlineToday. Email him at 

Copyright 2008 Dow Jones & Company, Inc.

Rate This Message: http://www.cryonet.org/cgi-bin/rate.cgi?msg=31075