Defying the years URGENT UPDATE ON LONGEVITY AND RESVERATROL
OAKLAND, Calif. -- Time unravels us. Day by day, it peels away the layers of our lives until nothing is left
but the nub of our own mortality.
Human beings are the only animals on the planet capable of contemplating their own demise. We mourn,
we memorialize, we philosophize and we pray. And when it happens on that rare occasion that we "cheat"
death or "escape" our fate, we believe, just for a moment, in the myth of immortality.
Today scientists are tempting fate in ways never before imagined as they demystify the secrets of
longevity. Biochemist Bruce Ames believes that vitamins can repair damaged cells and make them
"young" again. Molecular biologist Judith Campisi is studying how to keep cells from aging.
Both believe that while there may be no actual Fountain of Youth, no scientific Dorian Gray in a Bottle,
reversal of aging and an extended life span are now on the horizon.
Bruce Ames is a chain-reaction thinker -- one thought always leads to another -- which may explain why
the senior scientist at Children's Hospital of Oakland Research Institute is so restless. Ames, 73 and wiry,
often starts a conversation sitting down but invariably finishes it standing up, practically sprinting across
his office to a blackboard to illustrate something about unattached free radicals or mitochondrial decay.
Chain-reaction thinking leads to big ideas, and Ames is a big idea man. Genes. Cancer. Nutrition. Aging.
He has tackled them all, publishing more than 450 articles and becoming one of the most frequently cited
scientists on the planet.
"I told a colleague recently that I was doing the best work in my career," says Ames, who is also a
professor of biochemistry at the University of California at Berkeley, "and he looked at me and said,
'Bruce, you've been telling me that for 30 years.' I guess that means my enthusiasm genes are
undamaged."
Ames should know. Damaged genes have been his business for half a century. Ames grew up in
Manhattan as the son of a high school chemistry teacher and a mother who wanted him to be a doctor.
Instead he became a researcher, graduating from the Bronx High School of Science before getting his
undergraduate degree at Cornell and his Ph.D. in biochemistry at the California Institute of Technology.
In the 1950s Ames was a researcher in a lab at the National Institutes of Health, investigating ways to test
for genetic mutation. His petri dish protocol ultimately proved that genes damaged by certain chemical
substances often gave rise to cancer. By the 1970s, the "Ames test" was the world's most widely used
method for identifying potential carcinogens in everything from clothing to hair dye to pharmaceuticals.
"It's just problem-solving," says Ames about his research methods. "If you have two odd facts in your head
and suddenly they fit together, you see some new way of explaining something."
That's what happened nearly a decade ago, when Ames turned his focus from cancer to aging.
How and why we age has been a mystery since humans first contemplated their own mortality. It is one of
the most complex of biological processes: The human body contains more than 250 types of cells, and
each type has its own peculiar aging characteristics.
There are scores of different theories about aging, but all of them can be broken down into two broad
camps: theories that regard aging as the result of normal wear and tear from environmental insults and
metabolic processes; and theories that regard aging as the result of a pre-programmed genetic plan, a
process that begins at birth, or even at conception, and continues until our "biological clock" runs down.
As a scientist who loves studying process almost as much as its results, Ames falls in the wear-and- tear
camp. His years of watching the cellular chaos created by cancer has given him perspective on the
degradation of cells that comes with aging.
"In 6 million years of evolution, we've gone from a short-life creature to a long-life creature," says Ames,
"and age-specific cancers have gone up. Thinking about that said to me: A lot of cancer is just about
getting old. And that got me interested in aging."
Two odd events kept jangling about in Ames' head: the rise in cancer and the increase in free radicals
with age. Free radicals are molecular miscreants, compound substances that create havoc inside cells by
stripping other molecules of their electrons. Was there a direct link between free radicals and aging? Was
it possible that free radicals actually contributed to aging?
THE TINY FURNACES
Ames began by looking at mitochondria, where free radicals are produced. Mitochondria are tiny
structures inside every cell that act like furnaces, manufacturing most of the energy that is used by the
body. Some cells with high metabolic rates, such as those in the heart muscle, contain many thousands of
mitochondria. Other types of cells may contain as few as a dozen.
As energy-producing machines go, mitochondria are spectacularly efficient. Of the oxygen consumed by
an average cell, the mitochondria convert 95 percent of it to help turn food -- fats and carbohydrates -- into
a chemical fuel known as adenosine triphosphate, or ATP. Every time we breathe, in other words, we're
giving an energy boost to our cells.
During that process, mitochondria steal electrons from oxygen molecules in order to function more
smoothly. But therein lies the problem. During those acts of larceny, a mitochondrion sometimes
"misplaces" the electrons it is stealing. Like money flying out the back of a Brink's truck careening around
a corner, these misplaced electrons -- now called free radicals -- scatter around the insides of cells,
bonding indiscriminately with other molecules.
This mischief is called oxidation, and it allows free radicals to become chromosomal rototillers, breaking
and mangling DNA at will.
Too many free radicals create a kind of cellular pollution that stiffens cell membranes and wears down
enzymes. Too much damaged DNA results in cell mutations (which can cause cancer). Both are signs of
aging.
If not for these free radicals, Ames realized, mitochondria could be a cellular Fountain of Youth.
In 1990 he and his colleagues at Berkeley announced the findings of their study. They'd discovered twice
as much free radical damage in tissues of 2-year-old rats as in those of 2-month-old rats. Ames had found
a crucial link among oxidation, DNA mutation and age: Free radical oxidation doesn't just rise with aging,
it causes it. The more that mitochondria "leak" free radicals, the more those radicals end up damaging the
mitochondria, which in turn leak even more free radicals.
This vicious cycle gets only worse with age. It is the ultimate biological irony: The thing we most need to
live -- oxygen -- is the very thing killing us.
Ames estimates that the DNA in each cell of the human body experiences at least 100,000 "hits," or
instances, of free radical damage per day.
"Living is like getting irradiated," says Ames. He admits it's a slight oversimplification, but free radicals
created by radiation do the same thing as free radicals created by breathing. "With age, despite the
mitochondria trying to keep it all in check, the level of free radicals goes up, which means the level of
oxidized protein goes up, which means the level of DNA damage goes up."
Most scientists believe that mitochondrial health is only one cog in the aging wheel.
"Aging is complex and will not be explained by one gene or mechanism," says Jerry Shay, who holds the
Distinguished Chair in Geriatric Research at the University of Texas Southwestern Medical Center. Shay
believes Ames' research is promising but that other biological processes affecting longevity must be
taken into account, since "different tissues may have fundamentally different mechanisms underlying their
maintenance and repair."
To prove that mitochondrial dysfunction actually causes us to age, Ames decided to work backward. If he
could find a way to restore mitochondrial health by lowering free radical damage, he could improve cellular
function. In essence, he could turn back the cells' biological clocks.
(Ames is in no hurry to turn back his own biological clock. He likes to joke that he gets his exercise by
"running" experiments, "skipping" the controls and "jumping" to conclusions. His wife of 40 years,
biochemist Giovanna Ferro- Luzzi, heard the joke for the 50th time recently and exacted her revenge: "She
got me a personal trainer."
Ames says he has time for only about an hour a week with the trainer, but his wife insists they walk the two
miles to their favorite Italian restaurant, Oliveto, for lunch at least three times a week.)
REINVIGORATED RATS
It was while visiting his wife's native country in the mid-1990s -- they have a house in Tuscany and an
apartment in Rome -- that Ames got the idea for how to improve mitochondrial health and perhaps slow, or
even reverse, the aging process.
A dietary supplement known as acetyl-L-carnitine, or Alcar, was sweeping Italy. The latest nutritional fad
was being marketed as a pick-me-up, and Ames understood why: Alcar is a naturally occurring
biochemical involved in the transport of fatty acids into the cell's mitochondria. In other words, Alcar helps
cells produce energy.
When Ames got back to his lab, he started feeding Alcar to his old rats.
And the old rats loved the stuff. Within weeks, they appeared re-energized, and their biochemistry was
running more smoothly. There was a problem, however. As the Alcar improved mitochondrial health, it also
appeared to increase the level of free radicals. Ames decided to add another nutritional supplement to his
rats' diets, the anti-oxidant alpha lipoic acid. Another naturally occurring chemical, lipoic acid, he thought,
should work by tuning up mitochondrial function, thereby lowering free radical oxidation.
The results were staggering. Said Ames earlier this year, after the findings of his research team were
published in the Proceedings of the National Academy of Sciences:
"With these two supplements together, these old rats got up and did the Macarena. ... The brain looks
better, they are full of energy. Everything we looked at looks more like a young animal."
Some researchers believe the hope offered by maintaining healthy cells or rejuvenating old ones is limited.
"You can achieve immortality at the cellular level, but I don't see how it would be practical in extending life
span," says Robert Lanza, the medical and scientific director of Advanced Cell Technology in Worcester,
Mass. "There's a wall at 120 years. We can continue to piece things together. But we're like tires; there
are just so many times you can be patched up."
Ames acknowledges he has not discovered the Fountain of Youth but lays claim to a Fountain of Middle
Age. The evidence, he says, lies not only in the physical rejuvenation he observed in his rats, but in their
improvements on cognition and memory tests. Says Ames: "It was the equivalent of making a 75- to
80-year-old person look and act middle-aged."
Ames looks every bit the part of an elderly gent, with his white hair, bifocals and quaint bow tie. While he
has a penchant for mixing plaids, his mind is relentlessly mixing and matching ideas.
"I was always sort of a B-student in school, but I loved reading enormously. Still do. I was always a pretty
creative thinker. I try to be a generalist. I make my living as a big picture guy, always looking for the next
big idea."
Ames put his current big idea into a pill. In 1999, he and a colleague, Tory Hagen, founded a company to
sell the energy formula as a dietary supplement. The pill, available over the Internet, includes 200
milligrams of alpha lipoic acid and 500 milligrams of acetyl-L-carnitine, but Ames says the two nutrients
just as easily can be purchased separately at any health food store.
While Ames and Hagen's company, Juvenon, licenses the supplement, the University of California holds
the patent. Juvenon has yet to make a profit. If it does, the university will get a third. Another third will go to
the university's department of molecular and cell biology, where Ames is a professor, and the remaining
third will be split by Ames and Hagen, now at the Linus Pauling Institute at Oregon State University.
Clinical human trials are ongoing. Ames, for one, is satisfied enough with the animal results that he takes
a dose of his own supplement twice a day. He admits he hasn't noticed any significant changes in himself
just yet.
"Is it a reversal of aging or just a slowing?" he asks himself out loud. "The rats seem to do better on the IQ
test as well as the treadmill test, so that looks like a reversal. ...
"I don't want to over-hype it. If you're an old rat, it looks very good. But we still have to wait for the results
from the human trials. There's every reason to think it's going to work in people. I'm very optimistic."
BY AMY ELLIS NUTT
STAR-LEDGER STAFF
OAKLAND, Calif. -- Time unravels us. Day by day, it peels away the layers of our lives until nothing is left
but the nub of our own mortality.
Human beings are the only animals on the planet capable of contemplating their own demise. We mourn,
we memorialize, we philosophize and we pray. And when it happens on that rare occasion that we "cheat"
death or "escape" our fate, we believe, just for a moment, in the myth of immortality.
Today scientists are tempting fate in ways never before imagined as they demystify the secrets of
longevity. Biochemist Bruce Ames believes that vitamins can repair damaged cells and make them
"young" again. Molecular biologist Judith Campisi is studying how to keep cells from aging.
Both believe that while there may be no actual Fountain of Youth, no scientific Dorian Gray in a Bottle,
reversal of aging and an extended life span are now on the horizon.
Bruce Ames is a chain-reaction thinker -- one thought always leads to another -- which may explain why
the senior scientist at Children's Hospital of Oakland Research Institute is so restless. Ames, 73 and wiry,
often starts a conversation sitting down but invariably finishes it standing up, practically sprinting across
his office to a blackboard to illustrate something about unattached free radicals or mitochondrial decay.
Chain-reaction thinking leads to big ideas, and Ames is a big idea man. Genes. Cancer. Nutrition. Aging.
He has tackled them all, publishing more than 450 articles and becoming one of the most frequently cited
scientists on the planet.
"I told a colleague recently that I was doing the best work in my career," says Ames, who is also a
professor of biochemistry at the University of California at Berkeley, "and he looked at me and said,
'Bruce, you've been telling me that for 30 years.' I guess that means my enthusiasm genes are
undamaged."
Ames should know. Damaged genes have been his business for half a century. Ames grew up in
Manhattan as the son of a high school chemistry teacher and a mother who wanted him to be a doctor.
Instead he became a researcher, graduating from the Bronx High School of Science before getting his
undergraduate degree at Cornell and his Ph.D. in biochemistry at the California Institute of Technology.
In the 1950s Ames was a researcher in a lab at the National Institutes of Health, investigating ways to test
for genetic mutation. His petri dish protocol ultimately proved that genes damaged by certain chemical
substances often gave rise to cancer. By the 1970s, the "Ames test" was the world's most widely used
method for identifying potential carcinogens in everything from clothing to hair dye to pharmaceuticals.
"It's just problem-solving," says Ames about his research methods. "If you have two odd facts in your head
and suddenly they fit together, you see some new way of explaining something."
That's what happened nearly a decade ago, when Ames turned his focus from cancer to aging.
How and why we age has been a mystery since humans first contemplated their own mortality. It is one of
the most complex of biological processes: The human body contains more than 250 types of cells, and
each type has its own peculiar aging characteristics.
There are scores of different theories about aging, but all of them can be broken down into two broad
camps: theories that regard aging as the result of normal wear and tear from environmental insults and
metabolic processes; and theories that regard aging as the result of a pre-programmed genetic plan, a
process that begins at birth, or even at conception, and continues until our "biological clock" runs down.
As a scientist who loves studying process almost as much as its results, Ames falls in the wear-and- tear
camp. His years of watching the cellular chaos created by cancer has given him perspective on the
degradation of cells that comes with aging.
"In 6 million years of evolution, we've gone from a short-life creature to a long-life creature," says Ames,
"and age-specific cancers have gone up. Thinking about that said to me: A lot of cancer is just about
getting old. And that got me interested in aging."
Two odd events kept jangling about in Ames' head: the rise in cancer and the increase in free radicals
with age. Free radicals are molecular miscreants, compound substances that create havoc inside cells by
stripping other molecules of their electrons. Was there a direct link between free radicals and aging? Was
it possible that free radicals actually contributed to aging?
THE TINY FURNACES
Ames began by looking at mitochondria, where free radicals are produced. Mitochondria are tiny
structures inside every cell that act like furnaces, manufacturing most of the energy that is used by the
body. Some cells with high metabolic rates, such as those in the heart muscle, contain many thousands of
mitochondria. Other types of cells may contain as few as a dozen.
As energy-producing machines go, mitochondria are spectacularly efficient. Of the oxygen consumed by
an average cell, the mitochondria convert 95 percent of it to help turn food -- fats and carbohydrates -- into
a chemical fuel known as adenosine triphosphate, or ATP. Every time we breathe, in other words, we're
giving an energy boost to our cells.
During that process, mitochondria steal electrons from oxygen molecules in order to function more
smoothly. But therein lies the problem. During those acts of larceny, a mitochondrion sometimes
"misplaces" the electrons it is stealing. Like money flying out the back of a Brink's truck careening around
a corner, these misplaced electrons -- now called free radicals -- scatter around the insides of cells,
bonding indiscriminately with other molecules.
This mischief is called oxidation, and it allows free radicals to become chromosomal rototillers, breaking
and mangling DNA at will.
Too many free radicals create a kind of cellular pollution that stiffens cell membranes and wears down
enzymes. Too much damaged DNA results in cell mutations (which can cause cancer). Both are signs of
aging.
If not for these free radicals, Ames realized, mitochondria could be a cellular Fountain of Youth.
In 1990 he and his colleagues at Berkeley announced the findings of their study. They'd discovered twice
as much free radical damage in tissues of 2-year-old rats as in those of 2-month-old rats. Ames had found
a crucial link among oxidation, DNA mutation and age: Free radical oxidation doesn't just rise with aging,
it causes it. The more that mitochondria "leak" free radicals, the more those radicals end up damaging the
mitochondria, which in turn leak even more free radicals.
This vicious cycle gets only worse with age. It is the ultimate biological irony: The thing we most need to
live -- oxygen -- is the very thing killing us.
Ames estimates that the DNA in each cell of the human body experiences at least 100,000 "hits," or
instances, of free radical damage per day.
"Living is like getting irradiated," says Ames. He admits it's a slight oversimplification, but free radicals
created by radiation do the same thing as free radicals created by breathing. "With age, despite the
mitochondria trying to keep it all in check, the level of free radicals goes up, which means the level of
oxidized protein goes up, which means the level of DNA damage goes up."
Most scientists believe that mitochondrial health is only one cog in the aging wheel.
"Aging is complex and will not be explained by one gene or mechanism," says Jerry Shay, who holds the
Distinguished Chair in Geriatric Research at the University of Texas Southwestern Medical Center. Shay
believes Ames' research is promising but that other biological processes affecting longevity must be
taken into account, since "different tissues may have fundamentally different mechanisms underlying their
maintenance and repair."
To prove that mitochondrial dysfunction actually causes us to age, Ames decided to work backward. If he
could find a way to restore mitochondrial health by lowering free radical damage, he could improve cellular
function. In essence, he could turn back the cells' biological clocks.
(Ames is in no hurry to turn back his own biological clock. He likes to joke that he gets his exercise by
"running" experiments, "skipping" the controls and "jumping" to conclusions. His wife of 40 years,
biochemist Giovanna Ferro- Luzzi, heard the joke for the 50th time recently and exacted her revenge: "She
got me a personal trainer."
Ames says he has time for only about an hour a week with the trainer, but his wife insists they walk the two
miles to their favorite Italian restaurant, Oliveto, for lunch at least three times a week.)
REINVIGORATED RATS
It was while visiting his wife's native country in the mid-1990s -- they have a house in Tuscany and an
apartment in Rome -- that Ames got the idea for how to improve mitochondrial health and perhaps slow, or
even reverse, the aging process.
A dietary supplement known as acetyl-L-carnitine, or Alcar, was sweeping Italy. The latest nutritional fad
was being marketed as a pick-me-up, and Ames understood why: Alcar is a naturally occurring
biochemical involved in the transport of fatty acids into the cell's mitochondria. In other words, Alcar helps
cells produce energy.
When Ames got back to his lab, he started feeding Alcar to his old rats.
And the old rats loved the stuff. Within weeks, they appeared re-energized, and their biochemistry was
running more smoothly. There was a problem, however. As the Alcar improved mitochondrial health, it also
appeared to increase the level of free radicals. Ames decided to add another nutritional supplement to his
rats' diets, the anti-oxidant alpha lipoic acid. Another naturally occurring chemical, lipoic acid, he thought,
should work by tuning up mitochondrial function, thereby lowering free radical oxidation.
The results were staggering. Said Ames earlier this year, after the findings of his research team were
published in the Proceedings of the National Academy of Sciences:
"With these two supplements together, these old rats got up and did the Macarena. ... The brain looks
better, they are full of energy. Everything we looked at looks more like a young animal."
Some researchers believe the hope offered by maintaining healthy cells or rejuvenating old ones is limited.
"You can achieve immortality at the cellular level, but I don't see how it would be practical in extending life
span," says Robert Lanza, the medical and scientific director of Advanced Cell Technology in Worcester,
Mass. "There's a wall at 120 years. We can continue to piece things together. But we're like tires; there
are just so many times you can be patched up."
Ames acknowledges he has not discovered the Fountain of Youth but lays claim to a Fountain of Middle
Age. The evidence, he says, lies not only in the physical rejuvenation he observed in his rats, but in their
improvements on cognition and memory tests. Says Ames: "It was the equivalent of making a 75- to
80-year-old person look and act middle-aged."
Ames looks every bit the part of an elderly gent, with his white hair, bifocals and quaint bow tie. While he
has a penchant for mixing plaids, his mind is relentlessly mixing and matching ideas.
"I was always sort of a B-student in school, but I loved reading enormously. Still do. I was always a pretty
creative thinker. I try to be a generalist. I make my living as a big picture guy, always looking for the next
big idea."
Ames put his current big idea into a pill. In 1999, he and a colleague, Tory Hagen, founded a company to
sell the energy formula as a dietary supplement. The pill, available over the Internet, includes 200
milligrams of alpha lipoic acid and 500 milligrams of acetyl-L-carnitine, but Ames says the two nutrients
just as easily can be purchased separately at any health food store.
While Ames and Hagen's company, Juvenon, licenses the supplement, the University of California holds
the patent. Juvenon has yet to make a profit. If it does, the university will get a third. Another third will go to
the university's department of molecular and cell biology, where Ames is a professor, and the remaining
third will be split by Ames and Hagen, now at the Linus Pauling Institute at Oregon State University.
Clinical human trials are ongoing. Ames, for one, is satisfied enough with the animal results that he takes
a dose of his own supplement twice a day. He admits he hasn't noticed any significant changes in himself
just yet.
"Is it a reversal of aging or just a slowing?" he asks himself out loud. "The rats seem to do better on the IQ
test as well as the treadmill test, so that looks like a reversal. ...
"I don't want to over-hype it. If you're an old rat, it looks very good. But we still have to wait for the results
from the human trials. There's every reason to think it's going to work in people. I'm very optimistic."
BY AMY ELLIS NUTT
STAR-LEDGER STAFF
These statements have not been evaluated by the Food and Drug Administration. These products are not
intended to diagnose, treat, cure or prevent the medical conditions or diseases highlighted on this page. They
are only intended as a nutritional support. Always check with your health care professional before starting a
supplemental program. DISCLAIMER
intended to diagnose, treat, cure or prevent the medical conditions or diseases highlighted on this page. They
are only intended as a nutritional support. Always check with your health care professional before starting a
supplemental program. DISCLAIMER
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I have put together 3 anti-aging - longevity programs that can fit into most anyone's
budget and intensity levels. These are based on 30 years of anti-aging research
and clinical experience.
The first 2 include Alpha Lipoic Acid, Acetyl L-Carnitine, Green Tea Ext, Grape Seed
Ext, CoQ10, 2,000 IU's D3, Omega 3 Fatty Acids EPA/DHA, 500mgs -1000 mgs C,
along with a complete multiple with all essential nutrients in high theraputic amounts.
The last one is the best combination of these or others that I could come up with at
the $50.00 cost a month level.
Program # 1 is from Orthomolecular Formulations and NSI and includes
O M Complete , O M Extend & NSI Longevatrol Stabilized Red Wine
Polyphenol Complex. (1 cap 2 x daily w/meals) This program is for those
that can afford about $130.00 a month.
Program # 2 is from NSI and it includes NSI Synergy Supreme Multi-Vitamin
Version 3 (6 caps 2x daily w/meals) & NSI Mega EFA (2 caps 2 x daily
w/meals) along with NSI Longevatrol Stabilized Red Wine Polyphenol
Complex (1 cap 2x daily w/meals). This program is around $100.00 a month.
Program # 3 is from NSI and it includes NSI Mitochondrial Energy Booster (2
caps 2x daily w/meals) & NSI Longevatrol Stabilized Red Wine Polyphenol
Complex (1 cap 2x daily with meals) This program costs about $56.00 a
month.
budget and intensity levels. These are based on 30 years of anti-aging research
and clinical experience.
The first 2 include Alpha Lipoic Acid, Acetyl L-Carnitine, Green Tea Ext, Grape Seed
Ext, CoQ10, 2,000 IU's D3, Omega 3 Fatty Acids EPA/DHA, 500mgs -1000 mgs C,
along with a complete multiple with all essential nutrients in high theraputic amounts.
The last one is the best combination of these or others that I could come up with at
the $50.00 cost a month level.
Program # 1 is from Orthomolecular Formulations and NSI and includes
O M Complete , O M Extend & NSI Longevatrol Stabilized Red Wine
Polyphenol Complex. (1 cap 2 x daily w/meals) This program is for those
that can afford about $130.00 a month.
Program # 2 is from NSI and it includes NSI Synergy Supreme Multi-Vitamin
Version 3 (6 caps 2x daily w/meals) & NSI Mega EFA (2 caps 2 x daily
w/meals) along with NSI Longevatrol Stabilized Red Wine Polyphenol
Complex (1 cap 2x daily w/meals). This program is around $100.00 a month.
Program # 3 is from NSI and it includes NSI Mitochondrial Energy Booster (2
caps 2x daily w/meals) & NSI Longevatrol Stabilized Red Wine Polyphenol
Complex (1 cap 2x daily with meals) This program costs about $56.00 a
month.