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09/19/2002
Radicals and Aging
With my 75th birthday only a few months away, an article on an
elixir to slow the aging process naturally grabbed my attention,
especially since Bruce Ames is the proponent of this possibility,
The article, titled "Free Radical", is by Karen Wright in the
October 2002 issue of Discover magazine. The term "free
radical" might well apply to Ames himself, as well as to a certain
form of atom or molecule. In the chemical sense, a free radical is
an atom or compound or even a fragment of a compound that has
a missing electron. The free radical isn''t happy with this
situation and will do its best to strip an electron from another
compound. We chemists term this process oxidation.
Free radicals stripping away electrons in our body can break
chromosomes and do all kinds of damage. This is one reason we
are bombarded with information these days about anti-oxidants
such as Vitamins C and E and their possible benefits in fighting
off those oxidizing free radicals. Free radicals can react to break
strands of DNA and, under certain circumstances, lead to cancer.
Bruce Ames has been a force in the cancer arena ever since he
invented the Ames test back in the 1960s.
The Ames test used a particular form of the familiar Salmonella
bacterium mixed in with some rat liver enzymes in a petri dish.
Normally, this defective form of Salmonella won''t reproduce
because it lacks the ability to make a certain amino acid. If the
compound in question has the capacity to cause mutations in the
Salmonella, that is, the compound is mutagenic, some of the
Salmonella will become able to make the necessary amino acid
and visible colonies of Salmonella will grow in the dish. It''s a
relatively simple and inexpensive test.
If a compound is found to be mutagenic, there''s a fair chance it is
carcinogenic. The Ames test was put to use testing all kinds of
chemicals and a large number of them were indeed mutagenic.
A number of the chemicals were banned. Root beer for example,
is no longer flavored with safrole. The Ames test or various
modifications are used to find mutagens that warrant more
realistic animal testing to see if they are also carcinogens that
could cause cancer.
Alarmingly, the animal studies revealed that the foods we eat are
loaded with chemicals that are carcinogens. Only a few weeks
ago, we the media headlined the hazards of eating French fries.
The organic food business has promoted food grown without the
use of pesticides thought to be carcinogens. It''s hard to believe
that, in the face of these findings, Ames'' own views on pesticides
have mutated rather drastically. I remember seeing something
by him in Science many years ago when he began to espouse the
belief that many of our concerns about pesticide residues are
overblown. His opinion now is typified by an interview I found
on the Web site reason.com. In the interview, Ames points out
that there are a thousand chemicals in that cup of coffee you had
this morning. Only 22 of those chemicals have been tested in
animal studies and 17 are carcinogens! With that cup of coffee
you''ve probably drunk more carcinogens than your pesticide
intake in a whole year.
Wait! Don''t short Starbucks stock yet (unless you have some
other reason)! Ames'' contention is that, in addition to those 10
milligrams of carcinogens in our coffee, we normally eat around
1,500 milligrams of other "natural" pesticides a day. These
natural pesticides have been conjured up by plants to fight off
those nasty insects that eat them. So what''s the score? Ames
says that the animal tests are unrealistic and that the high doses
used in rat tests make the results unreliable as a measure of
carcinogenicity in humans.
Why is Ames skeptical of the animal testing? He says two
factors play key roles in the formation of mutations. One is
damage that results in "lesions" in a cell''s DNA. Damaged DNA
is a risk for cancer, but there are DNA "repair enzymes" that go
around fixing up those lesions. While these repair enzymes do a
fine job, they can''t fix all the lesions. I was surprised to read
something by Ames on the Web site users.rcn.com that says the
DNA in each cell of a rat receives about a hundred thousand
oxidative "hits" a day! By the time the rat''s a year old, the
number of lesions is about a million and in an old rat (I assume
about 3 years old) this number goes up to about 2 million.
The other factor affecting mutation is cell division. If you''ve got
a damaged cell and it divides you''ve got a mutation, I assume
because the damage is now replicated in both cells. So, both the
initial lesions and cell division contribute to the possibility of
cancer. At low doses, the main effects are due to the damage in
the DNA, the lesions. However, at the high doses, cells are
actually killed off. What''s the natural reaction of the body when
cells are killed? The body rushes in the troops to make up for the
lost cells by encouraging major cell division. This cell division
leads to more mutations, especially in the case of the older rats,
where the DNA has more lesions than in the younger ones.
Ames considers that the double-barreled effect of mutation
damage and cell division ensures that the rats will have a much
greater chance of getting cancer. Hence, Ames believes the high
dosage skews the results to the point they don''t apply to humans,
for whom the doses are relatively small. Ames is not saying that
there aren''t some bad actors. For example, smoking takes 10
years off your life and those who eat lots of fruits and veggies
have less cancer than those who don''t. So, give up smoking and
eat a healthy diet and you''re ahead of the game. On the other
hand, he doesn''t think much of the organic food bit. He feels that
if we make the fruits and veggies more expensive, people will eat
less of them so, in his opinion, it''s better to ingest a bit of
pesticide than forego those veggies. As I said, Ames is sort of a
free radical and there are those who disagree with his opinions.
However, with over 450 publications and honors such as the
National Medal of Science, Ames is not one to be dismissed
lightly - even when he states that he might have a way to prolong
our productive lives. Magazines are loaded with ads for products
claimed to prolong our lives but these are typically scams. There
have been studies that do indicate that restricting food intake in
various animals and insects can result in dramatic increases in
lifespan. Just this past week, I saw an article in the paper that
reported a study that indicates that a restricted calorie diet also
promotes a longer life in humans. With today''s trend in food
consumption in the U.S. distinctly in the opposite direction,
starvation is not likely to be a popular life extender very soon.
Ames'' approach is different. Aside from his endorsement of
fruits and veggies, he and his colleagues have been looking at
three factors that affect aging - nutritional factors, inflammation
as a risk factor for cancer and oxidation that promotes lesions in
the DNA of mitochondria. Mitochondria are the structures in a
cell that provide the fuel for the cell to function. They''re sort of
like fuel cells that burn fats and carbohydrates to produce the
fuel. However, while producing the fuel, the mitochondria give
off gobs of free radicals. Ames says there are pounds of free
radicals produced in our bodies every year. The prevalent theory
of aging is that aging is due to the damage done by these free
radicals. Ames surmised that the damage would be especially
great in the mitochondria''s DNA since that''s where most of the
free radicals originate.
Carrying this a step further, Ames figured if you wanted to slow
aging why not intervene in the mitochondria? Ciao! Married to
a biochemist of Italian extraction, Ames and his wife spend a
good bit of time in Italy. While there in the mid-1990s, a dietary
supplement was quite popular as a pick-me-up. The supplement,
acetyl-L-carnitine, also known as Alcar, was found by Italian
researchers to improve the functioning of mitochondria in rats.
Ames came back and fed Alcar to his old rats and sure enough,
they really perked up. Unfortunately, the Alcar not only goosed
up the rat''s energy but it also it increased the rate of free radical
production. Not a good thing.
Not willing to admit defeat, Ames decided to give the rats
something to fight off those free radicals. Ames chose lipoic
acid, a compound known to be an antioxidant in mitochondria.
Well, the damage to those rats'' mitochondria dropped drastically
and the rats became twice as active. Not only that, but after a
month on the new combo of Alcar and lipoic acid, the old rats''
memories improved drastically. (This involved teaching the rats
to find a platform in a swimming pool; rats hate to swim and the
old rats changed from just wandering around to find the platform
to going straight for it, as did the young rats.)
Ames formed a company to test this combo of Alcar and lipoic
acid and other nutrients on humans to see if the same increase in
energy and mental acuity results. The Discover article gives the
actual mix of Alcar and lipoic acid being tested but I''m not going
to recommend that you go to your health food store and try it.
I''m going to wait for Ames to publish his findings. Meanwhile,
I''ll take my vitamins, eat more fruits and veggies and not worry
about those pesticides.
Allen F. Bortrum
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