|
by Ron Rosedale M.D.
The Nutritional Control of Aging
To successfully treat any disease one must know what
disease to treat. Furthermore, treating only a symptom
of a disease will leave the underlying disease at best
unchecked. Lowering cholesterol to treat heart disease is no
better than taking a decongestant for a “runny” nose associated
with an upper respiratory infection. We evolved the
“runny” nose to help us cleanse out the infection. Symptoms
are the way that evolution has taught us how to best deal with
the disease. Treating only the symptoms often, if not usually,
makes the underlying disease worse.
When dealing with heart disease, diabetes, obesity, arthritis,
osteoporosis, autoimmune diseases and cancer, what are the
symptoms and what is the disease? Hint; these all are chronic
diseases of aging. Substitute the word “symptoms” for “disease”
and you will be much more correct. These are symptoms
of aging and the new biology of aging is teaching us that aging
itself, though not curable, is treatable. If you are not treating
aging, you are treating a symptom and you do not know if the
treatment will be worse than the “disease” that you are trying
to treat. It matters very little if 10 studies show that a drug
improves risk for heart disease if it increases risk for cancer
or other diseases of aging. What you really need to know is its
effect on mortality rate and likely therefore aging.
Much of what we know about longevity is derived from studies
of humans and animals who have broken the age barrier
for their species. The longest lived flies may survive only a few
days, mice a couple of years, and dogs for one or two decades,
depending on their size. Humans currently have the potential
to live to be at least 120 years, but few actually do. The average
life expectancy today is around 80 years old, which is impressive,
but no where near our full potential.
Growing in ranks, yet still few in number, are the exceptional
group of people who live to be 100 years old and over. Scattered
throughout the world, these centenarians are providing scientists
with a living laboratory from which they can unravel the
secrets of longevity. The reasoning is, if we can figure out why
these folks managed to live so long, we could use this information
to extend the life span for everyone.
It would be easy to dismiss longevity merely as a function
of luck, that is, simply a matter of winning the genetic lottery,
but we know this isn’t exactly true. That’s a good thing for it
means we may be able to control our own destiny. We have
been controlling the longevity destiny of laboratory animals for
decades.
Laboratory animals put on calorie restricted, though nutritionally
complete, diets provide a second and equally rich source
of information on longevity. Since the 1930s, dozens of species
have been fed calorie restricted diets, including microscopic
tiny worms, assorted rodents, and more recently, rhesus monkeys,
fellow primates that are closely related to humans. These
animals virtually always live longer -- 30 to 300 percent longer.
This would be the equivalent of a human living to be 160 - 360
years old.
At first glance, human centenarians would appear to have
very little in common with calorie restricted animals. After all,
humans can eat what they want, when they want and it appears
as if many centenarians did just that. There is no evidence that
centenarians followed a particular diet, or even had particularly
healthy life styles. Some centenarians smoked, some did not,
some exercised regularly, some did not, and some were careful
eaters, and some ate whatever they felt like.
Despite the obvious difference, there are some striking
similarities between caloric restricted laboratory animals and
free living centenarians. Centenarians and calorie restricted
animals share a particular bio-metabolic profile that distinguishes
them from their peers who die younger and sicker. We
now know the common denominators that are found in almost
all living beings-whether they are worms, mice, monkeys or
humans-that defy the odds and live beyond their expected life
span. In nearly every study, the longest lived animals share the
following traits:
- Low fasting insulin levels
- Reduction in fasting glucose
- Lower body temperature
- Low percentage of body (viceral) fat
- Reduced thyroid levels
- Low triglycerides
- Low fasting leptin levels
(Leptin is so new, that it has only recently been able to be
measured in centenarians, but it has been measured in calorie
restricted animals. Since leptin correlates and even controls
these other biomarkers in humans, this would also all but have
to be true in centenarians.)
Why are these factors shared among long-lived individuals
in all species? The most important finding to me, of the various
genome projects including the human genome project, is just
how similar are our genes to virtually all other animal species
“above” bacteria in both kind and even number. All of the
important and basic metabolic processes necessary for life are
shared among nearly all species. That means we have virtually
the same genes that allow laboratory animals to live to twice
their usual age or more.
The major differences between species and particularly
within a species, have to do more with which genes are allowed
to be read, or “expressed” than what genes are present. We
have virtually all the genes a worm has, but we don’t slither
along the ground because we have kept those worm genes
under wraps or “silenced”. Many genes, however, can be
turned on or off, and this mostly depends on their nutritional
environment. Perhaps the most important of these genes
regulate aging, and virtually the same genes appear to regulate
the same factors that determine longevity in nearly all forms of
life including humans. Caloric restricted animals may not have
been born with the profile of longevity, but their diet enabled
them to express the genes that recreate it. In other words,
eating less has reprogrammed their genes to extend their lives.
You also can create a favorable genetic environment that is likely
to not only extend your life, but help to keep you “disease“
free for as long as possible. You may actually make your body
decades younger, and turn back the clock to a time when you
weren’t weighed down with all that extra fat, or when you didn’t
have diabetes or heart disease... and you don’t have to be forced
to live in a cage on a caloric restricted diet to do so.
Why those particular factors including insulin, glucose, and
leptin? Before I can answer that, and before we talk about
how we age and the mechanisms that appear to control it, we
should talk first about why we age.
It takes energy to make babies; lots of it. Throughout life’s
history, energy has been very precious and not unlimited. Like
your bank account, any living thing must decide how its energy
currency is to be spent. The major choice is between maintenance
and repair or reproduction. This is similar to your car.
You must decide whether it is cheaper to keep repairing your
car, or whether it would be more economical to buy a new one.
Furthermore, it makes no sense to waste energy to try to make
babies when it appears there’s not enough energy available to
successfully accomplish that goal. Instead, it seems that virtually
all living forms can “switch gears”, actually switch genes, in
times of food shortage to direct energy away from reproduction
and towards mechanisms that will allow it to “hunker down”
for the long haul and thus be able to reproduce at a future
more nutritionally opportune time. In other words nature will
then allow you to live longer to accomplish its primary directive
of reproduction. It does this by turning on maintenance and
repair genes. When you are in maintenance and repair mode,
the body’s “body shop” is revved up and ready to go. Calorie
restricted animals and centenarians have measurably higher
levels of key chemicals that extend life and promote repair,
including antioxidants such as glutathione, catalase and SOD
that protect cells against damage inflicted by free radicals,
chemicals that can accelerate aging and promote disease.
They also have higher levels of very important proteins called
heat shock proteins, which protect other vital proteins from
being damaged and misshaped. Proteins communicate with
other cells by “touch” much the same way a blind person uses
braille. When a protein is misshaped, it will give bad instructions
to other cells, which will interfere with the normal functioning
of the body. The upregulation of heat shock proteins is
vital for a long, healthy life. DNA repair is also bolstered. This
all happens when you restrict calories in animals, and that has
been shown convincingly for 70 years to greatly extend their
lifespan. Thus, there is a powerful link between energy stores,
reproduction, and longevity. One could guess there must be
signals that indicate energy stores and that regulate the genetic
expression of longevity genes. One would be guessing right.
Our health and life depends on how accurately instructions
are conveyed to our cells so they can act in harmony. It is the
communication among the individual cells that will determine
our health and our life. The communication takes place by
hormones. Arguably therefore, the most important molecules
in your body that ultimately will decide your health and life
are hormones. Many would say that genes and chromosomes
are the most important molecules, however once born your
genes pretty much just sit there; hormones tell them what to
do. Certainly, the most important message our cells receive is
how and what to do with energy, for metabolism and therefore
life cannot take place without that. The two most important
hormones that deliver messages about energy and therefore
control metabolism and aging are insulin and leptin.
Metabolism can roughly be defined as the chemistry that
turns food into life, and therefore insulin and leptin are critical
to health and disease. Both insulin and leptin work together to
control the quality of one’s metabolism (and, to a significant
extent, the rate of metabolism). Insulin works mostly at the
individual cell level, telling the vast majority of cells whether
to burn or store fat or sugar and whether to utilize that energy
for maintenance and repair or reproduction. This is extremely
important, for at the individual cell level turning on maintenance
and repair equates to increased longevity, and turning up
cellular reproduction can increase the risk of cancer.
Genetic studies in simple organisms have convincingly
shown the link between energy stores, reproduction, and aging
to be at least partially mediated by insulin (which in simple
organisms also functions as growth hormone), and when insulin
signals are kept low, indicating scarce energy availability,
whether or not one, in fact, has scarce energy, maximal lifespan
can be greatly extended. Levels of insulin are largely determined
by glucose (and amino acid from protein) levels.
Glucose is an ancient fuel used even before there was oxygen
in Earth’s atmosphere by ancient organisms, for life could
and can burn glucose without oxygen; it is an anaerobic fuel.
The use of fat as fuel came later, after life in the form of plants
soaked the earth in oxygen, for you cannot burn fat without
oxygen. The primary source of energy stores that evolved in
people by far is fat, as far too many people unfortunately are
well aware of.
So where does leptin fit into this picture? Whereas insulin
largely controls individual cell metabolism, leptin, a hormone
produced by fat cells, controls the energy storage and utilization
of the entire republic of cells, you, allowing your body to
communicate with your brain about how much energy (fat) the
republic has stored, and whether it needs more, or should burn
some off, and whether it is an advantageous time nutritionallyspeaking
for the republic --you-- to reproduce or not. It is the
key player in the evolutionary tug of war between whether the
body should concentrate on reproduction or maintenance and
repair.
All of the symptoms of aging, including (type 2) diabetes,
cardiovascular disease (including heart disease and stroke),
the epidemic of obesity, osteoporosis, arthritis, even cancer
and indeed, as science is now showing, aging itself is related
to insulin and leptin communication. What does leptin do and
how do insulin and leptin operate to influence your health
to such a great extent? How do they control the laboratory
markers of longevity and how can you control them to greatly
improve your health?
|
