The Nutritional Control of Aging.

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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 nutritionally-speaking 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?

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By Ron Rosedale

Ron Rosedale, M.D. is the author of The Rosedale Diet published by HarperCollins available in most bookstores or at Amazon. For more information visit his Web site http:advancedmetaboliclabs.com/.

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