Posted on 12/26/2002 7:47:46 AM PST by theFIRMbss
Living Longer: Calories that Count
By Dr. Roy Walford
The maximum life span of humans is about 110 years; of mice, about 39 months. Thus far, mice over 39 months of age have not been produced by anything except selective restriction of calories in the diet. Calorie restriction (CR) has extended the 39-month maximum life span of mice to an impressive 56 months, which would correspond proportionally to a 158 year-old human. And the long-lived mice stay youthful in appearance, in mental and physical abilities, and show enhanced resistance to disease. These well-established facts are why the CR diet is now one of the principal areas of research in gerontology, and is receiving major emphasis from the National Institute on Aging.
So let's run briefly through the history of this remarkable CR phenomenon, and discuss what precisely it is, how and why it works to retard aging (to the extent that this is known), and whether it will work as dramatically in humans as it does in rodents. Historically, the field's development can be divided into five phases:
(1) The demonstration that mean and maximum life spans are greatly extended in rodents by a CR diet. This was first shown at Cornell University as long ago as 1935, and has been confirmed dozens of times elsewhere, right up to the present time. Also, the frequencies of a wide variety of diseases -- including virtually all types of cancer, cardiovascular disease, diabetes, kidney disease, autoimmune disease, ocular degeneration, plus others -- have been documented as being greatly reduced in CR animals. The reduction ranges from twofold to as much as tenfold. (For example, 50 percent of female control mice of a particular genetic strain develop breast cancer, but only 5 percent of the same strain if on a CR diet.)
(2) CR's effect on life span has been dramatic in every species so far tested, from invertebrates (spiders, worms, etc) up through fish and rodents. One may cautiously presume that it may be a "general" effect, and not simply a rodent phenomenon.
(3) How CR animals look, how they respond in tests of mental and physical abilities, their levels of blood sugar, insulin, blood lipids, blood pressure, and essentially all their physiologic parameters correspond to those of chronologically much, much younger animals. This area of research, namely the effect of CR on physiologic systems, was first opened in my laboratory in the early 1970s, with the immune system as representative yard stick. Over the past twenty years, we've continued this research for biochemical, endocrine, molecular genetic, and behavioral markers in a number of university laboratories.
(4) The search for the mechanism whereby a selective restriction of calories exerts such global effects upon so many systems; and finally
(5) The question whether those same effects would obtain in primates including humans. Can human aging be slowed and life span extended by a CR diet, and by how much?
What precisely is the CR diet? Giving animals fewer calories than they would consume by choice makes them live longer, with enhanced faculties, and with fewer diseases, but these fewer calories cannot come from the mouse counterpart of the typical junky American diet. While reduced in calories, the quality of the diet must be increased so that essential nutrients like vitamins, minerals, and amino acids are not reduced. The reason the semi-starved populations in parts of Africa or the Orient don't live longer is that they are not only calorie restricted, they are malnourished. The "adequate nutrition" side of CR is essential. Given that, then the fewer the calories, the longer the life, down to about 50 percent restriction in rodents, and the other beneficial effects noted above follow along proportionately. In other words, CR is not an all or none phenomenon. Even 10 percent restriction has a measurable beneficial effect. Of course, there is a lower limit. Below 50 percent takes you into actual calorie starvation, and the death rate increases. Fifty percent restriction is not recommended for humans. That's too close to being too few in the way of calories!
What is the mechanism behind CR's marvelous effects? If we knew the mechanism, perhaps we could achieve the same results by an easier method than restricting food intake. One thing is certain. The effect is only related to calories. As long as essential nutrients are present, the relative amounts of protein, carbohydrate, and fat make no difference. Life is extended and health is enhanced. Beyond that simple fact, we have an embarrassment of possibilities. The mechanism of CR can be interpreted according to most of the current theories of aging:
• CR increases the ability of the body to repair damaged DNA,
• Definitely decreases oxidative (free radical) damage in the body,
• Increases the levels of certain protective/repair proteins that respond to stress,
• Improves glucose-insulin metabolism,
• Delays age-related immunological decline as shown by virtually all immune functional tests.
CR is the strongest cancer-preventive technique known, although it's important to point out that disease prevention is a side effect of CR, and not the primary reason for the age-retardation or life span increase.
Dr. Richard Weindruch and I postulated some years ago that the mechanism is related to an increase in "metabolic efficiency." This can be thought of as leading to less "friction" in the body's generation of energy. Others have referred to this concept as "improved glucose fuel use." From the standpoint of evolutionary theory -- another approach to understanding the mechanism -- it has been proposed that CR kicks into play an "adaptive response." This response allows animals, faced by episodic periods of food shortage in the wild, to shift more of their metabolic energy into maintenance and repair, and so outlive or survive the period of deprivation.
In the one closely monitored human study (inside Biosphere 2 for two years), CR sharply lowered blood cholesterol (by up to 35 percent), blood sugar and blood insulin (by 15 to 20 percent), blood pressure (20 percent or more), and induced other changes paralleling those seen in CR rodents and (more recently) monkeys.
Human Application
Will CR retard aging (and do all the other wonderful things it does in lower animals) in primates, including humans? My answer is, "It almost certainly will." I say "almost" because it has not been applied in either monkey or human studies long enough to allow the demonstration of a change in maximum life span. Monkey studies will answer this first, and they are ongoing in three different laboratories (University of Wisconsin, University of Maryland, and the National Institute on Aging). It may be 10 to 12 years before we have unequivocal results. (Monkeys live a long time, although not as long as humans.)
So much for the "almost." The "certainly" in my answer is because (a) as so far tested, CR works across the whole animal kingdom, so it would indeed be surprising if it did not work in humans, and (b) studies on monkeys in the above three laboratories, and by me on the humans secluded for two years inside Biosphere 2, show quite clearly that the extensive physiologic and biochemical changes seen in CR rodents are also found in CR primates, including humans.
See one day in the life of a calorie restricted diet...
# For more information about the calorie restricted diet and Roy Walford, visit his Web site.
Can I get a grant to determine why there are only 8 buns in a bag but 10 hot dogs in a package?
Zone Perfect people
probably have a leg up.
They get good balance...
On the other hand, my parents are both in their mid-nineties and just now beginning to have problems living alone. They did it the old fashioned way -- by having long-lived ancestors. My father was a smoker for over twenty years, and quite a bit overweight by official standards. He was active, but never did anything just for "exercise". Neither has ever been on any of the fad diets -- low fat, low cholesterol, etc.
Besides that. I have to just hold out till about 100 (2070)by then anti agathics shuold be available or some form of nanotech rejuventation.
And spend a third of your life on the toilet, so it averages out the same anyway...
For those who have cancer or loved ones that do, please eliminate sugar from the diet, which only feeds the cancer cells and keep them alive and happy...Cancer loves sugar.
sw
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