HOW THE LONGEVITY DIET MAY EXTEND YOUR YEARS

Let us think about what the extrapolated graph might mean in concrete terms. First, keep in mind that no health regimen is perfect. Some people have extraordinarily bad genes, or will simply have extraordinarily bad luck while crossing a street—accidents happen.

But CR (calorie restriction), started early in life, can be expected to prevent many unusually early deaths. In our extrapolated graph, we see a dip in the non-CR group very early on, when the subjects are in their teens and twenties, and the dip continues downward, though still very slowly, when they move to their next decade or so of life. If you had a group of fifty or so people, that might be just what you’d expect: you’d see maybe one or two very early deaths, as in the situation with which many of us are familiar, of a schoolmate dying of cancer or in a car crash—a rare yet nonetheless statistically expected phenomenon. As we move into the next age group, people in their thirties and early forties, another death we would still consider quite premature might be that of someone we know who has bad genes for cholesterol production and who dies of a heart attack in his late thirties, although deaths by heart attack after two score years are, unfortunately, not at all uncommon, especially among men in the United States.

Animal studies have shown that CR radically alters biomarkers associated with heart disease. Here, when it comes to humans, we have more than epidemiological data. We also have much direct evidence from human studies, such as Professor Walford’s Biosphere 2 data, and, more recently, the ongoing study at Washington University in St. Louis, to name just two. Such studies have shown that people with the healthy cholesterol levels that result from CR have a much, much lower risk of cardiovascular disease. Thus, the person in the non-CR group who dies of a heart attack at age forty or so would very likely live much longer—perhaps an additional two or three or even more decades—on even a relatively mild CR program.
We know also that CR dramatically reduces the incidence of cancer in laboratory animals, and evidence has been mounting that CR, not surprisingly, reduces cancer risk in humans as well. Thus, it’s not at all unrealistic to suppose that CR, whether mild or severe, may prevent early deaths from cancer, or may at least radically push it back, as suggested by the extrapolated graph for human life expectancy.

As we follow our extrapolated graph over to the right, we see many more people in the non-CR group dying in their fifties and early sixties—and even a few in the mild CR group, as well, bearing out animal-study results that CR in its milder forms is not nearly as beneficial as a more stringent program. Once we get to the age of sixty-five or seventy, people in the non-CR group begin to dwindle dramatically, as disease strikes or organs fail. If human life expectancy indeed follows that of animals placed on a CR diet, we would expect the threshold of what we now consider elderly to be pushed back nearly fifteen years for the group of people on the mild CR regimen, and that it would be pushed back even more for the subjects on rigorous CR.

And, as we move even further to the right on the timeline, we see that very few of the non-CR group are likely to be alive in their nineties. However, most of the mild-CR group will still be around then, as will the vast majority of the rigorous CR groups.

So what, then, is the ultimate effect of CR? Calorie restriction shifts the survival curve to the right, and it does so in such a way that everything is pushed to the right. People on CR will not become senile and crippled at the same age as others, and then be forced to live an extra few decades in this state of decrepitude. Quite the contrary; CR promises that youthfulness itself will be preserved. Thus, for the group on more rigorous CR programs, the cycle of life and death would look very different indeed from what we picture as the normal life cycle. If you go on even a moderate CR program, you can expect to live, on average, at least a decade longer than you otherwise would—and perhaps several decades longer, if cancer or a stroke is averted. And it’s not just that your life span is extended, your youth span will also be extended. Aged laboratory rats and mice on CR run mazes just as quickly and intelligently as they did when they were in the equivalent of their “teens.” They also have sex at an age when the animals in their studies’ control group—those creatures that, given the mortality of non-CR rodents, are lucky enough still to be alive—don’t even remember what sex is.

From the Lab to Your Life: CR Research Through the Ages

Prehistory 

The notion that restricting one’s diet could be salubrious in various ways is actually an ancient one. In the Middle Ages, for example, it was thought that tumors could be eliminated via restricted eating: Both the tumor and the body need food to thrive, but the body, being more virtuous, would survive a reduction in food longer than a malignant—and therefore evil—tumor, and thus the tumor would die before the body would. (Do not try this at home!)
So went the reasoning. At the beginning of the last century, a slightly more biologically enlightened version of this line of thought led to some scientific studies revealing a correlation between food consumption and tumor growth. As early as 1909, for example, it was shown by Carlo Moreschi, an Italian immunology researcher, that tumors transplanted into underfed mice did not grow as quickly as tumors transplanted into normally fed mice. Over the next ten or so years, the development of tumors itself was shown to be to suppressed in underfed lab rodents.

Although it is true that most types of cancer become more prevalent with age, establishing a relation between cancer growth and food intake is not the same as establishing a relation between rate of
aging and food intake. That latter relationship only began to be explored two decades later, and even then partly as an unintended consequence of a Cornell University cancer researcher’s experiment.

The Modern Period of CR Research 

Clive McCay, a researcher at Cornell University, was interested in the long-term effects of stunted growth upon mice, which in a study in the mid-1930s he induced via a drastic reduction in the lab animals’ food intake. A completely unexpected finding was that the rodents lived around a third longer than rodents on a normal lab diet! No one knew what to make of this finding, though some researchers tried to figure out what the crucial factor was—a particular component of the diet, or the mere quantity of food, or the total energy content of the laboratory meals. It was shown in the 1940s that it was indeed the energy content—which is to say, the caloric content—alone that made the difference. Indeed, by reducing the energy content only, and not any other components of the diet (such as critical vitamins and minerals), the benefits were even greater.

Despite that important breakthrough, little CR research was done until the 1970s, when the modern period of research into this regimen began. Knowledge of molecular biology had developed to the point where it was possible to investigate how CR exerted its effect. Over the next decades, CR research evolved into the standard, primary tool for investigating the fundamental mechanisms of aging, because it quickly emerged that calorie restriction is the only intervention that retards the rate at which organisms age. Understanding how and under what conditions CR works in laboratory animals has thus been viewed as tantamount to understanding the aging process itself. And because no other reproducible and verified means of appreciably slowing the aging process has yet been discovered, CR has, since the 1970s, remained the primary laboratory model for understanding the mechanism, or more likely mechanisms, of aging in laboratory animals.

The general research strategy is not complicated or overly technical. One approach is the following: A researcher first selects one of the myriad differences between CR animals and normally fed animals. He or she then tries to elicit the one change, be it a hormone that is expressed at a higher or lower level in CR animals, or even a particular gene whose function is not yet known, which is expressed at a different level in animals on CR. Then, the researcher tries to see whether the alteration of this one factor in normally fed animals can elicit the CR effect, or, conversely, whether an attempt to suppress this change in animals on CR might abolish the CR effect. For example, animals on CR typically have lower body temperatures than do their non-CR control group. Professor Roy Walford, along with some Japanese colleagues, showed that artificially raising the body temperature of animals on CR abolished at least certain aspects of the CR effect. This suggested that this one change, a lowered body temperature, might be fundamental to the beneficial effects of the diet. The next step would be to see what happens when we lower body temperature in animals not on CR. Interestingly, tentative research results show that lowering body temperature can indeed increase longevity somewhat, though not as much as strict CR.

The most recent CR studies follow this same pattern, and scientists appear to be getting very close to understanding how CR works. Research at Brown University, Harvard University, and MIT has shown that forced expression of a particular gene can actually elicit the CR effect, or at least aspects of the CR effect, in yeast and fruit flies. This change in gene expression, more than hormones or body temperature, appears to be an essential factor, if not the essential factor, in the host of changes that lead to the greatly improved health seen in laboratory animals on CR. For more about this exciting new research.

For now, let us summarize what we know about the consequences of CR in laboratory animals:

How CR Affects Your Health
CR produces a wide variety of positive effects upon laboratory animals. Many of these benefits have actually been confirmed, in short-term studies, in humans as well.

Improved Insulin Sensitivity
Insulin is a hormone secreted by the pancreas that enables your cells to use their most important fuel, glucose. As we age, cells tend to become less responsive to insulin. This leads to unnecessarily high levels of glucose, which can lead to type 2 diabetes, and maybe even accelerated aging.

The effect of CR in lab animals on insulin sensitivity is one of the most well-documented CR research findings. One of Professor Walford’s contemporaries, Edward J. Masoro, of the University of Texas Health Science Center in San Antonio, was one of the first to investigate the mechanism of the dramatic effect of CR on the age-associated decrease in insulin sensitivity. Many others have expanded on this work.

The data from the long-term studies of CR in nonhuman primates have been consistent with the findings in rodents. In the NIA (National Institute on Aging) Primate Study, the monkeys on CR have dramatically lower circulating insulin levels, which we know is an excellent measure of insulin sensitivity. (The more sensitive your cells are to insulin, the less your body needs to secrete insulin into the blood.)

And countless studies of short-term CR in overweight humans have shown conclusively that insulin sensitivity increases on CR.

Although we don’t yet have long-term data on CR in people who are thin to begin with, those who already have type 2 diabetes can probably even improve their glucose metabolism with CR. The American Diabetes Association has begun stressing that reducing energy intake, as part of a comprehensive program of diabetes management, can improve insulin resistance in diabetics.

Even a conservative physician with no awareness of CR would agree that CR will most likely reduce your chances of developing type 2 diabetes, and, if you already are “prediabetic,” CR will probably halt the march toward full-blown diabetes.

Lower Average Circulating Levels of Glucose 
This change is, of course, directly connected to insulin sensitivity. The rodent studies show lowered levels of circulating glucose, just as they show lowered levels of circulating insulin, since the two go hand in hand. But in addition to being correlated with lowered insulin, a lowered glucose level is a good thing in and of itself.

Glucose is your body’s primary liquid fuel. Like your car’s gasoline, it is an “energetic” chemical that can damage what it comes into contact with (see chapter 4 for more about this effect of glucose). In brief, superfluous glucose will needlessly harm the molecules, cells, and tissues of your body. According to many theories of aging, this damage may well be a significant cause of aging. Thus, all your tissues, from brain tissue to skin tissue, will benefit from lower levels of circulating glucose in your blood: just enough to keep your body running smoothly, without “spills.”

Increased Maintenance of DNA 
DNA (deoxyribonucleic acid) is the extremely long, intricate, fragile molecule that constitutes your body’s blueprint. The design specs encoded in your DNA determine most of your biological characteristics as you grow into an adult, but they also guide ongoing repair and maintenance during your many (we hope!) decades of adult life. As we age our DNA becomes damaged, and not all of that damage can be repaired. This deterioration of your DNA slowly results in progressively worse functionality at all levels: your cells, organs, and your whole body.

The earliest studies of CR in laboratory animals could not measure the ability of CR to protect DNA against age-associated damage, since DNA hadn’t even been discovered yet! But starting in the mid-1980s and early 1990s, new techniques made it possible to show
that DNA damage is reduced in laboratory animals on CR, although, not surprisingly, the effect is greater on DNA involved in the use of energy. Interestingly, it isn’t simply that DNA damage is reduced. There is an actual increase in DNA repair.

Studies of the effect of CR on DNA damage in humans are ongoing, though even now, in 2010, we have substantial evidence that CR in humans reduces DNA damage. In addition, although studies on the reduction of obesity are not the same as CR studies in the non-obese, it is worth noting that several weight-loss studies have shown that telomere length of at least some cells increases when the obese go on a calorically restricted diet. Telomeres are the “caps” on the ends of DNA strands. When these caps get too short, the DNA strands become unstable.

Whether or not damage to DNA has anything to do with aging per se, keeping your DNA stable and intact is a good survival strategy! Changes in cellular DNA are implicated in many diseases, above all cancer.

Reduction in Expression of Oncogenes 
On a CR regimen, you can expect that oncogenes—genes that lead to abnormal, unnecessary cell proliferation (which is all cancer really is)—will be less likely to be “switched on.” This effect is very well established in laboratory mice.

There is considerable epidemiological evidence that CR in humans reduces cancer risk, and, amazingly enough, there is even evidence that mere “FR”—indiscriminate restriction of food, not a targeted restriction of calories in an otherwise healthy diet—reduces cancer risk.30 Thus, when a proper CR program is instituted, we might expect an even greater reduction in risk of cancer.

Reduced Decline in Sexual Activity with Age
The sexual activity of laboratory animals on an extreme CR regimen actually decreases a bit in their younger years. This is consistent with theories of why CR would have evolved in the first place: Resources get shifted away from reproduction and growth, and moved toward repair and maintenance. But in animals on CR, sexuality does not decrease with age at the same rate as it does in their control group. In fact, this was first noted over fifty years ago in studies by Maurice B. Visscher at the University of Minnesota.

As Professor Walford noted in Maximum Life Span, there are astonishing studies showing that laboratory animals on CR not only still have sex and otherwise display sexual interest at an age beyond that of animals in the non-CR group that have died, but they can actually become pregnant and give birth to healthy babies when all of the control animals are dead!

Moreover, CR actually increases follicular reserves—meaning, in human terms, that menopause could be postponed by many years.

Lowered Blood Pressure
This is of course good news for those of you who are worried about stroke or embolisms. This is also, by the way, something you can easily measure yourself at one of those blood pressure machines that many pharmacies and health-fair clinics provide for public use. Take advantage of these services. Again, hard evidence of your progress will increase your motivation.

Reduced Risk of Arthritis 
Arthritis may not be life threatening—at least not while you’re still in midlife—but it is extremely painful and restrictive. We know several artists and musicians who, only in their forties and fifties, will soon have to stop practicing their art because of this condition. In the lab, CR has been demonstrated to greatly delay the onset of arthritis.

Improved Mental Functioning 
This is a lab finding that is perhaps most important to keep in mind if you’re worried about CR simply prolonging the decrepit phase of old age. It most certainly does not—it prolongs and even restores youth, in many ways. That a mouse which in human years would be over one hundred years old can zip through a maze with the problem-solving skills of a young adult rodent may seem incredible, but this phenomenon has been documented repeatedly in research studies. The ability of calorie restriction to maintain youthful mental functioning is believed to be the beneficial result of a very straightforward effect already discussed: because it strengthens and repairs the body’s cells in general, CR prevents the brain cell death that normally occurs with age.


By Brian M. Delaney and Lisa Walford in "The Longevity Diet", Da Capo Press (member of the Perseus Book Group), USA, 2010. Adapted and illustrated to be posted by Leopoldo Costa.

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