This article appears in the June, 1996 issue Life Extension Magazine. The magazine is a publication of the Life Extension Foundation, a non-profit membership organization dedicated to the extension of the healthy human lifespan. For information: Life Extension Foundation
Dr. Walford has worked in several different areas of aging research. He is one of the few gerontologists who unabashedly endorses the desirability of extending the healthy human lifespan, and whose work has contributed mightily towards that goal.
The name Roy Walford conjures up images of laboratory mice who remain thin, healthy, and athletic at ages that ordinary mice can only dream of. This is the Walford ideal-- an extended healthy lifespan of vigor and vitality through a high-nutrient, low-calorie diet. His mice do it. Can we? And should we?
Some of the answers to those questions were revealed during Walford's stay in Biosphere 2, where he and seven others spent two years in a miniature world that was complete with an ocean, atmosphere, vegetation, and insects. Separated from the outside world, Walford and his cohorts went through the same experimental regimen that he forces his mice to go through. They consumed a nutritious, low-calorie diet that Walford is convinced could catapult us all into the next century.
Walford came out of the two years of enormous labor and stress that characterized the first Biosphere-2 "mission" with an injured back, a great deal of scientific data, a lot of material for art projects, and, except for his injury, the general good health that bolstered his conviction that his mouse studies would translate to humans.
Everyone knows that thin is healthy and fat is not. Every book-store sells low-calorie, low-fat, live-longer diet books. But Dr. Walford's plan does much more than that. Conventional diet plans sometimes claim that they help to prevent heart disease, stroke and cancer - the big killers. Dr. Walford's program, on the other hand, knocks out the big killers as a mere side effect of its ability to slow down the aging process. His aim is to extend life well beyond the point that most people succumb to these late-life diseases, and to keep people healthy and vigorous throughout those extended years.
Does it work? If having "young" biochemistry is evidence of aging retardation, then the answer is "yes". If having the physique, mind and energy of a man half his age, cholesterol of 140, and youthful skin - as Roy Walford does at age 71 - is any indication, then the answer is "yes". What does this legendary scientist, whose search for the truth led him to experiment on himself, and who once went off his diet in order to be his own control, have to say about longevity in the future?
LE: What's the maximum lifespan of humans?
RW: I guess it's between 110 and 120. There's one French woman who is authentically 120. If you started calorie restriction early in life, I think the survival curve could be greatly extended to 140, 150, 160, depending on how closely the animal work applies to humans.
LE: The quest for immortality has been plagued with charlatans. Why is that?
RW: All medicine has been plagued by charlatans. The thing that separates me, and others like me, from the charlatans of the world is, to put is simply, my curriculum vitae. My work is published in established journals, and judged by the scientific community to be acceptable research. It is not quite that simple, of course, because there is doubtless good work in the category of "alternative medicine" that doesn't get published in all the regular journals.
LE: Have you done any studies on calorie restriction in monkeys?
RW:That's being done by Richard Weindruch and co-workers at the University of Wisconsin, George Roth and co-workers at the National Institute On Aging, and researchers at the University of Maryland.
LE: How well do humans follow the animal data?
RW: So far humans, monkeys and rodents test pretty much identically regarding physiologic function. The biomarkers of aging are changed by calorie restriction, and rodents and humans show the same changes. We haven't tested everything yet, but we have tested a number of hormones, cholesterol, blood sugar, insulin, glycogen...things like that.
LE: What was Biosphere all about?
RW: The Biosphere is a closed ecological space near Tucson, Arizona that was set up to be an ecological laboratory and to serve as a prototype space station. I was the only physician inside for two years.
LE: What did the Biosphere teach you about calorie restriction?
RW: We were all on a very low calorie, nutrient-dense diet, the same kind of diet that the rodents get. Everybody lost a lot of weight and showed the same physiologic changes that long-lived rodents do on such a diet.
LE: Biosphere was too short of an experiment (two years) to determine whether calorie restriction increases lifespan in humans, wasn't it?
RW: It was too short to measure its effects on lifespan and disease, but it was long enough to show that the biochemical changes which occur in human dietary restriction are the same as those occurring in rodents - great decreases in blood sugar, cholesterol, insulin, T3 (thyroid), a mild increase in cortisol and other changes.
LE: How many calories did you consume?
RW: About 1,800.
LE: Were you hungry?
RW: Somewhat hungry, but not uncomfortable or famished. It's not a "starvation diet". That's nonsense. If a person eats food that is nutritionally sound, they will eat fewer calories and still feel satiated.
LE: Does it make a difference whether a person restricts fat, carbohydrates, or protein? RW: Anyway you do it, it will work, as long as you don't get into nutrient deficiency. As long as the calories are low and there's enough vitamins and minerals so there's no deficiency, you'll extend lifespan, regardless of the distribution between carbohydrates, proteins, and fat. You cannot, however, just eat less of a junk diet and extend lifespan. It has to be nutrient dense.
LE: I've notices that kids are becoming sexually mature at earlier ages. Even babies are big for their age compared to, say, 20 years ago. What's going on?
RW: They're overeating.
LE: What is that doing to their future?
RW: Overeating shortens lifespan and increases incidence of disease. Dr. Morris Ross once kept a strain of rats on four different nutritional programs: 10%, 25%, or 40% protein. The fourth group could rotate and pick whatever diet they wanted. What happened with the group that had free choice is that they grew more rapidly, reached sexual maturity at a younger age and had more babies, but died sooner, and had a much higher incidence of tumors.
LE: Why is this?
RW: Very likely because we're programmed by natural selection to make food selections for early maturity. In other words, nature has programmed men and women to make choices that cause them to reach maturity as soon as possible and have as many babies as possible. It's good for species survival, so it gets "selected" by evolution; but it's not good for individual survival.
LE: What about disease? How does it fit into the picture?
RW: Nature doesn't care much about the "diseases of aging" because those diseases come on late in life when you're not productive anymore in terms of children.
LE: So what you're saying is that if we want to live longer, we have to thwart our evolutionary destiny to procreate, then die, so to speak.
RW: In a manner of speaking, yes, but that doesn't mean you can't be sexy.
LE: What can the average adult do from this point in his or her life to extend lifespan?
RW: They can adapt to a high quality diet. That's the first step. The next step is to eat less. Don't eat empty calories. The third step is exercise, but that's less important than diet and perhaps somewhat equivocal in terms of actual aging.
LE: Can I exercise my calories away and extend my life that way?
LE: Why not?
RW: Experiments in animals indicate it does not work. Exercise does three things that at least on the surface would seem are contradictory to longevity: it raises metabolic rate, and creates free radicals. But it does have health benefits in terms of disease, so the overall effect is good if you do it right.
LE: Can skinny people expect to live longer by virtue of being thin?
RW: I think they can a bit, but not to the extent you can on calorie restriction. There's a paper out in the recent New England Journal of Medicine by Manson and co-workers, as part of the so-called "Nurses Health Study" where they studies 115,000 women. Basically they found that the skinnier you are, the longer you live, as long as the skinniness from smoking or undiagnosed disease and such is factored out. When these are factored out, there seems to be no lower limit.
LE: Besides avoiding obesity-related diseases, what accounts for this finding?
RW: I'm not sure, actually. Are they thin genetically, or are they thin because they don't eat very much? Probably both, and it's a subgroup of the latter cohort that influences the statistics in favor of an association between thinness and longevity.
LE: What about metabolic rates? There is a popular perception that thin people have high metabolic rates.
RW: I don't know about metabolic rate and actual lifespan, but calorie-restricted animals have a lower temperature, about one degree lower. Animals with lower body temperatures like fish and lizards live longer at a lower temperature. Their body temperature is the same as their environment, so this can be easily studied. We established this a long time ago in studies with the so-called annual fish.
LE: There is a recent study showing that melatonin lowers body temperature in women.
RW: That ought to be beneficial then.
LE: Melatonin is the hottest anti-aging therapy. What do you think about it?
RW: I haven't looked into it in depth. I don't know offhand of any studies where melatonin has been given to long-lived strains of animals.
LE: Why haven't the studies been done?
RW: It takes a big effort and you don't get much credit for it scientifically.
LE: Maximum Lifespan was written a little over 10 years ago. What has occurred in the last 10 years regarding the theories discussed in the book?
RW: There have been a lot of general advances in the theories of aging. There have been all kinds of new ideas about it. I think there's more evidence that the major histocompatibility complex influences aging. (Note: the MHC is a group of genes that codes for components of the immune system.) There is certainly a lot more evidence now that calorie restriction works in primates, including humans. I don't think any of the theories outlined in the book have been disproved. The same theories are still contending, but in a much more extended field of information.
LE: What are you currently working on in your lab at UCLA?
RW: Besides the calorie restriction model, and the aging of T-cells (a form of white blood cell) in culture, we're working on the genetics of aging. We think that some of the genes of the MHC regulate aging.
LE: You've referred to the MHC as being the "key gene system of aging".
RW: Well, I would say one of the most important gene systems in aging. So recently we've taken certain MHC genes from a long lived species of rodent and put them into ordinary lab mice.
LE: What happened?
RW: We don't know yet. We've got it all set up and we're looking at a lifespan and reproductive senescence, and other parameters.
LE: What are you looking for?
RW: The first thing is to see whether they have a longer lifespan. The next thing is to ask why.
LE: If it works, then what?
RW: If any of these strains of transgenic mice live longer, then we've proven that the MHC influences aging. this is the main experiment, to do that. We have a lot of evidence that it will, but it's all what I call "plausibility evidence". That's not quite good enough.
LE: What have you learned so far about MHC and aging?
RW: That the MHC influences DNA repair, the level of free-radical scavengers, the level of the mixed-function oxidase system, and the immune response. So if it has an influence on all of those, it ought to have an influence on aging. It's a plausibility argument. Now we have to prove it by doing what is the crucial test of any and all aging theories; influence the maximum life span of a long-lived strain.
LE: And then what?
RW: Then, if that works, we have to figure out why and what that particular gene or gene combination is doing in terms of the machinery of the body.
LE: One of the biggest criticisms of calorie restriction as a method of life extension is that people will have to walk around hungry all the time. What do you have to say about this criticism?
RW: You don't have to walk around hungry. If you change the quality of what you eat, you can be satisfied with lower calories. There have been experiments in both people and rats that if you give them the so-called "cafeteria duet" - a junky American diet - and let them eat as much as they want, they will eat about 3,000 calories. If you take the same people and give them a high-quality diet, and let them eat as much as they want, they'll settle for about 2,500 calories. So right off, you can knock off 500-600 calories just by eating better food.
LE: You talk about malnutrition versus undernutrition. What is a nutritious diet?
RW: A diet that has a lot of nutrient value per calorie, and at least equal the RDA's for all the essentials.
LE: What does "nutrient" mean when you say it? What do you think about megadoses of vitamins?
RW: People should get the RDA's and doubtless more of some nutrients. There's less evidence for actual meagdoses. There is a huge amount of evidence that if you eat a low-calorie diet and you're not deficient in anything, you will extend lifespan. There's's fifty years of evidence in animals, and about five years in monkeys and humans, so it's very strong.
There isn't that kind of evidence yet for megadoses. It's largely what I call plausibility evidence. The evidence shows that taking antioxidants extends mean lifespan and helps to prevent diseases, but the only studies yet published with antioxidants showing extension of maximum lifespan were in short-lived strains of animals.
That's certainly OK, but could just mean cure of disease, not slowing of basic aging. In my view, you have to do the crucial test for antioxidants, melatonin, DHEA, growth hormone, and so forth. So far, only calorie restriction has really passed this test.
LE: I've read that sudden and severe calorie restriction can be dangerous.
RW: Certainly people should embark on dietary restriction gradually. When we originally looked at the animal data on calorie restriction, we found that previous researchers had not been able to extend lifespan by using calorie restriction beginning in adulthood. But when we looked over their experiments, we found that they'd initiated the calorie restriction regimen quickly...over a week or so and it didn't work. We found that if we did it slowly, over two or three months (in mice), that it would extend lifespan. So yes, it should be done very gradually.
LE: How does a person determine how many calories they should cut out?
RW: By weight. They should determine their "set-point" and then restrict calories enough to take off 10-25% of their weight. Ten percent is not difficult, 25% is more difficult. But it's mainly a mind-set. Some people can do it very easily, some people have a great deal of trouble. But people can do it.
(Note: The set-point to aim for is your weight when you were 20-30 years old. Whatever calories maintain a person 10-25% below this weight is the number of calories you should be eating on the calorie-restricted diet plan).
LE: You and your daughter Lisa Walford have developed a computer program to revolutionize the way people eat. I've used it and I think it's great. What can your diet planner do for people?
RW: Well, if they want to go on a calorie restriction program, that's the best way to do it. It's quite difficult to set up daily food combinations which are both low in calories but supply all the RDA's just by looking at tables of food values. My diet planner has the only adequate "search" program to achieve optimal nutrition with calorie restriction. The data base is one of the best.
Incidentally, there is a lot of confusion when people look at the data bases that go with the various nutrition programs. They think a program with a data base of 6,000 or 7,000 foods is better than one with 4,000, but that's not necessarily the case.
RW: It's not how many foods you have, but how complete the data are for each food. I cover about 28 to 30 items, including amino acids, vitamins, minerals, calories, fat and so forth. A lot of programs cover maybe only 10 items...a few vitamins and a couple of minerals, that's it. But you can't get a nutrient dense diet if you don't know how ALL the nutrient values stack up.
LE: What else should people be aware of with regard to computer diet programs?
RW: Again, don't be fooled by claims for a big data base. You'll find that when you try to look up the data for certain foods, you'll find data for calories, carbohydrates, protein, fat, a couple of vitamins, and that's all. Try to look up say a Campbell's soup, for example, in the source books, and you'll find a lot of blanks.
The same is true for the majority of processed foods. You'll find about six items and then it's blank after bland in the data base. It's better to have a smaller data base that's more complete.
LE: How many foods are in Dr. Walford's Diet Planner?
RW: About 3,000. But the data are not complete for all those 3,000 items. My data base is simply the most complete available. And we've omitted foods for which the available data are too skimpy. One has to make a judgement weighing size and completeness. Really complete data are only available for about 300 foods, and that's not enough for most people to be willing to live on.
LE: What kind of information is available for each food?
RW: In the diet planner, vitamins, minerals, amino acids, fats, carbohydrates, protein, calories: all the usual stuff, but as complete as we can make it for each food.
LE: So, working with the interactive diet plan is the best way to get serious about what you eat.
RW: It's certainly the best way to create a nutrient-dense diet. The problem in developing a nutrient-dense diet is that you have to get maximum nutrients in a low-calorie bin. In computer language we call that a bin-packing problem. It's difficult to do this by just looking at tables. It takes forever to try to eyeball all those tables. You can do it easily with the diet planner because of the search program. You can select a bunch of foods you want to eat for the day, look at the nutrient value and say: "Well it looks pretty good, but it's still deficient in vitamin X and Y and mineral Z." You can also introduce constraints into the search, like "I want a list of foods high in X, Y, and Z, but at the same time low in fat." Or any other combination. The search program is the unique feature of the diet planner, which no other nutrition software program even approximates.
LE: When can we look forward to having total control over this evolutionary process which is doing us in?
RW: It depends on what you mean by "total", and I have to add that "prediction" is about the only thing more hazardous than overeating. With that caveat, I'll say that fairly soon we'll have some extension of lifespan by easier means than calorie restriction. However, the two may be additive in that calorie restriction plus prescription X will keep you alive longer and healthier than either alone.
LE: What for example, might prescription X be?
RW: Somebody might find a way to upregulate DNA repair. It could be tomorrow, it could be ten years from now. We can't predict it very well. My favorite story about predictions is from C.P. Snow of physics. Einstein, Rutherford and Niels Bohr - the three greatest physicists of the first half of this century - all predicted in 1935 that we would never get power from the atom. Ten or so years later, we got a lot of power from the atom bomb. In 1950, or about then, the government got a committee together to predict what would be the size of the computer industry in twenty years. And this distinguished committee predicted that, in 1970, there would be 100 main-frame computers.
Actually, there were 100,000 of them. The farther you get into the future, the less the experts are able to predict. I suspect it will be the same with the control of aging and lifespan extension.
So the best strategy in my view is to go with what we are rather confident works now, which means calorie restriction and add other things to that if and when they come along and are shown to extend the maximum life span of long-lived strains of warm-blooded vertebrates like mice or rats.
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