Will CR Work in Humans?
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Will CR Work in Humans?
This is a very difficult question to answer with absolute certainty. The main problem is, of course, that the approach that would yield the most certain result -- doing an actual experiment and measuring only the most relevant endpoint, length of life -- could take over a century to complete! Were we in possession of thoroughly validated "biomarkers of aging" -- indices that measure the deterioration of the body as it ages, instead of clocking the mere passage of time -- then we wouldn't need to wait a century for the results of a human CR experiment to yield certain results. Instead, we could just measure the biomarkers of the experimental group, and see if they change more slowly than those of the group of people eating a normal diet. Unfortunately, while there is great interest among researchers in finding biomarkers that would suit such a purpose, none that fits the bill perfectly has yet been found. Many possibilities have been proposed, however, and are now being investigated and debated. Some of these are looking quite promising, and are probably sufficient for use in upcoming human CR experiments, as well as in the (non-human) primate studies which are now underway.
The evidence that bears on the question of the applicability of CR to humans then, is at present indirect. There is nonetheless a great deal of such indirect evidence, enough that we can say with an extremely high degree of confidence that CR will work in humans.
Until recent fairly hard data on primates and humans became available, most of the evidence that CR would work in humans was just this: CR experiments have been tried in many, many different species, and CR has been shown to work in all them, with a couple of odd and likely irrelevant exceptions (for example, the amoeba -- a species at an extreme evolutionary distance from homo sapiens -- becomes immortal if fed more than normal). Our beliefs about the efficacy or safety of other dietary regimens, and some drugs, come from studies performed on rodents alone, so there's no more reason to doubt the efficacy of CR for humans than there is to doubt the efficacy of these other diets or drugs. Bear in mind that CR has been successful in slowing aging in all higher organisms in which it's been attempted, which include many creatures other than rodents. I have not heard a good argument as to why the mechanisms whereby CR slows aging in all these creatures would have been "lost" by humans, or never would have evolved in our ancestral line.
In Roy Walford's first popular (geared towards laypeople) book devoted to CR, The 120-Year Diet, other arguments were made in favor of the applicability of CR to humans. Let me briefly mention the most interesting piece of data: Okinawans are the only large group of people who tend naturally to eat a diet approximating the high/low diet, though it is not as strict as it could be. They live much longer than genetically similar people on the other Japanese islands, who do not eat a high/low diet. It's not easy to see what other than CR could explain this difference in longevity.
The above conjectures were enough to convince me, and many others, that it would be foolish for someone who wants to live a long life not to practice CR (or not to try, at least, to practice CR). But recently, two things have greatly strengthened the case that CR will work in humans. One is the primate CR studies that have just begun to yield data, and the other is the "unintentional" experiment on humans that Roy Walford was able to perform.
Most of the researchers who remain skeptical that CR will slow aging in humans agree that if CR works in non-human primates, it will most likely work in humans. This is because monkeys are nearly identical to humans, genetically. Because the monkeys being studied have much longer life spans than rodents (true even of the relatively short- lived squirrel monkeys), it will be at least another decade before actual life spans between the experimental and control groups can begin to be compared, but the initial results suggest that the CR animals are aging at a slower rate. For example, one study has shown that puberty has been delayed in the monkeys in which CR was instituted at a young age. In addition, virtually all of the changes that are seen in CR rodents are being seen in the monkeys (again, it still a bit too early to know for sure in the case of some of these changes, but we'll probably know within a year or two -- though of course we'll still have to wait for the "hard" data of mortality).
As Roy Walford has put it, "for CR not to work in humans [or in other primates], all of our theories of aging would have to be wrong" (I'm paraphrasing). The idea here is, even though we don't have actual mortality data in the monkey studies or human studies, the changes seen in the monkeys -- changes in glucose metabolism, changes in anti-oxidant defenses, etc. -- are changes that, if our theories of aging are correct, would have to result in a slowed rate of aging. Again, this doesn't yield perfect certainty, since the theories could be wrong. But it seems unlikely that all, or even most of the theories, are totally wrong.
The objection might be raised that, although monkeys are nearly identical to humans genetically, they still don't live nearly as long as humans do, and thus the applicability of the monkey studies to humans may not be justified. As it happens, a situation arose accidentally in which a group of people were forced to do CR. This situation came about in the Biosphere 2 project. Again based on the results of this "experiment," we would have to conclude that CR will slow aging in humans, unless several of the leading theories of aging turn out to be completely wrong: the changes in fasting glucose levels and immunity seen in these people would most likely mean that they were aging more slowly. (See Walford, Harris and Gunion, 1992, and Walford and Walford, 1994, for details.)
"But I Thought Heavier People Live longer than Skinny People?!!"
(See main article, Relation Between Body Weight and Mortality and Morbidity)
Some data began to make the rounds ten or fifteen years ago which appeared to show that thinner people died earlier than slightly overweight people or even people of average weight. Indeed, some people calling themselves researchers still make this claim without any qualifications. The data on which this claim has been made has nothing to do with CR. First, there are several problems w/the data itself. Two (of many) examples: 1) the compilers of the data in the initial studies didn't, with one exception of which I'm aware, control for smoking (people usually gain weight when they quit smoking, but they tend to increase their longevity since they aren't as much at risk for lung cancer); 2) none of the studies has controlled for -- nor could easily control for -- the numerous, often subclinical disease processes such as inflammatory bowel disease, celiac sprue, etc., which have thinness as a side-effect. People with these illnesses might die earlier, and weigh less, but they're not dying early because they ate a high/low diet. Astonishingly, at least some branches of the US government still promulgate empirically invalid body weight guidelines saying not merely that it isn't healthy to be thin, but that gaining weight with age is good for you. The Journal of the American Medical Association (JAMA) has published a number of articles recently -- which can be read on-line by registering (for free) with the AMA Web site -- which call into question these guidelines. The most widely noted of these (not on the AMA Web site) is the article by Walter Willett, of the Harvard School of Public Health 3. Officials at the USDA are beginning to modify the official ideal weight guidelines for Americans, but they have still not gone nearly far enough.
Secondly, the point of CR isn't to be thin, it's to eat less, and to eat less in a specific way. Overweight people are under social pressure to be thin, so they may be more likely to eat less than skinny people, who often can eat as much as they want w/o gaining weight. So even if heavier people DID live longer than thin, healthy non-smokers, it wouldn't constitute evidence against CR's applicability to humans.
Finally, it's conceivable that some people who are thin are thin as a result of their eating less of a poor quality diet. This makes them "nutritionally analogous" to many people in the developing world, instead of being analogous to Okinawans, the only relatively large group in the world that "naturally" follows a high/low diet. Someone eating a diet of the same quality as the thin person eating the junkfood diet, but in greater quantities, might be able to overcome shortages in vitamins and minerals simply by virtue of the huge amount of food they're eating, even if it is junkfood. Thus, while the non-restricted junkfood-eating person (a person following a "high/high" diet or "sufficiently-high/high" diet) isn't getting any CR benefits, s/he is less likely to be short on vitamins and minerals, which might prevent certain types of early death suffered by someone eating the "low/low" diet.
Conclusion to the Question of Whether CR Will Work in Humans
In short, the evidence is, in my view, overwhelming that CR will slow aging significantly in humans, probably to the same degree -- as measured by percentage of added years -- seen in the rodent studies. This could mean a gain of up to thirty years; and, if you are prone to any of the many diseases that CR can prevent or help prevent, such as heart disease or adult-onset diabetes, the gain might be far more than thirty years. Remember that the "40% gain" figure mentioned in connection with the rodent studies is a gain in maximum life span, this reflects an alteration in the rate of aging, and does not take into account all disease- prevention (though the line between disease-prevention and aging- retardation is a fine one, in the case of many diseases).
For me, and for most people who practice CR, or who are seriously contemplating practicing CR, the main questions are not whether CR will work in humans, but rather: 1) Is it possible that something better than CR -- something capable of slowing and reversing aging -- will come along soon enough that we don't have to do CR, but can just wait until the better method comes along? and 2) How can we deal with the hunger...? These questions are beyond the scope of this FAQ, though I will offer a few brief thoughts below. The Anti-Aging Plan: Strategies and Recipes for Extending Your Healthy Years of Life (Walford and Walford, 1994) has some excellent ideas on why a high/low diet might not leave one feeling as hungry as one might think.
Note: Future Research
For people still skeptical about CR's potential to work in humans, I would suggest keeping an eye on three things:
- The ongoing primate CR studies. Within a year or two, there should be much more significant data from these studies.
- The upcoming major human CR study/ies (footnote 2). The initial data from the primate studies has been so encouraging, that several human CR experiments are being planned. One is now underway. The members of the CR Society who practice more than mild CR will themselves likely be part of a peer-reviewed article soon. Jordan Sparks, a member of the group, conducted a brief, informal survey of some of the members of the list. It gives some idea of the range of body-weight changes people on different degrees of CR experience.
- Other anti-aging strategies. There's no point in doing CR if an easier and better (or as good) strategy exists. (Actually, some people might like being very lean -- it has its advantages.)
The only currently available candidate that looks like it stands a chance of turning out to be as effective as CR is melatonin-replacement therapy. (DHEA does not look as promising, and other hormone-replacements need much more work.) Drop by a medical library from time to time to check on the status of the melatonin research. (And read Sci.life-extension -- with a skeptical eye, of course....)
Notes
Footnote 2. Kelsey, Tim "How to Live to 140," The Sunday Times, 1996 January 14. (To follow other links at the Times Web Site, you may need to register (for free) first.) This is a short, pop article about CR which gives a bit of info on the human CR studies now (January, 1996) underway. (Note, Jan. 21, 1996: Hmm.... It appears the Times cans articles in the Sunday paper as soon as the next edition is put out. I'll work on making a copy of the article available. I've emailed the Times twice asking permission to get a copy of the article, but they're not responding. Maybe they're still grappling with copyright issues. You want to email them yourself to suggest that they make past articles available, including the article on CR.)
