Considering a Negative Result for Primate Calorie Restriction

As I'm sure you noticed, the latest data from one of the two long-running primate studies of calorie restriction is being presented in the press as a negative result: no extension of mean life span in the rhesus monkeys in that study. This contrasts with another study that may or may not presently show a modest extension of primate life span with calorie restriction, depending on how you feel about the way in which the researchers are interpreting their data.

The press are largely running with "calorie restriction doesn't work," but that's because the mainstream media is shallow, either reprinting a superficial summary or at best treating each new research result in isolation rather than considering it in the context of the field as a whole. Doing the job properly, employing actual knowledge and analysis, takes more time and doesn't sell any more papers - so why bother? This is why the media should chiefly be used as a flagging mechanism; if you see discussion of a topic, note that it happened and then do your own research and analysis.

In science, each new set of data and consequent analysis should be added to the existing array for a given topic. Progressing towards a greater understanding is an incremental affair, especially given than a large proportion of studies and data are flawed in some way:

The scientific community doesn't produce an output of nice, neat tablets of truth, pronouncements come down from the mountain, however. It produces theories that are then backed by varying weights of evidence: a theory with a lot of support stands until deposed by new results. But it's not that neat in practice either. The array of theories presently in the making is a vastly complex and shifting edifice of debate, contradictory research results, and opinion. You might compare the output of the scientific community in this sense with the output of a financial market: a staggeringly varied torrent of data that is confusing and overwhelming to the layperson, but which - when considered in aggregate - more clearly shows the way to someone who has learned to read the ticker tape.

So what should we take away from the results of the two ongoing primate studies of life span and health under calorie restriction? After two decades one shows a modest boost to life span, the other no increase, and both show health benefits resulting from calorie restriction - though to different degrees. The control groups are fed differently, one allowed to eat as much as they like, the other on a set diet that has more calories than the restricted group. The composition of the diets in the two studies are also different. Even the genetic heritage of the rhesus monkeys involved is different enough for scientists to consider it significant, given the many but tenuous relationships to longevity found in the human genome over the past decade.

When looking beyond these studies to the broader context of data derived from a range of human studies and countless studies in mice, we see that calorie restriction absolutely, definitely has a large positive impact on health and longevity in shorter-lived mammals, and a large positive impact on measures of health in humans.

The first important point to consider is that these studies add to the weight of data and theory suggesting the effect of calorie restriction on the life span of longer-lived primates is small. Consider that any study is going produce results somewhere statistical map of what is possible and plausible: if two studies both show no extension or only a modest extension of life, then there would have to be a good reason to continue to believe that a large extension of life is possible. This concurs with the present scientific consensus and reasonable expectations: if calorie restriction could produce a 40% extension of maximum human life span, as it does in mice, then we'd have known about it since the age of antiquity. Our history is rife with cloistered groups that practiced austere lifestyles, after all, and many of them existed in periods of comparative wealth wherein suitable levels of nutrition were readily available.

A second important point is that this latest primate data in no way detracts from the health benefits produced by calorie restriction and demonstrated in numerous human studies. These research results are impressive: if calorie restriction were a drug, people would be falling over themselves to get a hold of it, as it leads to benefits that go far beyond anything that medical science can presently offer a basically healthy individual.

The future of calorie restriction research at the level of investigation and understanding - as opposed to attempts to build calorie restriction mimetic drugs - will, I suspect, involve a great deal of thought on how to reconcile significant beneficial effects on measures of health and disease risk with an apparently small beneficial effect on life span. That isn't an intuitive outcome given the view of aging as an accumulation of damage, and the straightforward relationship between better health measures and greater life span extension in shorter-lived mammals like mice or rats. What is does indicate is that some of the differences in metabolism between mammals species are very significant when it comes to life span: one hypothesis is that some of the beneficial metabolic changes brought about in mice by calorie restriction are essentially already running by default in your average human, and account for our present longevity in comparison to similarly sized mammals.

So from the perspective of a dispassionate observer of metabolic science, calorie restriction continues to offer a tremendous and ever-deepening opportunity to really dig into the operation and evolution of mammalian biochemistry. From the perspective of those of us who want to live very much longer than our predecessors, calorie restriction has to be nothing more than a common sense health practice, akin to flossing and exercise, but not something that we hang unrealistic hopes on. Real progress in living longer must come from medical science, from efforts to build rejuvenation biotechnologies that can repair the damage that causes aging. Absent advances in longevity medicine we will age and die just like our ancestors, no matter what we eat; taking care of our health is, like supporting research initiatives in longevity science, one more optimization to help us live long enough to see the deployment of therapies to treat and reverse aging.

Comments

This study doesn't show that CR wouldn't increase lifespan in primates or humans. The mortality results are from older monkeys. From rodent studies we know that CR initiated later doesn't extend lifespan as much. So it's not surprising that older monkeys aren't living longer. To provide evidence that rodent studies aren't transferable to humans or primates, further mortality studies on the younger monkey cohort are needed. The study seems to show what we already know: CR provides less longevity benefits the later it is initiated.

Posted by: Christopher at September 4th, 2012 2:09 PM

Regards humans in history. Humans present a very large population far larger than that of any study in CR. The greater number of centenarians in some populations has been attributed to moderate CR.

It is also likely that some humans may exhibit mutations conferring the benefits of CR, we would have to look at the gene expression of centenarians and supercentenarians to see if it is similar or not to that caused by CR. If the gene expression profiles are similar, even if only in some, it would be probable evidence for CR working in humans.

Also from what I've heard CR can work in some species of rodents all the way down to 50% and is rumored could work down at even lower levels if not for death by starvation. IF this is true a CR-mimetic could in theory break the 50% limit when it comes to changes in gene expression and might allow for even longer lifespan..

As for these two studies it would be interesting to see what the weights of the primates were compared to wild animals. It may be that in both cases the CR was too moderate, and both the CR and control fell within normal or slightly less than normal consumption levels for these animals.

Posted by: darian smith at January 28th, 2014 7:52 PM

Also I should add regards the primate studies it would be interesting to note protein intake, and whether there was protein supplementation in the feed as it appears some primates require reduced protein intake for some of the effects of CR(IGF-1 levels).

IT has to be seen what the normal levels of protein are for the animal in the wild, even if the calorie reduction also reduced protein, it may still have resulted in higher than normal protein intake for this type of animal.

It would also have to be seen the type of protein fed, some types are said to raise IGF-1 which may mean that even the reduced IGF-1 might not have matched or gone below wild type.

Posted by: darian smith at January 28th, 2014 8:21 PM

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