E. Bömsch/Imagebroker/FLPA
Rhesus monkeys on calorie-restricted diets age just as quickly as their chubbier counterparts.
To those who enjoy the pleasures of the dining table, the news may come as a relief: drastically cutting back on calories does not seem to lengthen lifespan in primates.
The verdict, from a 25-year study in rhesus monkeys fed 30% less than control animals, represents another setback for the notion that a simple, diet-triggered switch can slow ageing. Instead, the findings, published this week in Nature1, suggest that genetics and dietary composition matter more for longevity than a simple calorie count.
“To think that a simple decrease in calories caused such a widespread change, that was remarkable,” says Don Ingram, a gerontologist at Louisiana State University in Baton Rouge, who designed the study almost three decades ago while at the National Institute on Aging (NIA) in Bethesda, Maryland.
When the NIA-funded monkey study began, however, studies of caloric restriction in short-lived animals were hinting at a connection. Experiments had showed that starvation made roundworms live longer. Other studies had showed that rats fed fewer calories than their slow and balding brethren maintained their shiny coats and a youthful vigour. And more recently, molecular studies had suggested that caloric restriction — or compounds that mimicked it — might trigger a cascade of changes in gene expression that had the net effect of slowing ageing.
In 2009, another study2, which began in 1989 at the Wisconsin National Primate Research Center (WNPRC) in Madison, concluded that caloric restriction did extend life in rhesus monkeys. The investigators found that 13% of the dieting group died from age-related causes, compared with 37% of the control group.
One reason for that difference could be that the WNPRC monkeys were fed an unhealthy diet, which made the calorie-restricted monkeys seem healthier by comparison simply because they ate less of it. The WNPRC monkeys’ diets contained 28.5% sucrose, compared with 3.9% sucrose at the NIA. Meanwhile, the NIA meals included fish oil and antioxidants, whereas the WNPRC meals did not. Rick Weindruch, a gerontologist at the WNPRC who led the study, admits: “Overall, our diet was probably not as healthy.”
Further, the WNPRC control group probably ate more overall, because their meals were unlimited, whereas NIA monkeys were fed fixed amounts. As adults, control monkeys in the WNPRC study weighed more than their NIA counterparts. Overall, the WNPRC results might have reflected an unhealthy control group rather than a long-lived treatment group. “When we began these studies, the dogma was that a calorie is a calorie,” Ingram says. “I think it’s clear that the types of calories the monkeys ate made a profound difference.”
“When we began these studies, the dogma was that a calorie is a calorie.”
Researchers studying caloric restriction in mice have become accustomed to mixed results, which they attribute to genetic diversity among strains. Genetics probably explains part of the variation between the monkey studies, too, as the NIA monkeys were descended from lines from India and China, whereas the Wisconsin monkeys were all from India.
The molecular effects of caloric restriction have also turned out to be complicated. Using compounds such as resveratrol, found in red wine, scientists have triggered the stress response that caloric restriction activates, which shuts down non-vital processes in favour of those that ward off disease. But hopes that ageing could be delayed by targeting a single gene or protein in a single molecular pathway have faded, as researchers have learned that the key pathways vary according to the animal.“It may take us a decade to sort out longevity networks,” says David Sinclair, a geneticist at Harvard Medical School in Boston, Massachusetts.
Meanwhile, there is a dearth of evidence that caloric restriction slows ageing in humans. Observational studies have found that people of average weight tend to live longest3. Nir Barzilai, a gerontologist at Albert Einstein College of Medicine in New York, says that the centenarians he studies have led him to believe that genetics is more important than diet and lifestyle. “They’re a chubby bunch,” he says.
A more nuanced picture would suit Ingram, who enjoys an occasional feast of Louisiana crawfish. Ingram says that he looks forward to studies of how diet composition, rather than caloric intake, affects ageing. “Is the human lifespan fixed?” he asks. “I still don’t believe that for a minute.”
- Journal name:
- Nature
- Volume:
- 488,
- Pages:
- 569
- Date published:
- ()
- DOI:
- doi:10.1038/488569a
- See also News & Views
Overall, our diets may not be healthy. - I agree with this, because it's now a lot of diseases that exist today
Regards,
VooHealth - fruits for diet
As a primatologist, I note that Amy Maxmen's report on the longevity and diet (Nature, 488, 569: 2012) fails to acknowledge the most obvious genetic difference in the longevity studies conducted in rodents and monkeys. While it is the norm to use mostly inbred rodent strains in experiments, for such studies in monkeys, the used individuals are not inbred. In humans, inbreeding to the level of rodent strains used in such experiments is not tolerated!
"When we began these studies, the dogma was that a calorie is a calorie".
Caloric restriction should be viewed as an important condition for longevity, but not a sufficient one. In a recent study that summarized our work in preventing, halting, and reversing chronic disease <sup>1</sup>, we showed that what one eats in the context of a healthy lifestyle is critical, in addition to how much one eats. Thus, the quality of the diet the monkeys were fed may have over-ridden the quantity.
<sup>1</sup>. Pre-print full text version can be accessed at (http://stip.gatech.edu/wp-content/uploads/2012/02/LRD-UPDATE_TFSC_7_REV.pdf).
This study could reveal the true meaning of the paradigm of caloric restriction. The biggest lesson that this paradigm brings to us is that the intake of excess of energy causes disease and shortens life, but the adequacy of caloric intake prevents diseases and makes life achieve the fullness of its genetic planning.
I am currently writing a review article on fitness, nutrition, and the metabolic basis of chronic disease. However, I am also an example of someone who was very overweight at one point that now does competitive Masters Swimming and have kept a record of what I have done over the last 12 years. (No I don’t work out 24 hours a day and eat grass clippings). A calorie is a calorie but the balanced nutritional intake in an animal determines the metabolic homeostasis necessary for a functional and effective physiological profile. Arthur Kornberg in the book, “The Golden Helix” noted the paucity of nutritionists in the biochemical world at one point. Calories are a metric that is useful and easily interpreted by the general public. Is it the “perfect” criteria-No. But for public health purposes, it is adequate when it is presented in conjunction with the other useful information we typically see on food labels.
These animal studies are very difficult to interpret and frankly, I think Nature is doing a disservice publishing studies that may be confusing and possibly not reliable. The epigenetic people and the nutritionists need to sit down and have a beer (a light one) together. There’s the future of this field. I can envision Dr. Kornberg smiling.
The conclusion of the study "genetics is more important than diet and lifestyle." is not a new thing but the finding "drastically cutting back on calories does not seem to lengthen lifespan." is the real issue. But personally I feel there are many hopes, particularly when it says "ageing could be delayed by targeting a single gene or protein in a single molecular pathway", Moreover the key pathways vary according to the animal. Of course human metabolism is much different from the monkeys. Moreover the word "mixed results" is a very good political language in modern scientific discoveries. It looks the study does not give any specific direction to the common people. It will add more confusion to the subject.
The conclusion of the study "genetics is more important than diet and lifestyle." is not a new thing but the finding "drastically cutting back on calories does not seem to lengthen lifespan." is the real issue. But personally I feel there are many hopes, particularly when it says "ageing could be delayed by targeting a single gene or protein in a single molecular pathway", Moreover the key pathways vary according to the animal. Of course human metabolism is much different from the monkeys. Moreover the word "mixed results" is a very good political language in modern scientific discoveries. It looks the study does not give any specific direction to the common people. It will add more confusion to the subject.
"Calorie restriction falters in the long run
Genetics and healthy diets matter more for longevity."
I think we need to rework this title.
"Conflicting reports on the health benefits of CR for Rhesus primates"
We have conflicting reports here and many papers that support calorie restriction. We have a small sample size. I am curious as to how the authors measured "oxidative stress" (lower in CR Rhesus). We have lower incidents of cancer in CR Rhesus and for late start monkeys significantly lower glucose, triglyceride, and cholesterol. Obviously CR has been shown to have health benefits – even in this study that does not show increased longevity – let's make this title reflect that.
It is too bad that this simplistic approach to longevity did not work. However, twiddling one dial seldom works in complex biological systems. The pursuit of human enhancement, including enhanced lifetimes, will no doubt go on and no doubt there will be some successes.Perhaps we need to start thinking more about the societal consequences of such efforts before we go too far down that path.
http://scienceforthefuture.blogspot.com/