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CR and the Primate Studies: "Eat less, live longer"

Michael R

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A hat tip to David Stern, CR Society Board Member, treasurer, and co-organizer of our amazing Calorie Restriction Society Conferences:
The University of Wisconsin at Madison is home one of the two main studies on the effects of CR in nonhuman primates. A paper centering on the University (I'm not clear on whether it's actually an University paper or is one of the many third-party sites providing campus coverage) did a story on CR focused on the primate studies. It covers a lot of the difficulties the Wisconsin study encountered, and the surprising and controversial contrast between its results and the NIA study (see here and here).  It's surprisingly well-rounded and nuanced, and certainly neither a cheerleading nor a naysaying article:

Eat less, live longer
May 19, 2015 12:00 am  •  Johanna Lee

... To this day, we continue our quest to escape aging and death. However, the secret to extending our lifetime may not lie in some magical pool of water, but by eating fewer calories. Scientists call it “caloric restriction” or “CR,” the practice of reducing calorie intake without malnutrition. Since 1935, CR has been shown to increase longevity in many animals, including worms, spiders, flies, fish, mice and rats. It is, in fact, the only dietary intervention, which consistently extends lifespan in a broad range of species. In some cases, the increase can reach up to 50 percent!
But what about in humans? Have we finally discovered the modern “Fountain of Youth?" At the Wisconsin National Primate Research Center, a study led by Ricki Colman, senior scientist, is dedicated to answering this question. For the past 26 years, the researchers have been feeding a 30 percent calorie-reduced diet to one of our close relatives ...
Initiated in 1989, the study was one of the first of its kind—an animal study spanning over two decades. The challenges were also unprecedented. “One of the main difficulties was the change in technology. We still analyze our data with old programs in order to keep consistent,” says Colman. She pointed to an ancient desktop at the corner of her office saying “That’s why we still need to keep that.” [!] Besides computer technology, experimental protocols and laboratory equipment also improved significantly. ... Halfway through the study, one of the lab freezers broke down and destroyed many valuable specimens.
Fortunately, obstacles were overcome and freezers were fixed. Colman published the results in Nature Communications in April 2014. It immediately made headlines. [The main headlines, and the consequent controversy, were more the result of a preliminary publication in Science in 2009 — MR]. The monkeys on a CR diet were thinner, had less decline of muscle mass and looked noticeably younger. Incidences of both tumors and cardiovascular diseases decreased by 50 percent, and diabetes was largely prevented. Brain function also improved, with less deterioration in regions which control motor, executive function and stress-related emotion regulation. The CR monkeys were not only healthier than controls, but they also showed lower levels of stress and anxiety in certain behavioral tests.
But did they actually live longer? The answer is yes! [in the final 2014 analysis], The average lifespan of monkeys on a regular diet is approximately 26 years, but the CR monkeys lived on average 3 years longer, a whopping 10 percent increase. The statistics suggest at any point in time, the control monkeys had 2.9 times the rate of death from age-related causes compared to those on a CR diet.
The study, however, was not short of controversy. Another study at the National Institute on Aging, beginning in 1987, used rhesus monkeys of a different genetic origin, also feeding them a 30 percent calorie-reduced diet. In this 25-year study, CR largely prevented cancer and diabetes, but cardiovascular diseases remained unchanged. More puzzling, CR did not increase lifespan, contradicting the WNPRC results.
Colman believes this is mainly due to the difference in diet between the two studies (although genetic variability could also play a role).  .... [T]he NIA diet was healthier than the WNPRC diet.  In addition, the control monkeys in the WNPRC study had unlimited access to food (imagine an all-you-can-eat buffet—every day), while the NIA control diet was restricted. It is no surprise the WNPRC control monkeys were a bit overweight and the NIA control monkeys were exceedingly thin.
The conflicting results of the two studies may simply suggest even a modest degree of dietary restriction, as in the NIA control monkeys, can improve health and survival. This explains why the lifespan of the NIA monkeys on a CR diet were not significantly longer than control. The controls were, in fact, already exceptionally long-lived—five of the 20 male controls lived past 40—which is extremely rare under the circumstances.
In the human world, the NIA monkeys would be considered health addicts, eating healthy food from natural ingredients and controlling their portions. The WNPRC monkeys, on the other hand, may more accurately reflect the high-sugar diet and over-eating of most modern Americans. With this in mind, the two studies are more complementary than contradicting.
[MR: But this still doesn't answer the question. Does either study really represent what can be anticipated from the effects of CR proper in humans? The Wisconsin primates represent tragically typical modern lifestyles. But are the Wisconsin "CR" or NIA "Control" groups proper "Controls"? Are the NIA "CR" animals really healthy-eating controls for a never-completed study of CR's true effects in rhesus monkeys, or are they actually the best that can be expected from CR in their species? And what about the genetics, and the key question of the prior husbandry of the NIA animals, which is not addressed in this story? ].
There are no plans to repeat these studies, due to the unusually long duration and high cost of conducting aging studies in monkeys. Instead, Colman is using existing samples and data to figure out how calorie restriction increases longevity.  ...
This effect, however, is not just due to losing weight by eating less. While reducing body fat may increase lifespan by preventing certain diseases, it does not actually “slow down” aging as is what happens with CR. ...
However, the idea of “starving” monkeys for the sake of research does not play well with animal rights activists. “Everybody working on monkeys becomes a target,” said Colman. She regularly receives hate mail from activists who view her work as animal cruelty and torture. Some of her colleagues have even received razor blades in the mail and other suspicious packages. The Wisconsin Primate Center building, where her office and some of the monkeys are located, is locked 24 hours a day for security. ...
Despite all the threats and pressure, Colman is undeterred. ... Her genuine care for the animals shows deeply when she talks about watching the animals get sick and, eventually, die. ... From the original 76 animals, only 14 are still alive. The study continues with the remaining animals.

So, are you ready to try a CR diet? Not so fast. Colman says “this study was not meant to be a prescription for humans, it’s only to understand the aging process.” Researchers believe the effect of CR on humans may not be as compelling as seen in animal studies. [but has the right study been done in primates? And even if you accept that it has, the question is which animal study?? -MR]. Say you were a healthy 25-year-old male. To extend your lifetime by 5 years on a CR diet, you presumably would have to decrease your calorie intake by 20 percent, for the rest of your life! If this were even possible, would it be worth it? [ smiley-rolleyes008.gif -MR]

CR is not just about eating half a burger or throwing away the last bite of cheesecake. It is about eating foods not just low in calories, but also nutrient-rich, like fruits and vegetables. Simply reducing portion size without supplementing other necessary nutrients will not work. The key is to reduce calories while staying satisfied and well nourished. [MR: Thank you ...]

In fact, a growing number of human volunteers are already trying out this type of low-calorie high-nutrient diet, called the Calorie Restriction with Optimal Nutrition diet. There is even a CR Society, established way back in 1994, with members identifying themselves as “CRONies." Studies on long-term CRONies suggest CR can indeed prevent certain aspects of human aging, including atherosclerosis and decline in heart function. Not to mention most CRONies are notably thin, which could further prevent diseases related to obesity.

But it is not all good news. Experiencing an initial period of agonizing hunger is the norm. [At least she says "initial"!  -MR]. Other side effects include feeling chilled (due to slower metabolism), decreased stamina and lowered libido. [i [i]wish-wish-wish [/i]they would say, "side effects experienced by some hard-core practitioners include ..." -MR]. The CR Society website says “any significant dietary change should be done in consultation with a knowledgeable physician.” If done improperly, serious conditions, like malnutrition, anemia, bone-loss or anorexia could occur. A 25 percent calorie reduction would be ideal, but a 50 percent reduction could starve you to death.

Although CR seems to have a positive effect on human health, we still do not know whether it actually increases lifespan in humans. Performing a long-term human study in a controlled laboratory setting does not seem like a viable (or ethical) option. Colman’s study in monkeys might be the closest we can get.

With more research, drugs mimicking the effect of CR, without the pain of starvation, may arrive in the future. We will not all live to be 120, but the possibility of living a healthy, happy and extended old age is not at all a myth. This is something Herodotus and Juan Ponce de León could never have imagined.

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