August 29, 2012 | 9
Aging researcher Thomas Kirkwood asked a roomful of scientists recently whether they thought that restricting calorie intake by 10 to 40 percent would extend lifespan, as it sometimes does in mice and roundworms. A majority of those present raised hands in assent. It has become a sort of conventional wisdom among scientists and the general public that calorie restriction extends lifespan. Even before hard scientific evidence was in, some people adopted the practice, foregoing rich desserts for the rest of their lives in the hope of arriving at a tenth or eleventh decade.
Kirkwood might get a very different response from the scientists he questioned if he asks the same question this afternoon or this evening. And it should be interesting to log onto the life-extension blogs and listservs in the wee hours.
A National Institute on Aging study published online today in Nature shows that more than 20 years of limiting calorie intake by 30 percent in a group of rhesus monkeys did not allow them to live longer than a control group of monkeys who were eating a normal, unrestricted diet. “I think the message is that a caloric restriction response, if it exists for monkeys and by implication humans, may occur only under the narrowest conditions,” says Steven N. Austad, a professor at University of Texas Health Science Center San Antonio, who wrote an accompanying commentary in Nature.
A similar monkey study of limiting dietary intake at the University of Wisconsin showed some benefit for extending lifespan, but Austad, in his Nature essay, raised the question of whether that might be related to their feeding regimen—the unrestricted Wisconsin monkeys were heavier and perhaps unhealthier and shorter-lived than the National Institute of Aging control group because they were able to eat as much as they wanted.
Other questions arose about whether the removal from the Wisconsin study analysis of some monkeys who died from non-aging-related causes might have burnished the results. “Both studies are impressive bodies of work and I have the greatest respect for both teams,” says Kirkwood. “I do think the earlier results from the Wisconsin study revealed an eagerness to show the intervention worked—entirely understandable when so much time and resource has been invested into it. Taken together, the studies give significant reason to suppose that rodents are different from long-lived primates, but that should not come as a surprise.”
All of this is not necessarily a reason to rush out to buy McDonald’s stock. Older restricted-diet monkeys at the National Institute of Aging did have healthier measures of blood glucose and a blood lipid than did their heftier companions. But it throws a chink into what many scientists—and a burgeoning dietary supplements industry (peddling resveratrol and other supplements said to mimic restriction)—thought was fast-becoming an established tenet of endocrinology and gerontology, that severely cutting calories would up the chances of living longer. Says Austad: “If we assume that rhesus monkey size in the wild approximates a healthy body weight [wild monkeys weigh less than all of those in both studies] then the Nature study suggests that reducing the diet of an overweight monkey such that it approaches the weight of a wild monkey will improve some health metrics but not extend life.”
Austad adds: “Neither of these [studies] replicates what some people are experimenting on themselves with—which is normal weight people reducing their diets to the point of emaciation in the hopes that there will be a rodent-like boost in longevity.”
Mark Mattson, a neuroscientist at the National Institute on Aging who had practiced caloric restriction for 25 years, said he changed his diet in 2010 after he recognized that many of the caloric restriction studies in rodents had afforded the restricted animals a longevity premium because the control animals were the equivalent of “couch potatoes”— like the Wisconsin control group, they were allowed to eat ad libitum, similar to humans digging into the potato chip bag when watching the game on TV.
Mattson continues research on fasting several days a week and eating normally the rest to determine whether it may help prevent the buildup of aberrant proteins observed among those with chronic diseases like Alzheimer’s or Parkinson’s, even if lifespan remains static. Mattson himself now follows an intermittent fasting diet.
The gainsaying about the National Institute of Aging study has already started. A whole cadre of researchers devote themselves to research related to caloric restriction and are likely to continue. “I think it’s unfortunate because it’s is such a long experiment that it will probably never be replicated,” says Matt Kaeberlein of the University of Washington, on the National Institute of Aging study. “It’s really a single piece of data that can’t be interpreted and likely never will be able to be interpreted. Those of us who work in shorter-lived model organisms know very well that every once in awhile a lifespan experiment happens where CR doesn’t extend median or maximum survival. The difference is that we have repeated the experiment dozens of times.”
More primate research on caloric research continues, but some of the assumptions about a restricted diet have surely been shaken. One benefit of the new skepticism that will arise from this new study is a redirection of gerontology away from any temptation to view the field as a means to achieve Methuselah-like lifespans and a return to its main focus of optimizing health and avoidance of chronic disease up to the time of death.
The news you can use: exercise and maintain a healthy weight. Nothing profound here from the National Institute on Aging. Your mother probably beat the scientists to the punch.
Image source: National Institute on Aging