PUMPING IRONY: Eat Less, Live Longer?

I once tracked my daily caloric intake in college for a nutrition class project, and it came in around 1,200 calories — a goodly portion of which resulted from beer consumption. So, I guess I can say that I have some experience with calorie restrictions, however mindless my intent. I’ve never bothered to monitor my diet so closely in the years since, but if my modest septuagenarian paunch is any indication, I’ve come a long way from my college-era eating patterns.

Certain longevity experts, however, might lament my inability to maintain the spartan dietary regimen of my college days (minus the beer, probably). Limiting our calories, they’ve long argued, may extend our lifespans.

The basic idea is this: Humans, like other larger mammals, tend to live longer than small animals, a fact scientists attribute to our slower metabolic rates, which also produce fewer free radicals and cause less cellular damage. The less food the body is asked to process, the slower our metabolism, reducing the damage of free radicals and thus extending our lifespans.

That’s the theory, anyway. It worked with lab rats, Clive McCay proclaimed back in 1935, and other researchers have subsequently hailed the results in various rodents, worms, flies, and primates. But human studies have raised more questions than they’ve answered.

Results of the most recent effort, published last week in the journal Nature Aging, suggest that reducing caloric intake by 25 percent over a two-year period may reduce overall mortality risk by 10 to 15 percent — about the same effect as a person would expect from giving up smoking. “In worms, flies, and mice, calorie restriction can slow biological processes of aging and extend healthy lifespan,” notes senior study author Daniel Belsky, PhD, a scientist at the Robert N. Butler Columbia Aging Center. “Our study aimed to test if calorie restriction also slows biological aging in humans.”

Humans, of course, live a lot longer than lab animals, which makes such calculations a bit dicey. Belsky and his team calculated the mortality risk among the 220 study participants by measuring specific biomarkers from blood samples collected prior to the study and then again 12 and 24 months later. Their analysis of methylation marks on the DNA extracted from white blood cells showed that the calorie restriction didn’t lower an individual’s biological age, but it reduced the pace at which their body was aging during the two-year period.

How those study participants would fare under the same protocol over the long term, however, is anybody’s guess. And, as a practical matter, Belsky’s findings are not likely to spark much more interest in serious calorie cutting than already exists.

“Calorie restriction is probably not for everyone,” admits study coauthor Calen Ryan, PhD. “Our findings are important because they provide evidence from a randomized trial that slowing human aging may be possible. They also give us a sense of the kinds of effects we might look for in trials of interventions that could appeal to more people, like intermittent fasting or time-restricted eating.”

Any future research, however, will likely be dogged by the same issues critics have raised in the past: questions about control-group guidelines, previous eating patterns, and the challenges of human-based studies.

Writing in Science in the News, Princeton University biostatistician Isabella Grabski, PhD, notes that comparisons between lab animals in experimental groups and those in control groups can often be skewed by the amount of food the control group is allowed to eat. If they’re given free rein to gorge themselves while the other group is placed on a tightly restricted diet, she writes, “it is difficult to disentangle any benefits due to calorie restriction from the harmful effects of the control group’s diet.”

The benefits of calorie restriction may also be overestimated based on a lab animal’s previous eating patterns. Those accustomed to feasting prior to agreeing to the dietary restrictions would naturally show more health benefits than those who typically ate more moderately. “Hence, it is possible that the benefits from calorie restriction may only be due to how unhealthily those animals might otherwise live,” she explains. “In animals that already eat healthy portions, it could be the case that calorie restriction may not yield any particular advantage.”

Finally, conducting these sorts of studies on humans is much more challenging than working with lab animals. “We simply cannot (and should not) exert the same degree of control over human subjects as we might for rats,” Grabski notes.

Belsky based his study on data from the 2019 CALERIE trial, the results of which Grabski calls into question. She notes that many of those practicing calorie restrictions were overweight before the trial began. That makes it difficult to separate the health benefits they received from the restricted diets from the weight they managed to lose. “It is already well known that going from being overweight to a healthy weight has a positive impact on the body,” she argues. “However, the trial results do not clearly answer the question of whether metabolic changes due to calorie reduction beyond a normal diet can improve health.”

Layer on the questionable ethics of encouraging a dietary protocol that may lead to disordered eating, and you’ve created a major research muddle. If there’s any upside, she argues, it’s that these studies may eventually help us better understand the aging process. “Addressing this mystery may help lead to other antiaging efforts, even if this particular calorie restriction work never makes it out of the lab.”

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