More than a decade ago, researchers at the Pennington Biomedical Research Center in Baton Rouge began recruiting young, healthy Louisianans to voluntarily go hungry for two years. In addition to cutting their daily calories by 25 percent, the dozens who enrolled also agreed to a weekly battery of tests; blood draws, bone scans, swallowing a pill that measures internal body temperature.
All that sticking and scanning and starving was in the name of the Comprehensive Assessment of Long-Term Effects of Reducing Intake of Energy, or Calerie—the largest human clinical trial ever to look at the effects of calorie restriction on aging. The National Institutes of Health-funded study also included sites at Washington University in St. Louis and Tufts in Boston. But only the Pennington participants had to also spend 24 sedentary hours inside a sealed room that recorded the contents of their every breath.
These are the measures that scientists (and some study participants) are willing to go to understand how a spartan diet impacts the aging process. Calorie restriction is one of the least ridiculous strategies in the burgeoning field of longevity science. Studies going back to the mid-1930s have shown over and over that cutting calories by 25-50 percent lets yeast, worms, mice, rats, and monkeys live longer, healthier lives, free from age-related disease. But there’s far less consensus on the mechanisms through which it works.
Which is probably why attempts to mimic fasting with medicines have so far all failed FDA approval. Calerie was designed to ask that question in humans and the first randomized control trial to do so. The researchers chose a 25 percent restriction (between 500 and 800 calories) because it seemed humanly feasible and still likely to show an effect, based on previous animal studies. With 10,000 Americans turning 65 every day, the stakes for good science supporting healthy human aging have never been higher. Unfortunately, the latest results don’t exactly clear things up.
In a paper published in Cell Metabolism, researchers from Pennington reported for the first time on their whole room calorimeter experiments—the sealed metabolic chambers they stuck participants in for 24 hours. Pennington is one of the few places in the world with these hotel-room-sized micro-environments, the most rigorous way to measure how many calories a person burns and where they come from—fat, protein, or carbohydrates.
After a night of fasting, participants entered the calorimeter promptly at 8:00am, and until 8:00am the following day they weren’t allowed to leave or exercise. Researchers delivered meals through a small, air-locked cupboard. As fresh air circulated into the room, the air flowing out went through a series of analyzers to measure the ratio of carbon dioxide to oxygen. Nitrogen measurements from urine samples help calculate a total picture of each participant’s resting metabolism.
The picture that emerged was that cutting calories, even modestly, lowered people’s metabolism by 10 percent. Some of that could be attributed to weight loss (on average folks lost 20 pounds over two years). But according to the study’s authors, the majority of the change had more to do with altered biological processes, which they observed through other biomarkers like insulin and thyroid hormones. “Restricting calories can slow your basal metabolic rate—the energy you need to sustain all normal daily functions,” says endocrinologist and lead author Leanne Redman. When the body uses less oxygen to generate all its required energy, it produces fewer byproducts of metabolism, things like free radicals that can damage DNA and other cellular machinery. “After two years, the lower rate of metabolism and level of calorie restriction was linked to a reduction in oxidative damage to cells and tissues.”
