Living Longer Through Diet and Calorie Restriction

Today, we look at how to make sense of the disparate results from the four primate studies on caloric restriction and lifespan.

Calorie restriction in primates to extend lifespan. Will it work? There’s only one way to find out. There have been four investigations of calorie restriction and lifespan in nonhuman primates. The first was published in 2003, an analysis of the mortality of 117 rhesus monkeys followed for about 25 years in a lab, eight of whom had their Purina monkey chow restricted. The average survival of the restricted monkeys was to 32 years of age, compared to 25 years for the control monkeys. However, it was more of an observational study, since the monkeys weren’t randomly assigned. And, although in the abstract, they talk about the survival advantage and how the ad libitum monkeys—the eat-all-you-want monkeys—had more than twice the risk of death, they acknowledge deeper in the paper that the difference in death did not reach statistical significance––meaning it may have very well been a fluke. That was all we had, though, until results started trickling in from the famous pair of studies that involved randomizing about 200 rhesus monkeys to caloric restriction or more normal diets––one out of the University of Wisconsin—Madison (UW), and another from the National Institute of Aging (NIA).

The UW study reported a 30 percent caloric restriction significantly delayed disease and improved survival, but the NIA study did not. In the UW study, caloric restriction reduced the incidence of age-related diseases including cancer, cardiovascular disease, brain atrophy, muscle wasting, preserving muscle mass––demonstrating caloric restriction can delay aging. But in the NIA study, the difference in age-related diseases did not achieve statistical significance. In the UW study, the restricted monkeys lived to an average of about 29 years compared to the control monkeys, who lived closer to the average for monkeys in captivity of about 26 years old. In contrast, though one of the restricted monkeys in the NIA study became the longevity record holder for the species at age 43, on average, the restricted group didn’t live any longer than the control animals. Why the disparate results between the two studies?

In the NIA study that found no significant lifespan difference, the control group was not fed ad libitum, but rather had food portioned out to prevent excess weight gain. In contrast, in the UW study, the control monkeys could eat as much as they wanted throughout the day, so ended up weighing more than the NIA control animals. Of course, caloric restriction would improve the health and survival of overweight monkeys, just as weight loss would be beneficial for overweight people. But the null results in the NIA study suggest that normal-weight people might not benefit from restricting further.

The NIA monkeys were also fed a healthier diet. The diet in the UW study, where they saw significant benefit to cutting down, was an ultra-processed concoction of largely milk protein, corn oil, corn starch, and table sugar, whereas the NIA diet actually included unprocessed plant foods such corn, soybeans, and wheat, and so actually had some phytonutrients. About 29 percent of the UW diet was straight sugar, compared to 4 percent in the NIA diet. (American adults get about 17 teaspoons of sugar a day, which is about 13 percent of calories.) The contrasting findings suggest that the worse your diet is, the more important it is to eat less of it.

The fourth study was on grey mouse lemurs, among the smallest of primates, standing just three inches tall. Those randomized to a 30 percent caloric restriction compared to the ad libitum control group lived a whopping 50 percent longer. And not just average lifespan, but maximal lifespan. The maximum lifespan was boosted by about 20 percent. However, the “calorie restricted” group still weighed heavier than their wild counterparts; so again, this may just be an illustration of the harms of obesity and another indictment against all-you-can-eat buffets. Also, those in the calorie restriction group experienced an acceleration of age-related loss of grey matter throughout their brains, though this did not appear to translate into cognitive or behavioral differences.

Pooling the three rhesus monkey studies together, there seemed to be lower age-related mortality, but no significant difference in average lifespans overall between the caloric restriction groups and the control groups. Given the time and expense, there is little chance we are going to see any more long-term primate studies on caloric restriction for life extension. So, what can we draw from the primate data to date? If you’re overweight or living off junk food, eating less is a good idea.

In our next story, we discover how a slower metabolism may actually be a good thing.

Though a bane for dieters, a slower metabolism may actually be a good thing. We’ve known for more than a century that calorie restriction can increase the lifespan of animals, and the metabolic slowdown may be the mechanism. That could be why the tortoise lives 10 times longer than the hare. Rabbits can live 10 to 20 years, whereas “Harriet,” a tortoise evidently collected from the Galapagos by none other than Charles Darwin himself in the 1830s, lived until 2006. Slow and steady may win the race.

One of the ways your body lowers your resting metabolic rate is by creating cleaner-burning, more efficient mitochondria, the power plants that fuel our cells. It’s like your body passes its own fuel-efficiency standards. These new mitochondria create the same energy with less oxygen, and produce less free radical “exhaust.” After all, your body is afraid famine is afoot, and so, it is trying to conserve as much energy as it can.

The largest caloric restriction trial to date indeed found both metabolic slowing and a reduction in free radical-induced oxidative stress—both of which may slow the rate of aging. The flame that burns twice as bright burns half as long. But whether this will result in greater human longevity is an unanswered question. Caloric restriction is often said to extend the lifespan of “every species studied.” But that isn’t even true of all strains within a single species. Some scientists don’t think calorie restriction will improve human longevity at all; others suggest a 20 percent calorie restriction starting at age 25 and sustained for 52 years could add 5 years onto your life. Either way, the reduced oxidative stress would be expected to improve our healthspan.

Members of the Calorie Restriction Society, self-styled CRONies (for Calorie-Restricted Optimal Nutrition), appear to be in excellent health, but they’re a rather unique, self-selected bunch of individuals. You don’t really know until you put it to the test. Enter the CALERIE study, the Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy, the first clinical trial to test the effects of caloric restriction.

Hundreds of non-obese men and women were randomized to two years of 25 percent calorie restriction. They only ended up achieving half that but lost about 18 pounds and three inches off their waists, wiping out more than half of their visceral abdominal fat. That translated into significant improvements in cholesterol levels, triglycerides, insulin sensitivity, and blood pressures. Eighty percent of those who were overweight when they started were normal weight by the end, compared to a 27-percent increase in those who became overweight in the control group.

In the famous Minnesota Starvation Study that used conscientious objectors as guinea pigs during World War II, the study subjects suffered both physically and psychologically, experiencing depression, irritability, and loss of libido. The subjects started out lean, though, and had their calorie intake cut in half. The CALERIE study ended up being four times less restrictive, only about 12 percent below baseline calorie intake, and enrolled normal-weight individuals, which in the U.S. these days means overweight, on average. As such, the CALERIE subjects experienced nothing but positive quality-of-life benefits, with significant improvements in mood, general health, sex drive, and sleep. They only ended up eating about 300 fewer calories than they were eating at baseline. So, they got all these benefits—the physiological benefits, the psychological benefits—all from only cutting about a snack-sized bag of chips worth of calories from their daily diets.

What happened at the end of the trial, though? In the Minnesota Starvation Study and calorie deprivation experiments done on Army Rangers, as soon as subjects were released from restriction, they tended to rapidly regain the weight, and sometimes even more. The leaner they started out, the more their bodies seemed to drive them to overeat to pack back on the extra body fat. In contrast, after the completion of the CALERIE study, even though their metabolism was slowed, they retained about 50 percent of the weight loss two years later. They must have acquired new eating attitudes and behaviors that allowed them to keep their weight down. After extended calorie restriction, for example, cravings for sugary, fatty, and junky foods may actually go down.