How does dieting extend your life?

Cutting back on calories can make you leaner and live longer, an effect often attributed to the weight loss and metabolic changes that come with dieting. On October 9, a laboratory study published in Nature challenges the conventional wisdom about how dieting can extend life. This is one of the largest studies of its kind to date.

The study, which involved nearly a thousand mice that were either fed a low-calorie diet or periodically fasted, found that the treatment did cause weight loss and related metabolic changes, but other factors, including immune health, genetics and physiological markers of resilience, appeared to better explain the link between reduced calorie intake and longer lifespan.

"Changes in metabolism are important, but they don't extend lifespan," said Gary Churchill, a geneticist at the Jackson Laboratory in the United States and one of the study leaders. The results of this study reveal the complexity and individuality of the body's response to calorie restriction.

Scientists have previously found that calorie restriction, a method of long-term restriction of food intake, can extend the lifespan of laboratory animals, and some studies have shown that intermittent fasting, which involves short periods of food deprivation, can also extend lifespan.

To further understand how this dietary approach works, the researchers monitored the health and lifespan of 960 mice. Each mouse had different genes and came from a different population to reflect human genetic diversity. Some mice were put on a calorie-restricted diet, another group followed an intermittent fasting regimen, and others were allowed to eat freely.

The results showed that reducing calorie intake by 40% had the best effect in extending lifespan, but intermittent fasting and less severe calorie restriction also extended average lifespan. The dieting mice also showed favorable metabolic changes, such as reduced body fat and blood sugar levels.

However, the effects of dieting on metabolism and lifespan did not always move in tandem. To the researchers’ surprise, the mice that lost the most weight through the calorie-restricted diet tended to die earlier than mice that lost relatively little weight.

This suggests that there are processes other than simple metabolic regulation that drive the body's response to caloric restriction. The most important factors in extending lifespan are traits related to immune health and red blood cell function. Another key factor is the animal's overall resilience to the stress of reduced food intake, which may be encoded by the animal's genes.

“The intervention was a stress,” Churchill said. “The animals that recovered best lost the least weight, maintained immune function, and lived longer.”

The findings could reshape how scientists think about studying dieting in humans. In a clinical trial of a low-calorie diet in healthy, non-obese people, researchers found that the intervention helped reduce metabolic rate, a short-term effect that is thought to have long-term benefits for lifespan.

However, Churchill's team's mouse data suggest that metabolic measures may reflect healthy lifespan, that is, the life span without chronic disease and disability, but other indicators are needed to show that this "anti-aging" strategy can actually extend lifespan.

"This study deepens our understanding that health and lifespan are not the same thing," says Daniel Belsky, an epidemiologist at Columbia University's Mailman School of Public Health, but cautions against extrapolating too much from mice to humans.