Living a healthier and longer life is as simple as cutting down on calories. Numerous studies on various animals have shown that a restricted-calorie diet can lead to a healthier and longer lifespan. While this elixir to longevity may sound simple, most people find that eating less is less easily achieved than they imagined.

In the latest research on longevity and calorie intake, scientists at the Howard Hughes Medical Institute in the United States found that in mice a reduced-calorie diet led to a 10 percent longer life. However, an even more dramatic find from the study was that by combining reduced calorie intake with a time-restricted diet — with the mice being fed only at night, which is their most active time of day — the animals lived 35 percent longer.

The new study suggests that the body’s daily rhythm plays a significant role in this longevity effect. The reduced-calorie diet plus a nighttime eating schedule led to the mice tacking on an extra nine months to their typical two-year median lifespan, stated the researchers following over four years of research on hundreds of mice. Recent years have seen the rise of many popular diet plans that focus on what’s known as intermittent fasting, such as fasting on alternate days or eating only during a period of six to eight hours per day. To unravel the effects of calories, fasting, and daily, or circadian, rhythms on longevity, the researchers undertook an extensive fouryear experiment. The team housed hundreds of mice with automated feeders to control when and how much each mouse ate for its entire lifespan.

Some of the mice could eat as much as they wanted, while others had their calories restricted by 30 to 40 percent. And those on calorie-restricted diets ate on different schedules. Mice fed the low-calorie diet at night, over either a two-hour or 12- hour period, lived the longest, the team discovered. The results suggest that timerestricted eating has positive effects on the body, even if it does not promote weight loss.

In a related study conducted earlier at the US Department of Agriculture’s Human Nutrition Research Center on Aging (HNRCA), scientists had found that calorie restriction extends the lifespan of animals ranging from worms and flies to mice, rats, and primates. Those experiments reported weight loss, improved glucose regulation, lower blood pressure, and reduced inflammation through a low-calorie diet.

For people, a diet plan equivalent to that in mice would limit eating to daytime hours. But, replicating the same systematic study protocols employed in other animals is difficult in humans, as people cannot be expected to live in a laboratory environment or eat measured food portions for extended periods needed to conclude the experiments.

Scientists are just beginning to understand how calorie restriction slows aging at the cellular and genetic level. The first controlled study of calorie restriction in humans, called the Comprehensive Assessment of Longterm Effects of Reducing Intake of Energy, or CALERIE, conducted by researchers at HNRCA, found that even a modest reduction in calories was remarkably beneficial for reducing signs of aging.

As an animal ages, genes linked to inflammation tend to become more active, while genes that help regulate metabolism become less active. The study on mice showed that a low calorie-diet timed to the most active period offset these genetic changes as mice aged.

These studies also demonstrate that even if you are restricting your calories but not eating at the right times, when you tend to be most active, you would not be getting the full benefits of caloric restriction. Further studies on how calorie restriction affects the body’s internal clocks as we age are needed to help scientists find new ways to extend the healthy lifespan of humans. That could come through calorie-restricted diets, or through drugs that mimic those diets’ effects.

Finding a drug that can boost your circadian clock, would allow scientists to conduct tests in the laboratory and examine whether it extends lifespan, said the research team at HHMI in the conclusion to their report.

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