Reducing calories and eating at the right time of day prolongs the lives of mice

Summary: Limiting calories and eating only during the most active part of the day helped extend the lifespan of the mice.

Source: HHMI

A recipe for longevity is simple, if not easy to follow: eat less. Studies on various animals have shown that calorie restriction can lead to a longer and healthier life.

Now, new research suggests that the body’s daily rhythms play a big role in this longevity effect. Eating only during their most active time of day significantly extended the lifespan of mice on a calorie-restricted diet, Howard Hughes Medical Institute researcher Joseph Takahashi and colleagues report May 5, 2022, in the journal Science.

In his team’s study of hundreds of mice over four years, a low-calorie diet alone extended the animals’ lives by 10%. But feeding the mice only at night, when the mice are most active, extended life by 35%. This combo — a low-calorie diet plus a nighttime meal schedule — added an extra nine months to the animals’ typical two-year median lifespan. For people, a similar plan would limit meals to daytime hours.

The research helps unravel the controversy around diets that emphasize eating only at certain times of the day, says Takahashi, a molecular biologist at the University of Texas Southwestern Medical Center.

Such plans may not accelerate weight loss in humans, as a recent study in the New England Journal of Medicine reported, but they could lead to health benefits that add up to a longer lifespan.

The findings of Takahashi’s team highlight the crucial role of metabolism in aging, says Sai Krupa Das, nutrition scientist at the Jean Mayer USDA Center for Human Nutrition Research on Aging, who was not involved in the work. . “This is a very promising and landmark study,” she says.

fountain of Youth

Decades of research have shown that calorie restriction extends the lifespan of animals ranging from worms and flies to mice, rats and primates. These experiments report weight loss, better glucose regulation, lower blood pressure and reduced inflammation.

But it’s been difficult to systematically study calorie restriction in people, who can’t live in a lab and eat measured food portions their entire lives, Das says. She was part of the research team that conducted the first controlled study of calorie restriction in humans, called the Comprehensive Evaluation of the Long-Term Effects of Reduced Energy Intake, or CALERIE. In this study, even a modest reduction in calories “was remarkably beneficial” in reducing the signs of aging, Das says.

Scientists are just beginning to understand how calorie restriction slows aging at the cellular and genetic level. As an animal ages, genes related to inflammation tend to become more active, while genes that help regulate metabolism become less active. Takahashi’s new study found that calorie restriction, especially when timed for the mice’s nocturnal activity period, helped offset these genetic changes as the mice aged.

A matter of time

The past few years have seen the rise of many popular diets that focus on what is known as intermittent fasting, such as fasting every other day or eating only for six to eight hours per week. day. To unravel the effects of calories, fasting, and daily or circadian rhythms on longevity, Takahashi’s team undertook an extensive four-year experiment. The team housed hundreds of mice with automated feeders to monitor when and how much each mouse ate over its lifetime.

Some of the mice could eat as much as they wanted, while others had their calories restricted by 30-40%. And those on low-calorie diets ate on different schedules. Mice fed the low-calorie diet at night, over a two-hour or 12-hour period, lived the longest, the team found.

The results suggest that a time-limited diet has positive effects on the body, even if it does not promote weight loss, because the New England Journal of Medicine suggested study. Takahashi points out that his study also found no difference in body weight in mice following different eating schedules – “however, we found profound differences in lifespan,” he says.

This cartoon shows mice looking at a vending machine
Experiments that tested various diets in mice found that the animals lived the longest on a low-calorie diet with daily fasting periods. 1 credit

Rafael de Cabo, a gerontology researcher at the National Institute on Aging in Baltimore, says the Science paper” is a very elegant demonstration that even if you restrict your calories but are not [eating at the right times]you don’t get the full benefits of calorie restriction.

Takahashi hopes learning how calorie restriction affects the body’s internal clocks as we age will help scientists find new ways to extend healthy human lifespans. This could be from low-calorie diets or from medications that mimic the effects of such diets.

See also

This shows the outline of two heads

In the meantime, Takahashi takes a lesson from his mice – he limits his own feeding to a 12-hour period. But, he says, “if we find a drug that can boost your clock, then we can test it in the lab and see if it extends lifespan.”

About this longevity research news

Author: Press office
Source: HHMI
Contact: Press office – HHMI
Picture: Image is credited to Fernando Augusto

Original research: Access closed.
Circadian alignment of early calorie restriction promotes longevity in male C57BL/6J mice” by Victoria Acosta-Rodríguez et al. Science


Abstract

Circadian alignment of early calorie restriction promotes longevity in male C57BL/6J mice

Caloric restriction (CR) prolongs lifespan, but the mechanisms by which it does so remain poorly understood. Under RC, mice self-impose chronic cycles of 2-hour feeding and 22-hour fasting, raising the question of whether calories, fasting, or time of day are causal. We show that 30%-CR is sufficient to prolong life by 10%; however, daily interval fasting and circadian alignment of diet acted together to extend lifespan by 35% in male C57BL/6J mice.

These effects are independent of body weight. Aging induces a generalized increase in the expression of genes associated with inflammation and a decrease in the expression of genes encoding components of liver metabolic pathways from ad-lib fed mice. Nocturnal CR improves these age-related changes.

Thus, circadian interventions promote longevity and provide a perspective to further explore the mechanisms of aging.

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