By now, there are quite a few studies that show restricting calories can improve health and enhance longevity. But new research suggests this longevity effect can be turbocharged even further by playing to the body’s daily rhythm and only eating when the metabolism is most active.

Researchers at the Howard Hughes Medical Institute fed hundreds of male mice a reduced-calorie diet — 30% fewer calories than those consumed by control mice that were allowed to eat as much as they wanted — for over four years. This intervention improved their lifespan by 10%, a significant but nevertheless expected outcome seeing how decades of research have found calorie restriction extends lifespan in all kinds of animals ranging from worms and flies to rats and primates.

But when calorie restriction was combined with a daily fasting interval, the lifespan of the mice ballooned by a staggering 35%. That’s an extra nine months on top of a mouse’s typical two-year median lifespan. For a human, that would be equivalent to an extra twenty years of life.

The mice on a restricted calorie diet ate on different schedules. Mice fed the low-calorie diet at night, when rodents are the most active, over either a two-hour or 12-hour feeding window, lived the longest.

However, while the time-restricted diet improved longevity a lot, it did not promote weight loss. This may finally explain why many diet plants that emphasize eating only at certain times of the day don’t actually seem to speed up weight loss in humans. But if these findings are any indication, the health benefits could significantly increase our lifespans if we commit. Humans are most active during the day, so there should be no calorie intake after the evening, according to the researchers led by Joseph Takahashi, a molecular biologist at the University of Texas Southwestern Medical Center.

“This is a very elegant demonstration that even if you are restricting your calories but you are not [eating at the right times], you do not get the full benefits of caloric restriction,” says Rafael de Cabo, a gerontology researcher at the National Institute on Aging in Baltimore, who was not involved in the study.

A 2021 study on 6,400 people, from eight days old up to age 95, in 29 countries, found that 1-year-olds burn calories 50% faster than adults. However, energy expenditure changed very little from early adulthood through age 60 in both males and females, contrary to popular belief. After age 60 though, our metabolism seems to go downhill, with older people experiencing a 25% slower metabolism than at mid-life. It’s no coincidence that age-related diseases start to increase in frequency just as our metabolism begins to decline.

If the new study is any indication, some of the ill effects of a less active metabolism may be offset through calorie restriction and a balanced timing of meals. This notion seems to be supported by other research, such as this 2021 study on mice published in Nature Metabolism, which found eating a single meal daily led to lower blood sugar, better use of fat stores for energy, less frailty as the rodents aged, and longer lifespans.

Takahashi and colleagues are also looking into how drugs, and possibly supplements, that mimic these dietary effects could also enhance longevity in humans. The researcher himself is taking the lessons he learned from his lab mice to heat, having restricted his own eating schedule to a 12-hour window.

“If we find a drug that can boost your clock, we can then test that in the laboratory and see if that extends lifespan,” Takahashi said.

The new findings were reported in the journal Science.