Aging weakens the body's circadian rhythms, and this weakening is linked to disease and shorter life. Calorie restriction slows aging, but people find it hard to stick with. Time-restricted eating without reducing calories has become a popular alternative. Yet almost all studies have been done in obese mice or on unhealthy diets, and few have compared males and females. This work fills that gap: it tests the long-term effects of time-restricted eating in healthy mice on a normal diet. Nearby in our archive are papers on quantum memory, primate lifespan, and daily schedules, but this one stands apart: it directly links circadian rhythms, nutrition, and mammalian aging.
The researchers took 264 female and 264 male C57BL/6J mice at two months of age and housed each one individually in a cage with a running wheel and an automated feeder. For the first eight weeks, all ate freely. Then, at four months, some mice were switched to a 12-hour nighttime feeding window (from ZT12 to ZT24), another group to an 8-hour window (from ZT14 to ZT22), and the rest continued to eat freely. Food was provided in excess of what the mice consumed, so there was no calorie restriction. Health was assessed every six months: body composition was measured by nuclear magnetic resonance, frailty was checked across 31 parameters, blood tests were taken, and glucose tests were run. After death, each mouse was necropsied and examined for disease. This long experiment with hundreds of animals allowed, for the first time, a precise comparison of how different feeding windows affect lifespan and health in both sexes.
Time-restricted eating benefited both sexes. Mice on the 12-hour window gained less weight and fat, and in males the 8-hour window amplified this effect. Both regimens slowed the rise of frailty: in females, the 8-hour window reduced the frailty index from 12 to 24 months; in males, it reduced it from 12 to 18 months on the 12-hour window and to 24 months on the 8-hour window. Importantly, the 8-hour window made the mice eat 9–23% less without forced calorie restriction, meaning spontaneous calorie restriction occurred. The main result: the 8-hour window extended lifespan only in males. Median lifespan rose from 818 to 916 days, that is, by 12%, and maximum lifespan by 3%. Females showed no lifespan extension, even though their health improved. In addition, in males the 8-hour window delayed the onset of age-related diseases by 52 days, while females showed no such effect.
The work shows that time-restricted eating is beneficial even on a normal diet, without obesity or unhealthy eating. This sets it apart from most neighboring studies, where the effect was tested in models with metabolic disorders. Here, for the first time, it is proven that an 8-hour nighttime window extends lifespan in male mice, while in females it improves health without changing lifespan. The findings highlight the importance of aligning meals with the body's internal clocks and point to sex differences in response to such interventions. This is a step toward understanding how simple lifestyle changes can slow aging in humans.
Further studies could test whether time-restricted eating works if started in old age rather than in youth. It is important to find out whether the regimen can be stopped in old age without losing the benefits. It is also worth studying how shifting the feeding window relative to the sleep and activity phase matters, and comparing effects across different mouse strains. A separate question is why females do not live longer despite better health: perhaps they need stronger calorie restriction or longer fasting. Finally, the impact on the cardiovascular system, which was not measured in this work, needs to be assessed.
The results could influence dietary recommendations for people, especially for preventing age-related diseases. They are also important for gerontology and chronobiology, since they link circadian rhythms to lifespan.
The immediate steps include testing the regimen in old mice and studying the molecular mechanisms behind the sex differences, for example through gene expression analysis in the liver.
The work addresses a fundamental problem in gerontology: why calorie restriction extends life but is hard to endure, and how to find easier interventions. It also raises the question of sex differences in aging, which remains understudied. Unresolved is the contradiction between improved health and no lifespan extension in females, which points to a complex relationship between health and longevity.
Contrary to popular belief, in this experiment male mice outlived females: median lifespan was 818 days for males versus 694 for females. In mammals, females usually live longer, but in C57BL/6J mice the results are inconsistent. Perhaps the females were cold in individual cages without nesting material and spent more energy on heating.
Not published on arXiv. Here are its page, the PDF and the formalization: you can check it yourself, not only read our account.