In a new study published in Science, researchers show that: Calorie-restricted and time-limited feeding has an additive effect on mouse lifespan ..
Calorie restriction is considered the first intervention to ensure that aging is an adaptive phenomenon. The first study was conducted in rats in the 1930s and showed that a significant 20% to 30% calorie restriction significantly extended lifespan compared to a free-fed (free) control group. .. ..
The reality is more complex, as these early results were promising. First, calorie restriction can return calorie counts to normal levels, as laboratory animals tend to overeat when food is plentiful. Therefore, it may not work well for those who are already counting calories. There has been virtually no human attempt at dramatic calorie restriction, as it is difficult to maintain.
Second, in most rodent experiments, animals were fed once daily. They desperately consumed a limited amount of food in about two hours, and then went fast for 22 consecutive hours. Today, this will be called an intermittent fast. This is another intervention that is gaining popularity due to its seemingly health-promoting properties. .. There are several intermittent fasting regimens, including “daily”, but some of the most popular include eating only during the 2-12 hour time frame.
Therefore, it is difficult to determine whether calorie restriction works well in mice and rats with low calories or low feeding times. This new study seeks to provide an answer using something scientists in the 1930s didn’t have: an automated feeder.
If you are a mouse, eat at night
The researchers divided the male mice into six groups. The control group was easily fed day and night and fed freely. All other groups were calorie-restricted – received 30% less calories than the mice in the AL group consumed. The first calorie-restricted group received food all day long, and an automatic feeder distributed one food pellet every 160 minutes to eliminate the effects of intermittent fasting. The second calorie restriction group was fed only 2 hours during the day, the third was fed 12 hours during the day, the fourth was fed 2 hours at night, and the fifth was fed 12 hours at night.
In the free-fed group, the median lifespan was 792 days. This is quite common in this particular very popular strain (Black 6). This is important because in some studies the controls are short-lived and can question the results.
All calorie restriction groups showed a significant increase in lifespan compared to controls, but there were significant differences. The first group, all-day-fed mice, lived about 10% longer than the controls. The two groups fed during the day approached each other. The second group lived 21% longer and the third group lived 19% longer on average than the controls. The last two groups were clear winners, with the median lifespan of the fourth group increasing by 35% and the fifth group increasing by 33.4%.
Obviously, mice fed at regular intervals throughout the day may have interrupted sleep and reduced lifespan extension. Researchers acknowledge that this requires further investigation. Mice are nocturnal animals, so if forced to eat during the day, this is unnatural for them and may explain the difference between night and day groups.
There are two important points from the data. Calorie restriction and intermittent fasting have an additive effect, and shortening the feeding window to 2 hours seems to be of little value compared to the 12-hour window.
Researchers have confirmed that calorie restriction has a clear metabolic effect. Insulin levels increased with age in the control group, but this increase was diminished in all restricted groups. Insulin levels in calorie-restricted young mice were similar to those in control young mice, but the former showed lower blood glucose levels and improved insulin sensitivity.
The researchers also analyzed gene expression in the liver. The transcriptomes of young and old mice in the control group were clustered separately due to obvious age-related changes. The transcriptomes of young mice in the calorie restriction group were clustered separately. This means that calorie restriction affects gene expression in young mice.
Finally, all old calorie-restricted mice are clustered in the transcriptome between older and younger calorie-restricted mice in the control group, indicating that interventions attenuate changes in the transcriptome with age. .. About 50% of the age-related changes in gene expression were reversed by all calorie restriction regimens.
Researchers have discovered 159 genes that respond specifically to intermittent fasting rather than calorie restriction, and confirm that their effects are at least somewhat additive. The 69 genes were particularly protected from age-related changes in expression in the group restricted to low-calorie night feeding.
The purpose of this study is to unravel the effects of calorie restriction and intermittent fasting and to gain a better understanding of how these two interventions work. Since it is almost impossible for humans to actually significantly reduce calories, the signs that time-based feeding may be partly involved in the life-prolonging effects of calorie restriction are promising. Lack of sexual diversity is a serious limitation, as many life-prolonging interventions appear to work differently in men and women. Hopefully this will be addressed in further research.
 Acosta-Rodríguez, V. , Rijo-Ferreira, F., Izumo, M., Xu, P., Wight-Carter, M., Green, CB, & Takahashi, JS (2022) The circadian rhythm of early-onset calorie restriction is male C57BL / 6J. Extends the life of the mouse. ChemistryE.
 McKay, CM, Crowell, MF, Maynard, LA (1935). Effect of delayed growth on longevity and final body size: one figure. Nutrition Journal, Ten(1), 63-79.
 de Cabo, R. , & Mattson, MP (2019) Effects of intermittent fasting on health, aging and illness. New England Journal of Medicine, 381(26), 2541-2551.