The Interaction of Calorie Restriction and Circadian Rhythm

Researchers here note that feeding and fasting time appears to meaningfully change the effects of long-term calorie restriction on life span in short-lived mammals. Much of the more recent literature on intermittent fasting, fasting mimicking strategies, and calorie restriction appears, to me at least, to lean towards the conclusion that time spent in a state of hunger is an important factor in the degree to which the intervention slows aging. It is interesting to compare this with protein restriction studies in which hunger and calorie intake is not meaningfully different between restricted animals and the control group. One might think that there are two very different sets of mechanisms at play, (a) those involving cell reactions to a diminished amount of specific proteins versus (b) cellular reactions to the regulatory signaling generated in the state of hunger, such as increased ghrelin secretion.

The modification of diet for longevity has long been of interest, research generally having been conducted in animal experiments. Caloric restriction (CR) is known to contribute to a prolongation of lifespan, even in higher animals. Recently, caloric restriction, fasting, and fasting intervals, and the time of eating with consideration to species-appropriate circadian alignment has been investigated. While caloric restriction itself has been found in numerous species to result in a significant prolongation of lifespan, it has also been shown that fasting regimens can independently promote longevity as well as improve deteriorated metabolic functions.

Researchers have reported that circadian alignment in addition to fasting promotes longevity independently of caloric restriction in male mice. The study compares the contribution of adjusted feeding times in addition to fasting in five caloric restriction groups on behavioral, metabolic, and molecular outcomes using automated feeders. Diet energy was restricted by 30% in all caloric restriction groups of mice fed under five caloric restriction protocols: two of the groups were fed during the active (night) or non-active (day) period for 2 hours; two groups were fed regularly every 90 minutes during half (12 hours) of the active or non-active period; and one group was fed every 160 minutes throughout the 24 hour day.

The results are intriguing. Caloric restriction itself extended the lifespan by 10%; when the fasting time was added, the lifespan was increased to 20%; and when the feeding time was aligned to the active period, the lifespan was further extended to 35%, demonstrating that when food intake is restricted to an appropriate time of the day there is an additional benefit to caloric restriction and fasting on lifespan.

Link: https://doi.org/10.1111/jdi.14033