Experiment in mice helps dissect effects of calorie restriction, fasting and time of feeding on lifespan extension

In mice, caloric restriction – known to prolong lifespan – had the most beneficial impact when the animals consumed their limited calories on a schedule so that they fasted for at least 12 hours, and when they ate at nighttime, nocturnal rodents’ normal feeding time. The results provide evidence that circadian interventions such as timed feeding enhance the well-known lifespan benefits of caloric restriction. Caloric restriction (CR) – which typically involves cycles of time-restricted feeding and long fasting – prolongs lifespan, though the mechanisms by which it does so remain unclear. Although decreased energy intake is commonly thought to be the critical factor, it is possible that the timing of food intake, and also the frequency of feeding, are key components in extending lifespan. To better understand the influences of these various factors, Victoria Acosta-Rodriguez et al. designed experiments to control both caloric intake of mice and the timing of their eating. Mice housed alone with access to a running wheel were fed defined amounts of food at specific times of day. This was done across five different calorie-restricted groups of mice that differed only in the daily pattern – not amount – of food consumed, as well as in a control group in which eating was unrestricted. The authors compared behavioral, metabolic, and molecular outcomes in the mice throughout their lifespans. Caloric restriction extended lifespan as expected, but it worked best when feeding was restricted so that the animals fasted for at least 12 hours. Importantly, the degree of lifespan extension was longer in CR mice when food was consumed during the nighttime. The authors further showed that calorie restriction at night ameliorated age-related changes, including increases in gene expression associated with inflammation. Thus, say the authors, maximal benefits of CR can be achieved by a fasting interval of >12 hours in which the time-restricted feeding occurs in an organism’s natural active phase.