The Benefits of Calorie Restriction are Based on Calorie Intake, not Food Quantity

Researchers here note that reduction in the calorie content in the diet is the important trigger for the benefits of calorie restriction, not reductions in the quantity of food ingested. The practice of calorie restriction, reducing calorie intake while still obtaining optimal micronutrient intake, has been shown to extend life span in near all species and lineages tested to date. Firm data on human life span has yet to be obtained, and is expected to be modest, on the order of a few years only, but short-term beneficial changes to the operation of metabolism are quite similar between mice and humans. Research into calorie restriction has given rise to a broad field of development of calorie restriction mimetic drugs, targeting many of the same cellular stress response mechanisms that are triggered by a low calorie intake. One shouldn’t expect miracles from this line of work: we know the limits of calorie restriction in humans, and while it is certainly beneficial, it doesn’t greatly change the duration of a human life.

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Although calorie restriction has been reported to extend lifespan in several organisms, animals subjected to calorie restriction consume not only fewer calories but also smaller quantities of food. Whether it is the overall restriction of calories or the coincidental reduction in the quantity of food consumed that mediates the anti-aging effects is unclear. Here, we subjected mice to five dietary interventions. We showed that both calorie and quantity restriction could improve early survival, but no maximum lifespan extension was observed in the mice fed isocaloric diet in which food quantity was reduced.

Mice fed isoquant diet with fewer calories showed maximum lifespan extension and improved health among all the groups, suggesting that calorie intake rather than food quantity consumed is the key factor for the anti-aging effect of calorie restriction. Midlife liver gene expression correlations with lifespan revealed that calorie restriction raised fatty acid biosynthesis and metabolism and biosynthesis of amino acids but inhibited carbon metabolism, indicating different effects on fatty acid metabolism and carbohydrate metabolism. Our data illustrate the effects of calories and food quantity on the lifespan extension by calorie restriction and their potential mechanisms, which will provide guidance on the application of calorie restriction to humans.