Abstract
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.
Highlights
Calorie restriction (CR), commonly defined as a 2040% reduction in calorie intake, is one of the most effective interventions for the modulation of aging
Apart from lifespan, calorie restriction delays the development of some aging-related diseases including diabetes, cancer, atherosclerosis, neurodegenerative and respiratory failures, increasing the healthspan [19, 20], so we investigated the effect of sole calorie or quantity intake restriction on the healthspan
Our results suggest that the enhanced fatty acid biosynthesis and metabolism and inhibited carbon metabolism are key determinants of the lifespan extension after different dietary interventions
Summary
Calorie restriction (CR), commonly defined as a 2040% reduction in calorie intake, is one of the most effective interventions for the modulation of aging. It was reported that time-limited feeding can prevent metabolic disorders in mice fed a high-fat diet without reducing calorie intake [18]. To test whether a reduction in the quantity of food alone or calorie restriction alone can extend a lifespan, we subjected mice to five diet and energy regimens (n=30 per group) wherein the NF group was the normal control group, the LF group solely restricted calorie intake, the HDR group solely restricted quantity intake and the NDR group is the traditionally reported calorie restriction intervention with both calorie and quantity intake restriction. Apart from lifespan, calorie restriction delays the development of some aging-related diseases including diabetes, cancer, atherosclerosis, neurodegenerative and respiratory failures, increasing the healthspan [19, 20], so we investigated the effect of sole calorie or quantity intake restriction on the healthspan
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