ADAPTATIONS OF INTESTINAL NUTRIENT TRANSPORT TO CHRONIC CALORIC RESTRICTION IN MICE

Lifelong caloric restriction increases median and maximum Life span an d retards the aging process in many organ systems of rodents. Because the small intestine absorbs a reduced amount of nutrients each day, do es lifelong caloric restriction induce adaptations in intestinal nutri ent transport? We initially compared intestinal transport of sugars an d amino acids between 24-mo-old mice allowed free access to food [ad l ibitum (AL)] and those provided a calorically restricted [40% less tha n ad libitum (CR)] diet since 3 mo of age. We found that CR mice had s ignificantly greater transport rates for D-glucose, D-fructose, and se veral amino acids and had significantly lower villus heights. Total in testinal absorptive capacities for D-glucose, D-fructose, and L-prolin e were each 40-50% greater in CR mice; absorptive capacity normalized to metabolic mass (body weight(0.75)) was similar to 80% greater in CR mice. Comparison of uptakes in aged AL and CR mice with previously pu blished results in young AL mice suggests that caloric restriction del ays age-related decreases in nutrient transport. In contrast to publis hed studies in hibernation and starvation, chronic caloric restriction enhances not only uptake per milligram but also uptake per centimeter . We then switched 24-mo-old AL mice to a calorie-restricted diet for 1 mo and found that short-term caloric restriction has no effect on in testinal nutrient transport, intestinal mass, and total absorptive cap acity. Thus chronic but not short-term caloric restriction increases i ntestinal nutrient transport rates in aged mice, and the main. mechani sm underlying these increases is enhanced transport rates par unit int estinal tissue weight.