[Frontiers in Bioscience 2, e108-115, November 1, 1997]

	[Frontiers in Bioscience 2, e108-115, November 1, 1997] Reprints PubMed CAVEAT LECTOR
	EFFECT OF AGING AND CALORIC RESTRICTION ON INTESTINAL SUGAR AND AMINO ACID TRANSPORT Ronaldo P. Ferraris Dept of Pharmacology and Physiology, UMDNJ-New Jersey Medical School, 185 South Orange Ave., Newark, NJ 07103 Received 7/17/97 Accepted 10/2/97 7. EFFECT OF CALORIC RESTRICTION ON INTESTINAL NUTRIENT TRANSPORT Caloric restriction is the balanced reduction of the protein, carbohydrate and fat content of the diet without reduction of its micronutrient (vitamins and minerals) content. In practice, an animal on a calorie-restricted diet consumes an amount of food at 60 - 70% that of an animal fed to satiety (ad libitum). Over 60 years of research in rodents and other small animals have shown that caloric restriction can dramatically extend lifespan, maintain vitality, and reduce the incidence of age-associated disease (63). How do absorptive systems in the small intestine adapt to lifelong caloric restriction and therefore a chronic reduction in amounts of luminal nutrients that need to be absorbed? A striking development in age-related changes in intestinal nutrient transport has been the recent finding that intestinal nutrient transport (normalized to weight, length or entire intestine) differs markedly between chronically calorie-restricted and ad libitum fed mice (64). This effect of caloric restriction on intestinal nutrient transport is best elucidated by estimating the total intestinal absorptive capacity (SUMJ). This is done by integrating the in vitro uptake per cm along the length of the small intestine, then expressing SUMJ as a function of metabolic body weight (BW^0.75) to correct for calorie restriction -induced differences in metabolic mass (since metabolic rate increases with body weight as BW^0.75 among mammals). Casirola et al found SUMJ for sugars and amino acids to be about 50% higher in 24 months old calorie-restricted mice compared to same age controls (ad libitum fed). The ratio SUMJ /BW^0.75 was 80% greater in calorie-restricted mice, suggesting that their intestine has the potential to absorb nutrients at almost two-fold the rate in mice fed ad libitum. The proximate mechanism underlying this dramatic increase in SUMJ is not intestinal mass which is similar between calorie restricted and those fed ad libitum, but an equally dramatic increase in transport per mg of intestine (figure 2). Switching 24 months old mice fed ad libitum to CR for one month does not significantly change BW, SUMJ, and intestinal mass. Caloric restriction had no effect on intestinal permeability (49, 64). Figure 2. Transmembrane transport of glucose, fructose and proline was each greater () in the small intestine of calorie-restricted (CR) than in that of ad libitum* (AL) fed, same age (24 months old) mice. Casirola et al (65) switched 32 months old calorie-restricted mice to one month of ad libitum feeding, and found BW to increase by 35%, and SUMJ to decrease by 30% compared to those in same age controls that remained calorie-restricted. Interestingly, they found no changes in mRNA levels of sugar transporters associated with changes in SUMJ. SUMJ/BW^0.75 was over 50% greater in mice that remained calorie-restricted compared to same age mice switched to ad libitum feeding. Intestinal weights again remained similar, but uptake per mg of intestine decreased by 42% with the switch to ad libitum feeding. Calorie restricted mice switched to ad libitum feeding for only three days (the lifetime of most intestinal cells) had significant increases in body weight but no changes in SUMJ. Cao and Ferraris (unpublished observations) tracked changes in SUMJ of fructose in young adult mice sacrificed 1, 2, 10, 24, and 270 days after CR. They found modest increases in SUM/J 24 days after caloric restriction. However, 270 d after caloric restriction, SUMJ and SUMJ /BW^0.75 were 60 and 120%, respectively, greater in calorie-restricted mice as compared to same age controls fed ad libitum. As in the previous study, they found no changes in mRNA levels of fructose transporters associated with changes in SUMJ. Caloric restriction seems to be associated with marked increases in intestinal absorptive capacity. This adaptive increase is developed over a long period of time and can be reversed by ad libitum feeding of a much shorter duration. However, changes in levels of transporter mRNA and in intestinal mass are not detected. Since the change in SUMJ/BW^0.75 is so dramatic, it indicates that calorie-restricted mice can absorb a much greater amount of nutrients per unit metabolic mass than ad libitum mice, and probably implies that an increase in intestinal nutrient absorption rates is a critical adaptation to caloric restriction.

[Frontiers in Bioscience 2, e108-115, November 1, 1997]
Reprints
PubMed
CAVEAT LECTOR

EFFECT OF AGING AND CALORIC RESTRICTION ON INTESTINAL SUGAR AND AMINO ACID TRANSPORT

Ronaldo P. Ferraris

Dept of Pharmacology and Physiology, UMDNJ-New Jersey Medical School, 185 South Orange Ave., Newark, NJ 07103

Received 7/17/97 Accepted 10/2/97

7. EFFECT OF CALORIC RESTRICTION ON INTESTINAL NUTRIENT TRANSPORT

Caloric restriction is the balanced reduction of the protein, carbohydrate and fat content of the diet without reduction of its micronutrient (vitamins and minerals) content. In practice, an animal on a calorie-restricted diet consumes an amount of food at 60 - 70% that of an animal fed to satiety (ad libitum). Over 60 years of research in rodents and other small animals have shown that caloric restriction can dramatically extend lifespan, maintain vitality, and reduce the incidence of age-associated disease (63). How do absorptive systems in the small intestine adapt to lifelong caloric restriction and therefore a chronic reduction in amounts of luminal nutrients that need to be absorbed? A striking development in age-related changes in intestinal nutrient transport has been the recent finding that intestinal nutrient transport (normalized to weight, length or entire intestine) differs markedly between chronically calorie-restricted and ad libitum fed mice (64).

This effect of caloric restriction on intestinal nutrient transport is best elucidated by estimating the total intestinal absorptive capacity (SUMJ). This is done by integrating the in vitro uptake per cm along the length of the small intestine, then expressing SUMJ as a function of metabolic body weight (BW^0.75) to correct for calorie restriction -induced differences in metabolic mass (since metabolic rate increases with body weight as BW^0.75 among mammals). Casirola et al found SUMJ for sugars and amino acids to be about 50% higher in 24 months old calorie-restricted mice compared to same age controls (ad libitum fed). The ratio SUMJ /BW^0.75 was 80% greater in calorie-restricted mice, suggesting that their intestine has the potential to absorb nutrients at almost two-fold the rate in mice fed ad libitum. The proximate mechanism underlying this dramatic increase in SUMJ is not intestinal mass which is similar between calorie restricted and those fed ad libitum, but an equally dramatic increase in transport per mg of intestine (figure 2). Switching 24 months old mice fed ad libitum to CR for one month does not significantly change BW, SUMJ, and intestinal mass. Caloric restriction had no effect on intestinal permeability (49, 64).

Figure 2. Transmembrane transport of glucose, fructose and proline was each greater (*) in the small intestine of calorie-restricted (CR) than in that of ad libitum (AL) fed, same age (24 months old) mice.

Casirola et al (65) switched 32 months old calorie-restricted mice to one month of ad libitum feeding, and found BW to increase by 35%, and SUMJ to decrease by 30% compared to those in same age controls that remained calorie-restricted. Interestingly, they found no changes in mRNA levels of sugar transporters associated with changes in SUMJ. SUMJ/BW^0.75 was over 50% greater in mice that remained calorie-restricted compared to same age mice switched to ad libitum feeding. Intestinal weights again remained similar, but uptake per mg of intestine decreased by 42% with the switch to ad libitum feeding. Calorie restricted mice switched to ad libitum feeding for only three days (the lifetime of most intestinal cells) had significant increases in body weight but no changes in SUMJ.

Cao and Ferraris (unpublished observations) tracked changes in SUMJ of fructose in young adult mice sacrificed 1, 2, 10, 24, and 270 days after CR. They found modest increases in SUM/J 24 days after caloric restriction. However, 270 d after caloric restriction, SUMJ and SUMJ /BW^0.75 were 60 and 120%, respectively, greater in calorie-restricted mice as compared to same age controls fed ad libitum. As in the previous study, they found no changes in mRNA levels of fructose transporters associated with changes in SUMJ.

Caloric restriction seems to be associated with marked increases in intestinal absorptive capacity. This adaptive increase is developed over a long period of time and can be reversed by ad libitum feeding of a much shorter duration. However, changes in levels of transporter mRNA and in intestinal mass are not detected. Since the change in SUMJ/BW^0.75 is so dramatic, it indicates that calorie-restricted mice can absorb a much greater amount of nutrients per unit metabolic mass than ad libitum mice, and probably implies that an increase in intestinal nutrient absorption rates is a critical adaptation to caloric restriction.