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

6. REGULATION OF SUGAR AND AMINO ACID TRANSPORT BY DIET

Aging reduces the ability of physiological systems to adapt to changes in the environment (53). The small intestine of young adults can easily adapt to acute and chronic changes in diet by altering the number of brushborder (54) and basolateral (55) sugar transporters. The adaptation occurs 1 - 2 days after the change in diet.

The adaptive capability of the small intestine in the aged has been challenged in several studies, though only a couple of these are on sugar and amino acid transporters. Young adults adapt to dietary calcium concentrations by increasing intestinal transport when dietary levels are low, and by decreasing transport when its levels are high. The larger the change in dietary levels, the greater the change in transport rate. Armbrecht et al (56) demonstrated that the amplitude of this intestinal adaptation progressively decreased with age, so that in rats 12 months of age, rates of calcium uptake and levels of calcium binding protein no longer changed with dietary calcium levels. Similarly, rates of intestinal sugar uptake and site density of sugar transporters are directly proportional to dietary carbohydrate concentrations (54, 56, 57). Rates of intestinal transport of nonessential amino acids are also directly proportional to levels of dietary protein (56, 57). The transport rates of essential or potentially toxic amino acids, however, may be inversely proportional to dietary protein levels (see Ferraris and Diamond (58) for a detailed discussion). In young adults, the time course of this adaptive change is rapid and occurs within 1 - 2 days (59). For Na⁺-dependent glucose transport, the time course of diet-induced changes in uptake is mainly due to cell migration times, because only crypt cells perceive the dietary signal for glucose transporter regulation (48). In order for intestinal glucose transport activity to change, these crypt cells have to first migrate to replace mature enterocytes lining the villus. This is due to the fact that mature cells cannot be reprogrammed to change their SGLT-1 mediated transport activity (48). In contrast, intestinal fructose transport adapts much more rapidly to changes in dietary fructose level, probably because mature cells can also change their GLUT5-mediated transport activity.

The time course of adaptive change in Na⁺-dependent glucose transport basically remains unchanged in aged mice (45), because cell migration rates in most intestinal regions are also independent of age. The time course of adaptive changes in fructose, proline, aspartate and alanine uptakes was also independent of age, suggesting that aged mice adapt just as readily as young mice to changes in dietary levels of nutrients.

In mice, age seems to affect the amplitude of the change in sugar and nonessential amino acid transport in response to a change in the dietary carbohydrate and protein levels, respectively (60). Young adult mice enhance their sugar transport by about two-fold in the proximal intestine. In contrast, aged mice enhance their transport by only 1.5 fold despite the fact that their baseline transport rate was already lower than that of young mice. In contrast to the distal region of small intestine of young mice, that of aged mice also failed to respond to a change in dietary nutrient levels. Although the age-related differences in the amplitude change were modest, they were consistent from one transporter to another, and are similar to age-impaired adaptations in levels of hepatic glycolytic enzymes, of intestinal calcium transporters, and of pancreatic enzymes to changes in levels of dietary nutrients (56, 61, 62).