December 1992: 374-377
Age-Related Changes in the Gastrointestinal Tract Shiro Hosoda, M.D., Ph.D., Tadao Bamba, M.D., Ph.D., Shinobu Nakago, M.D., Ph.D., Yoshihide Fujiyma, M.D., Ph.D., Shigeru Senda, M.D., Ph.D., and Makoto Hirata, M.D.
Introduction
Morphologically, the age-related changes in the gastrointestinal (GI) system are represented by parenchymal atrophy and sclerotic changes of the stroma. Probably because changes in the GI system are less marked than changes in the other organ systems, there is no consensus regarding the ageassociated changes in the height of villi and the depth of crypts.' In this paper, our discussion of the function of the GI system is divided into three sections: 1) motility, 2) digestion and absorption, and 3) immune function. Age-related changes in these three functions will be described based mainly on our studies. Gastrointestinal Motility
The basic swallowing pattern of the esophagus appears to be preserved in the aged,2 although agerelated changes in gastric emptying time are less well understood. The most important problem in the elderly is that constipation is four to eight times more common than in younger subjects. Figure 1 shows changes in the strength of the intestinal wall with aging; muscular tonus is associated with GI motility. The strength of the intestinal wall was highest in the 10- to 19-year-old age group and decreased with age. These findings indicate that an age-related decrease in the wall elasticity of the rectum and descending colon may contribute to constipation in the elderly. Digestion and Absorption
Digestion and absorption are the raison d'Ctre of the GI system. These functions do not appear to be qualitatively altered by aging, and although they are somewhat reduced, the reduction is masked by the The authors are at the Department of Internal Medicine, Shiga University of Medical Science, Japan. 374
reserves of the GI system. It is useful to explore changes in digestion and absorption by focusing on three specific areas of GI function: brush border membrane enzyme activity (which plays an important role in digestion at the cell membrane), sugar absorption, and fat absorption. Brush Border Membrane Enzyme Activity The brush border membrane (BBM) of small intestine produces terminal digestive enzymes that catalyze the degradation of disaccharides and oligopeptides. Lactase activity on BBM is known to vary, depending on age and race.3 We analyzed agerelated changes in the activities of BBM enzymes in rats. The activities of alkaline phosphatase, maltase, and leucine aminopeptidase were significantly higher in the old group than in the young group. This age-related elevation in BBM enzyme activities may be related to the finding that the turnover rate of small intestinal cells is longer in old rats than in young rats, so that the more abundant mature cells stay on the villi, elevating enzyme activity. Alternatively, the age-related reduction in the absorptive function of the gut could elevate the substrate levels within the lumen, leading to a compensatory elevation in enzyme a ~ t i v i t y . ~ Carbohydrate Absorption Carbohydrates are essential sources of energy. No consistent view has been established about the influence of aging on their absorption. D-Xylose is absorbed via the small intestine and its degradation rate in the body is low. Because of these features, the urinary D-xylose excretion ratio has been used as an index of carbohydrate absorption. This index, however, is likely to be affected by renal function. In a 25-g D-xylose absorption test,5 the five-hour urinary D-xylose excretion ratio was significantly lower in the old group (over age 50) than in the young group (under age 50). We calculated a theoretical intestinal absorption of 5 g of D-xylose by determining the ratio of urinary excretion following Nutrition Reviews, Vol. 50, No. 12
->
T
2
E
v
Descending Colon
n a
0 Young
q 1
0
Old
Transverse
colon Ascending colon
Ileum Jejunum Duodenum
jt* *
, 2
4
6 8 DGlucose (rnM)
10
0 10 20 30 40 50 60 70 (age)
\ \ \ \ I \ \ \ 9 19 29 39 49 59 69 79 Figure 1. Strength of the bowel wall with increasing age, by decade. From Iwasaki, Kyoto Prefectural University.
intravenous injection of 5 g of D-xylose in the same persons. The D-xylose absorption ratio was 65% in both the young and old groups. This finding indicates that the age-related reduction in D-xylose absorption is caused by reduced renal function, and that intestinal absorption of D-xylose is not affected by aging. Descriptions of age-related changes in D-glucose absorption vary from one report to another, a discrepancy that seems attributable to different experimental methods.6 Bearing these discrepancies in mind, Hirata et al.' studied D-glucose absorption in young and old rats using two methods-everted intestine and purified brush border membrane vesicles (BBMV)-in order to determine which stage of D-glucose absorption shows age-related changes. First, everted gut sacs were used to measure D-glucose absorption by differences in electrical potential (Figure 2). In the old group, the half-saturation concentration was significantly higher than in the young group, a finding suggesting that the affinity of D-glucose to carrier molecules is reduced by aging. However, examination of D-glucose uptake in BBMV, purified by calcium precipitation, showed no difference in affinity (Figure 3). These results indicate that the age-associated reduction in affinity does not represent a change in the properties of the carriers themselves, but rather, an impairment caused by such factors as the distribution of carriers in the intestine or changes in the unstirred water layer. Fat Absorption Because fat is insoluble in water, its digestion and absorption within the digestive tract and the epitheNutrition Reviews, Vol. 50, No. 12
r **1
Young Old
Young Old
Figure 2. Age-related differences (mean *SD) in transmural electrical potential (in mV) induced by D-glucose in the presence of sodium (n = 5). Statistical significance indicated as follows: * p < 0.05; **p < 0.01.
lial cells of small intestinal mucosa require complicated mechanisms. Digestion and absorption of long-chain fatty acids, which comprise a majority of food components, involve the following steps: 1) formation of an emulsion in the stomach, 2) hydrolysis of triglycerides in the presence of pancreatic lipase, 3) formation of a complex micelle composed of bile acids, fatty acids, and monoglycerides; 4) diffusion of individual fatty acids through the microvillous membrane; 5 ) resynthesis of triglycerides in mucosal cells; 6) formation of chylomicrons; and 7) transfer of chylomicrons to lymph ducts. Each step occurs independently and is rate limiting. Because absorption of fatty acids is so complex, the influence of aging on this process is thought to be greater than its influence on absorption of other nutrients.8 Numerous studies' have investigated the effects of aging on fat absorption, and some have indicated that fecal fat excretion following excessive fat ingestion is increased in persons over 70 years of age. When '311-triolein and '"I-RISA were simultaneously loaded with a test meal, their digestion and absorption were normal in persons aged 60-79 years but were slightly reduced in those over 80 years. An 375
Immune Function
i'
A
0 Young
-
-
1.0
Y
0.5
E
Young
Old
2
Young
Old
Figure 3. Age-related differences (mean *SD) in D-glucose uptake by rat brush border membrane vesicles in the presence of sodium ( n = 4).
age-related reduction in palmitic acid uptake was observed in an experiment in which fat digestion and absorption were analyzed via 14C-palmitic acid uptake in rat intestinal mucosa. When intestinal lipids were analyzed by subsequent silica-gel thinlayer chromatography, the early stages of esterification of palmitic acid into triglyceride were reduced in the old group. These results suggested an age-related impairment of fat resynthesis within the intestinal mucosa. When the activity of enzymes catalyzing this resynthesis was examined, an age-related reduction in acyl CoA:monoglyceride acytltransferase was observed' (Table 1). We think that the age-related reduction in pancreatic lipase and bile secretion also may be involved in agerelated impairment of fat digestion and absorption. Table 1. Effect of Aging on Activity of the Enzyme Acyl-CoA:Monoglyceride Acyl Transferase
Group
n
Young Old
5 5
Total Microsomal Specific Protein (mg) Activity
Total Activity
*
9.58 2 5.71 6.06 k 1.03 74.57 32.42 7.36 t 2.51 3.30 5 1.69 20.40 k 7.16 D NS
Age-Related Changes in the Gastrointestinal Tract Shiro Hosoda, M.D., Ph.D., Tadao Bamba, M.D., Ph.D., Shinobu Nakago, M.D., Ph.D., Yoshihide Fujiyma, M.D., Ph.D., Shigeru Senda, M.D., Ph.D., and Makoto Hirata, M.D.
Introduction
Morphologically, the age-related changes in the gastrointestinal (GI) system are represented by parenchymal atrophy and sclerotic changes of the stroma. Probably because changes in the GI system are less marked than changes in the other organ systems, there is no consensus regarding the ageassociated changes in the height of villi and the depth of crypts.' In this paper, our discussion of the function of the GI system is divided into three sections: 1) motility, 2) digestion and absorption, and 3) immune function. Age-related changes in these three functions will be described based mainly on our studies. Gastrointestinal Motility
The basic swallowing pattern of the esophagus appears to be preserved in the aged,2 although agerelated changes in gastric emptying time are less well understood. The most important problem in the elderly is that constipation is four to eight times more common than in younger subjects. Figure 1 shows changes in the strength of the intestinal wall with aging; muscular tonus is associated with GI motility. The strength of the intestinal wall was highest in the 10- to 19-year-old age group and decreased with age. These findings indicate that an age-related decrease in the wall elasticity of the rectum and descending colon may contribute to constipation in the elderly. Digestion and Absorption
Digestion and absorption are the raison d'Ctre of the GI system. These functions do not appear to be qualitatively altered by aging, and although they are somewhat reduced, the reduction is masked by the The authors are at the Department of Internal Medicine, Shiga University of Medical Science, Japan. 374
reserves of the GI system. It is useful to explore changes in digestion and absorption by focusing on three specific areas of GI function: brush border membrane enzyme activity (which plays an important role in digestion at the cell membrane), sugar absorption, and fat absorption. Brush Border Membrane Enzyme Activity The brush border membrane (BBM) of small intestine produces terminal digestive enzymes that catalyze the degradation of disaccharides and oligopeptides. Lactase activity on BBM is known to vary, depending on age and race.3 We analyzed agerelated changes in the activities of BBM enzymes in rats. The activities of alkaline phosphatase, maltase, and leucine aminopeptidase were significantly higher in the old group than in the young group. This age-related elevation in BBM enzyme activities may be related to the finding that the turnover rate of small intestinal cells is longer in old rats than in young rats, so that the more abundant mature cells stay on the villi, elevating enzyme activity. Alternatively, the age-related reduction in the absorptive function of the gut could elevate the substrate levels within the lumen, leading to a compensatory elevation in enzyme a ~ t i v i t y . ~ Carbohydrate Absorption Carbohydrates are essential sources of energy. No consistent view has been established about the influence of aging on their absorption. D-Xylose is absorbed via the small intestine and its degradation rate in the body is low. Because of these features, the urinary D-xylose excretion ratio has been used as an index of carbohydrate absorption. This index, however, is likely to be affected by renal function. In a 25-g D-xylose absorption test,5 the five-hour urinary D-xylose excretion ratio was significantly lower in the old group (over age 50) than in the young group (under age 50). We calculated a theoretical intestinal absorption of 5 g of D-xylose by determining the ratio of urinary excretion following Nutrition Reviews, Vol. 50, No. 12
->
T
2
E
v
Descending Colon
n a
0 Young
q 1
0
Old
Transverse
colon Ascending colon
Ileum Jejunum Duodenum
jt* *
, 2
4
6 8 DGlucose (rnM)
10
0 10 20 30 40 50 60 70 (age)
\ \ \ \ I \ \ \ 9 19 29 39 49 59 69 79 Figure 1. Strength of the bowel wall with increasing age, by decade. From Iwasaki, Kyoto Prefectural University.
intravenous injection of 5 g of D-xylose in the same persons. The D-xylose absorption ratio was 65% in both the young and old groups. This finding indicates that the age-related reduction in D-xylose absorption is caused by reduced renal function, and that intestinal absorption of D-xylose is not affected by aging. Descriptions of age-related changes in D-glucose absorption vary from one report to another, a discrepancy that seems attributable to different experimental methods.6 Bearing these discrepancies in mind, Hirata et al.' studied D-glucose absorption in young and old rats using two methods-everted intestine and purified brush border membrane vesicles (BBMV)-in order to determine which stage of D-glucose absorption shows age-related changes. First, everted gut sacs were used to measure D-glucose absorption by differences in electrical potential (Figure 2). In the old group, the half-saturation concentration was significantly higher than in the young group, a finding suggesting that the affinity of D-glucose to carrier molecules is reduced by aging. However, examination of D-glucose uptake in BBMV, purified by calcium precipitation, showed no difference in affinity (Figure 3). These results indicate that the age-associated reduction in affinity does not represent a change in the properties of the carriers themselves, but rather, an impairment caused by such factors as the distribution of carriers in the intestine or changes in the unstirred water layer. Fat Absorption Because fat is insoluble in water, its digestion and absorption within the digestive tract and the epitheNutrition Reviews, Vol. 50, No. 12
r **1
Young Old
Young Old
Figure 2. Age-related differences (mean *SD) in transmural electrical potential (in mV) induced by D-glucose in the presence of sodium (n = 5). Statistical significance indicated as follows: * p < 0.05; **p < 0.01.
lial cells of small intestinal mucosa require complicated mechanisms. Digestion and absorption of long-chain fatty acids, which comprise a majority of food components, involve the following steps: 1) formation of an emulsion in the stomach, 2) hydrolysis of triglycerides in the presence of pancreatic lipase, 3) formation of a complex micelle composed of bile acids, fatty acids, and monoglycerides; 4) diffusion of individual fatty acids through the microvillous membrane; 5 ) resynthesis of triglycerides in mucosal cells; 6) formation of chylomicrons; and 7) transfer of chylomicrons to lymph ducts. Each step occurs independently and is rate limiting. Because absorption of fatty acids is so complex, the influence of aging on this process is thought to be greater than its influence on absorption of other nutrients.8 Numerous studies' have investigated the effects of aging on fat absorption, and some have indicated that fecal fat excretion following excessive fat ingestion is increased in persons over 70 years of age. When '311-triolein and '"I-RISA were simultaneously loaded with a test meal, their digestion and absorption were normal in persons aged 60-79 years but were slightly reduced in those over 80 years. An 375
Immune Function
i'
A
0 Young
-
-
1.0
Y
0.5
E
Young
Old
2
Young
Old
Figure 3. Age-related differences (mean *SD) in D-glucose uptake by rat brush border membrane vesicles in the presence of sodium ( n = 4).
age-related reduction in palmitic acid uptake was observed in an experiment in which fat digestion and absorption were analyzed via 14C-palmitic acid uptake in rat intestinal mucosa. When intestinal lipids were analyzed by subsequent silica-gel thinlayer chromatography, the early stages of esterification of palmitic acid into triglyceride were reduced in the old group. These results suggested an age-related impairment of fat resynthesis within the intestinal mucosa. When the activity of enzymes catalyzing this resynthesis was examined, an age-related reduction in acyl CoA:monoglyceride acytltransferase was observed' (Table 1). We think that the age-related reduction in pancreatic lipase and bile secretion also may be involved in agerelated impairment of fat digestion and absorption. Table 1. Effect of Aging on Activity of the Enzyme Acyl-CoA:Monoglyceride Acyl Transferase
Group
n
Young Old
5 5
Total Microsomal Specific Protein (mg) Activity
Total Activity
*
9.58 2 5.71 6.06 k 1.03 74.57 32.42 7.36 t 2.51 3.30 5 1.69 20.40 k 7.16 D NS
