Am J C/in Nuir l992;55: 12035-75. Printed in USA. © 1992 American Society for Clinical Nutrition l203S

Changes in gastrointestinal function attributed to aging13

Robert M Russell

ABSTRACT There are numerous reports in the literature

ofimpaired gastrointestinal function with aging. However, most

gastrointestinal functions remain relatively intact because of the

large reserve capacity of the intestine, pancreas, and liver. Clin-

ically important changes in gastrointestinal function with aging

in human include decreased taste thresholds, hypochlorhydria

due to atrophic gastritis, and decreased liver blood flow and size.

Increased absorbability of lipids and large size molecules has

been demonstrated in aging animals, but this has not been studied

in humans. Nutrients with impaired gastrointestinal bioavail-

ability in aging include dietary B-12, calcium carbonate, and

ferric iron in atrophic gastritis; calcium, zinc, and possibly car-

bohydrate in a mixed meal. The implications of these changes

for health maintenance and chronic disease in elderly people

are in need ofstudy. Am J C/in Nuir l992;55:1203S-7S.

KEY WORDS Aging, elderly subjects, absorption, digestion,

gastrointestinal function, atrophic gastritis

Introduction

It is important to understand how aging affects the gastroin-

testinal tract because aging changes in this organ could affect

the nutritional requirements and medication dose needs of el-

derly people. There have been numerous reports in the literature

ofimpaired digestive and/or absorptive function with aging (I-

6). However, many of these studies were carried out in hospi-

talized or institutionalized elderly populations, and the gener-

alization of such results to a healthy elderly population is ques-

tionable. This review on gastrointestinal function with aging

concentrates mainly on human studies; animal studies are cited

only when human data are limited or lacking.

Taste, smell, and salivary function

The thresholds for recognition and detection offlavors become

elevated with aging (7-9). That is, a higher concentration of a

given tastant must be presented to an elderly person as compared

with a younger person before he or she can detect or recognize

it. Although taste detection thresholds are raised in elderly people,

this may not alter the perception of taste. The matter of how

food is perceived is influenced by other factors, including mcd-

ication, nutritional status, oral hygiene, and the state ofthe cen-

tral nervous system. It is not clear that smell is affected by aging

because definitive studies in humans have not been carried out.

The acinar cells of the salivary glands are reduced in number

in elderly people (10, 11). However, in humans, no linkage has

been demonstrated between aging per se and a reduction in eitherspontaneous or stimulated secretion of saliva ( 12- 14). Because

saliva is important to prevent mucosal dryness and to preventcaries, these issues are ofsome importance for the elderly person.

Studies that have suggested a decreased salivary function with

age have been confounded by factors such as disease and/or useof medication. Thus, it is probable that the fewer remainingsalivary acinar cells in old age are more efficient in their function.

Esophageal function

Clinically significant esophageal dysfunction is rare in all age

groups, including elderly groups, although some mild mano-

metric changes have been described (15). These include a de-

crease in the amplitude ofcontractions, a decrease in the number

of peristatic waves that occur after a swallow, and an increasein the number of disordered contractions in the body of theesophagus ( I 6- 18). One study has shown basal pressures and

post-edrophonium chloride injection pressures within the

esophagus to be significantly greater in young versus aged sub-

jects, suggesting a weakening of the esophageal smooth muscle

(1 8). Often, neurological diseases related to aging result in a

significant secondary esophageal dysfunction and can cause as-

piration pneumonia and malnutrition; but in general esophageal

function is a well-preserved nonpathological process, even in

advanced age.

Gastric function

Although reports are conflicting, emptying ofa standard mixed

meal from the stomach has been reported to be slowed with

aging (16, 19). For example, in one study, the time for emptyinghalf of a mixed meal in elderly persons was found to be 123 vs

50 mm in younger control subjects (20). On the other hand, the

I From the US Department ofAgriculture Human Nutrition ResearchCenter on Aging at Tufts University, and Tufts University School of

Medicine, Boston.2 This project has been supported with Federal funds from the US

Department of Agriculture, Agricultural Research Service under contract

number 53-3K06-5-lO. The contents ofthis publication do not necessarilyreflect the views or policies of the US Department of Agriculture, nor

does mention of trade names, commercial products, or organizationsimply endorsement by the US Government.

3 Address reprint requests to RM Russell, USDA Human NutritionResearch Center on Aging at Tufts University, 7 1 1 Washington Street,Boston, MA 02 111.

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1204S RUSSELL

total intestinal transit times did not differ between elderly andyounger control groups (21).

In rats, gastric acid secretion has been shown to decrease sig-nificantly with age both in the basal condition and in response

to fixed doses of exogenous gastrin (22). It has also been dem-onstrated that both basal and maximal gastric acid output de-crease in aging human populations (23); however, this is most

likely due to the inclusion of a subpopulation of elderly people

with atrophic gastritis. Atrophic gastritis has been reported to

increase in prevalence with aging, and � 40% of Bostonians overthe age of8O y are known to have this condition (24). Heliobacterpylon organisms, formerly considered as benign residents of the

upper gastrointestinal tract, have now been linked to the occur-rence of gastritis in aging. In a study recently reported by ourgroup, 80% of individuals over the age of 60 with mild to mod-crate gastritis had antibodies to H. pylon in their blood compared

with 50% of those who did not have gastritis (25). Such associ-

ations (although less strong) also have been reported by others(26), which supports the theory of a casual relation rather than

a simple colonization.As a result of atrophic gastritis, there is decreased secretion

of acid and intrinsic factor (27). However, the stomach withmild or moderate atrophic gastritis continues to secrete suffi-

cient intrinsic factor to prevent vitamin B-l2 malabsorption

by the usual mechanism (28). Thus, classic pernicious anemia

occurs rarely in the elderly person and appears only whencomplete atrophy ofthe gastric mucosa is present. Nevertheless,vitamin B-l2 has been shown to be malabsorbed in atrophicgastritis either because of inability to dissociate the vitamin

from food proteins, thus preventing its subsequent binding toR binders and intrinsic factor, and/or because of bacterial up-take ofthe vitamin in the stomach and proximal small intestine(27, 29, 30).

Atrophic gastritis may affect calcium bioavailability by limitingits ability to dissociate from food complexes (eg, fiber). Fur-thermore, calcium must be in solution for absorption to takeplace, and this process depends on acid (27). Recent evidence

shows that in people with severe atrophic gastritis or gastric atro-phy calcium is absorbed well when taken with food; however,calcium carbonate when taken alone has only limited bioavail-

ability in the absence of stomach acid (31).

It has been clearly demonstrated that the absorption of ferriciron is diminished in achlorhydric subjects (32). The beneficial

effect of acid presumably comes from keeping the ferric iron insolution until reaching the absorptive sites ofthe small intestine.Ferric iron is insoluble above pH 5 whereas ferrous iron and

heme iron remain in solution in neutral or slightly alkaline pHs(32, 33). Ligands such as ascorbic acid increase the solubility

and absorption of ferric iron at neutral or slightly alkaline pHs.However, the chelation with ferric iron occurs only when theiron is at an acid pH. In summary, both calcium and ferric ironare kept soluble, and hence, absorbable in the intestinal milieuthrough the acidifying effects of gastric acid.

Pancreatic function

Pancreatic function has been shown to diminish in older rats

as compared with younger animals (34). In older humans itappears that pancreatic secretion is not diminished upon initial

stimulation with either secretin or cholecystokinin (35). How-ever, upon repeated stimulation, pancreatic secretion drops sig-

nificantly lower in older persons as compared with younger con-

trol individuals (36). Thus, it appears that the pancreas mightbe able to function well under unstressed conditions. This wasconfirmed in a recent study by Arora et al (37), which showedthat fat malabsorption did not occur in elderly humans up tothe age of 91 y: 24-h fecal fat excretion on a diet of 100 g fat/dwas found to be 2.8 g for both age groups of 19-44 and 70-91.However, in a Swedish study, it was found that elderly volunteersdeveloped mild steatorhea when the dietary fat content was in-creased to rather uncharacteristically high levels of 1 15-120 g/d (38). In contrast, young volunteers did not develop steatorrheaon this amount of dietary fat. A similar situation was found fordietary protein in that aging humans developed an increasedfecal nitrogen excretion on protein diets of 1 .5 g . kg body

wt’ . d ‘ , whereas on a 1 .0 g level, both young and elderly sub-

jects had similar amounts of fecal nitrogen (38).Because pancreatic enzyme secretion is known to diminish

slightly with age, the question arises as to whether a high-fiber

diet might result in clinically significant steatorrhoea in elderlypeople. Pancreatic enzymes are known to be adsorbed to fiberand high-fiber diets aggravate the steatorrhoea in pancreatic-insufficient patients (39). Our laboratory studied the effect of a

low-fiber diet (10 g/d) and a higher-fiber diet (35 g/d) on fecal

fat excretion in elderly individuals consuming 100 g fat/d for 6d. Fecal-fat collections were made on the last 3 d of the study.Fecal fat excretion rates in the elderly subjects while taking thelow-fiber diet was 3.0 vs 2.9 g/d on the high-fiber diet (Table 1).Thus, it appears that fiber does not contribute to steatorrhea in

aged individuals through this range of fiber intake.With regard to carbohydrate digestion and/or absorbtion, a

study was conducted by Feibusch and Holt (40), which was in-

terpreted as showing decreased carbohydrate digestive or ab-

sorptive capacity with aging. Mixed carbohydrate meals con-

taming � 200 g of carbohydrate were fed to elderly individualsand young control subjects. Breath-hydrogen tests were subse-quently carried out, and in the elderly group the prevalence ofpositive breath-hydrogen tests was �60% on the 200-g carbo-hydrate meal. In the young control group there were no positive

breath-hydrogen tests, even on the 200-g carbohydrate meal.Breath-hydrogen tests become positive when the carbohydrateis exposed to bacteria. Therefore, the high prevalence of positive

breath-hydrogen tests in the elderly group could be due to car-bohydrate maldigestion and/or malabsorption with exposure of

TABLE 1

Fecal-fat levels in elderly subjects on low- and high-fiber diets

Subject Low fiber High fiber

g/d

I23

45

67

89

4.0

2.83.38.31.4

2.50.4

2.12.2

1.8

1.62.6

3.72.6

3.54.6

2.33.4

i+SEM 3.0±0.8 2.9 ±0.3

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the carbohydrate to colonic bacteria. Alternatively, positive

breath-hydrogen tests could be due to exposure of the carbo-

hydrate to small-intestinal bacterial flora. Detailed studies of

small-bacterial intestinal bacterial flora in elderly human beingshave not been carried out. Thus, whether carbohydrate is mal-

digested or malabsorbed in the elderly human remains uncertain.

Gallbladder function

It is clear that the prevalence ofgallstones rises with age (41).

The emptying of the gallbladder has been studied by severalgroups, and in one study, Khalil et al (42) found that fasting

and stimulated concentrations of cholecystokinin in plasmawere higher in older individuals than in younger volunteers.However, fasting and contracted gallbladder volumes were

equal in both age groups, as was the rate of gallbladder emp-tying. Although the gallbladders of the elderly people showed

earlier initiation of contraction, it appears that the sensitivity

of the gallbladder to cholecystokinin stimulation may be de-

creased in older people (42).

Liver function

The issue of how aging effects liver function is extremely im-portant because elderly people are the most medicated segmentof society and many medications are processed and excreted by

the liver. Clinical studies have shown that the rate of disposition

of various medications declines with age. However, the mech-

anisms to explain this have not been well studied in humans.

Liver size decreases with age and portal blood flow also decreases

significantly with age; these features by themselves could account

for the decrease in drug elimination seen in the elderly person(43, 44). For example, in one study, portal blood flow in humans

< 40 y old was shown to be 740 vs 595 mL/min in those over

age 71 (43).

In rats it has been shown that certain cytochrome p450 en-zymatic activities (eg, microsomal NADPH cytochrome reduc-

tase) are decreased as a function ofthe animal’s age (45). How-

ever, there also appears to be a qualitative change in the above

enzyme due to posttranslational modifications in conformation

(45). The aminopyrine breath test measures the rate of demeth-

ylation of aminopyrine by the liver and estimates hepatic mi-

crosomal capacity. It has been reported that demethylation ca-

pacity for aminopyrine is inversely related to age in humans

(46). However, other studies have been unable to show direct

age-related changes in phase 1 drug metabolizing enzymes (37,

47). Phase 2 drug metabolism studies (eg, glucuronic acid con-

jugation, glutathione conjugation) have shown variable results,depending on the animals used and the particular enzymes stud-

ied (48). Human investigations on liver function have shown a

decrease in sulfobromophthalein (BSP) and galactose elimination

capacity by the aged liver although the mechanisms, once again,

are uncertain (49, 50). Routine liver chemistries do not change

with aging, although serum albumin shows a slight fall, which

apparently is not related to poor protein nutriture (5 1, 52). The

effects of aging on liver function are summarized in Table 2.

Small intestinal function

Mucosal surface area has been reported to be slightly dimin-ished in the aging human versus the younger human (53). How-

TABLE 2

Effect of aging on liver physiology

Liver variable Aging effect

Liver size DecreasedHepatic blood flow DecreasedBSP, galactose elimination DecreasedMicrosomal drug metabolism Normal to decreased

Glucuronidation Probably unchangedGlutathione . May be decreasedSerum albumin Slightly decreasedRoutine liver chemistries Normal

ever, Corazza et al (54) reported that ratios ofmean surface area

to volume ofjejunal mucosa are not different in geriatric patients

versus younger subjects. A series ofstudies in animals have shown

an age-related increase crypt cell proliferation of the small in-testine, as well as decreased activity of several small intestinalbrush border enzymes (eg, lactase, maltase, sucrase-isomaltase)

(55, 56). Such findings might be applicable to humans.

Guth (57) demonstrated a decline in D-xylose urinary excretionafter a 25-g load with advancing age, especially after the age of80. Further, a decline of blood levels of D-xylose occurred only

after the age of 80. Studies have concluded that the decreased

urinary excretion of D-xylose seen in advancing age is due todeteriorating renal function rather than deterioration of small

intestinal absorptive function, at least up to the age of 80 (36,

57). It is clear that when the D-xylose test is used to diagnose

malabsorption it can only be interpreted in the older person if

concurrent data on renal function are also known.

The question ofwhether increased numbers ofbile salt splitting

bacteria reside in the small intestine of elderly versus younger

people has been examined by us, and we were unable to findevidence for overgrowth of the small bowel by such bacteria(37). This is in agreement with the finding that there is no de-

monstrable increase in fat malabsorption in normal elderly versus

younger people on physiological diets. As mentioned previously,

protein malabsorption also does not occur with advancing age

if normal diets are being eaten. However, it has been shown by

Navab and Winter (58), in in vitro studies in rat everted gut

sacs, that the absorption ofaromatic amino acids is diminished

with age. The significance ofthis is questionable due to the largereserve capacity ofthe small intestine because ofits length. That

is, even if a diminished absorptive capacity for certain amino

acids can be shown to occur over a segment of bowel, when the

entire length ofbowel is taken into account, the reserve capacity

is so great that no malabsorption occurs.

Hollander et al (59) and Hollander and Morgan (60) showed

that vitamin A and fatty acid absorption increases with advancingage in the rat. They attributed this to a change in thickness orcharacter of unstirred water layer overlying the epithelial cellmembrane. In humans, vitamin A tolerance tests using physi-

ological doses ofvitamin A have shown higher peak heights andareas under the timed curves ofblood retinyl ester levels in elderly

versus younger adults (6 1 ). However, when these subjects were

infused with vitamin A-laden chylomicron-rich plasma, the el-derly individuals were also found to have a decreased clearanceability by the liver for the chylomicron remnants containing

vitamin A esters compared with the younger control subjects.

Thus, it appears that the higher tolerance curves in elderly versus

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1206S RUSSELL

younger control subjects can be explained at least in part by the

decreased clearance capacity of the liver for chylomicron rem-

nants, rather than increased absorptive ability by the small in-testine.

It is interesting that a study showed increased permeability ofthe aging small intestine to medium-sized polyethelene glycol(PEG 900) by using everted sacs of rat intestine ranging in age

from 5 to 102 wk (62). This study seems to show that the agingrat intestine has less ability to exclude large-size molecules frompenetrating the intestinal mucosa, allowing, for example, mu-

tagenic or antigenic compounds to enter the body. The role of

decreased intestinal blood flow in producing these changes has

yet to be studied.

Metal malabsorption has been studied in the human vis-#{224}-viszinc, calcium, iron, and copper. Although zinc absorption isdiminished in elderly versus younger individuals, excretion ap-

pears to be diminished in elderly subjects, in that zinc balancedid not differ between elderly and younger subjects on the same

diets (63). Calcium absorption declines with age (64) and calcium

and iron absorption are both influenced by gastric atrophy asnoted above. However, in addition, the elderly human smallintestine appears to be less able to adapt to a lower calcium diet

than does the younger person’s intestine (65). That is, youngersubjects are able to increase the efficiency ofcalcium absorptionwhen exposed to a low-calcium diet whereas older subjects areless able to make this adaptation. Copper absorption appearsnot to be significantly affected by age (66).

Colonic and anal/rectal function are not considered in thisreview because recent reviews are available (67). In the past de-cade we have learned much about how aging effects the physi-ological function of the gastrointestinal tract. The implication

ofthese changes for health maintenance and chronic disease areas yet uncertain. Thejob ofthe next decade is to delineate whichof these physiological changes have significant health and/or

disease implications and by what means negative physiologicalchanges can be delayed or their impact diminished. U

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