Aging and the Gastrointestinal System

Normal Physiology of Aging

With a few notable exceptions, the digestive system maintains normal functioning in older adults. To distinguish between the expected age-related alterations of the gut and symptoms attributable to pathologic conditions, the clinician must have an understanding of the normal physiology of aging. One must also appreciate the interactions between the gastrointestinal (GI) tract and long-standing exposures to environmental agents (e.g., medications, tobacco, alcohol) and chronic non-GI disease states (e.g., congestive heart failure, diabetes mellitus, chronic obstructive pulmonary disease [COPD], dementia, depression). With this knowledge, it will become apparent that most new GI complaints in otherwise healthy older adults are due to disease rather than to aging alone and therefore merit appropriate investigation and treatment.

Aging is not associated with a difference in the desire to eat or the hunger response prior to meal intake, but postprandial hunger and desire to eat are reduced. One explanation may be that fasting and intraduodenal lipid-stimulated plasma concentrations of cholecystokinin (CCK), a physiologic satiety factor; leptin, a hormone that functions mainly as a signal of adiposity eliciting long-term satiety; and GLP-2, an incretin hormone mainly released by the L cells of the distal small intestine in response to nutrient ingestion, have been found to be higher in older than in younger men. In addition, ghrelin, a growth hormone–releasing peptide from the stomach that functions as a potent stimulator of energy intake, is one-third lower in older adults. However, anorexia in older adults should not be attributed to advanced age alone. This symptom warrants evaluation to exclude a medical or psychological cause or a medication-induced adverse effect.

Up to 40% of healthy older adults subjectively complain of dry mouth. Although baseline salivary flow probably decreases with aging, as noted with decreased salivary bicarbonate (involved in neutralization of refluxed acid), stimulated salivation is unchanged in healthy and edentulous geriatric patients. Chewing power is diminished, probably because of decreased bulk of the muscles of mastication, although perhaps attributable in part to preclinical manifestations of neurologic disease rather than to the normal aging process. Although many older patients are edentulous to some degree, better dental care has now enabled more of them to have intact teeth than in the past.

Gustatory and olfactory sensation tend to decrease with aging. The ability to detect and discriminate among sweet, sour, salty, and bitter tastes deteriorates as one gets older. Thresholds for salt and bitter taste show age-related elevations, whereas that for sweet taste appears stable. Olfaction decreases dramatically following the fifth decade of life, frequently resulting in anosmia after the age of 90 years, when the olfactory threshold increases by about 50%, contributing to poor smell recognition. Increasingly, chronic diseases observed during aging (Alzheimer or Parkinson diseases) may be responsible for such a decline, and recent studies have focused on the sensation of smell as a predictor of disease presentation.

Despite early data to the contrary, the physiologic function of the esophagus in otherwise healthy individuals is well preserved with increasing age, with the exception of very old patients. Studies from the early 1960s introduced the concept of the term presbyesophagus, based on cineradiographic and manometric data, but the term has been abandoned. Other studies study that excluded patients with diabetes or neuropathy found no increase in dysmotility in older men. Investigators have also found that minor alterations may occur in some octogenarians, including decreased pressure and delayed relaxation of the upper esophageal sphincter and reduction in the amplitude of esophageal contraction. Furthermore, one study has shown that age-related changes of increased stiffness and reduced primary and secondary peristalsis in the human esophagus is associated with a deterioration of esophageal function beginning after the age of 40 years. In addition, in a study comparing esophageal manometry and scintigraphic examinations of gastroesophageal reflux in groups of healthy volunteers ranging from 20 to 80 years of age, it was determined that although the number of reflux episodes per volunteer was similar in the various age groups, the duration of reflux episodes was longer in older volunteers. The older participants had impaired clearance of refluxed materials due to a high incidence of defective esophageal peristalsis. Similarly, in another study, age was shown to correlate inversely with lower esophageal sphincter (LES) pressure and length, upper esophageal sphincter (UES) pressure and length, and peristaltic wave amplitude and velocity, suggesting that normal esophageal motility deteriorates with advancing age. It was also noted that hiatal hernias are more common with increasing age and are found in up to 60% of patients older than 60 years. Together, these findings may help explain the high prevalence of reflux symptoms in older adults.

Most studies on gastric histology have found evidence of an increased prevalence of atrophic gastritis in people older than 60 years. Consequently, it has been suggested that aging results in an overall decline in gastric acid output. However, more recent data have demonstrated that gastric atrophy and hypochlorhydria are not normal processes of aging. Rather, Helicobacter pylori infestation, which is more common in older adults, not advancing age itself, appears to be the more likely cause of these histologic and acid secretory changes. The literature remains conflicted over the issue of whether aging alone, rather than factors such as increased H. pylori infestation and decreased smoking, leads to altered pepsin secretion. However, given recent trends, many older adult patients also retain their acid secretion ability in old age as a result of increased H. pylori treatment and cure. This can in turn raise the risk for reflux symptoms, given the peristaltic dysfunction associated with aging. Data are scarce in relation to gastric motility, emptying, and gastroduodenal reflux and their relationship to gastric function and acid production. Intrinsic factor secretion is usually maintained into advanced age and is retained longer in the setting of gastric atrophy than acid or pepsin secretion. Gastric prostaglandin synthesis, bicarbonate, and nonparietal fluid secretion may diminish, making older adults more prone to nonsteroidal inflammatory drug (NSAID)–induced mucosal damage. Finally, most (but not all) studies have shown that gastric emptying of solids remains intact in older adults, although liquid emptying is prolonged.

Small bowel histology and transit time do not appear to change with age in humans, although increased epithelial proliferation in response to cellular injury has been found in a rodent model. Splanchnic blood flow is reduced in older adults. Small bowel absorptive capacity for most nutrients remains intact, but there are some exceptions, especially those due to effects of disease (e.g., chronic gastritis, bacterial overgrowth) and medications on micronutrient absorption. However, the increase in small bowel bacterial overgrowth seen in older adults may be attributed to medications (slow gut transit), diseases such as diabetes, and mobility impairment, which lead to malnutrition and changes in gut immune function, and not to advancing age. No change with aging was found in duodenal brush border membrane enzyme activity of glucose transport. d -Xylose absorption testing remains normal after correction for renal impairment, except perhaps in octogenarians. Jejunal lactase activity decreases with age, whereas that of other disaccharides remains relatively stable, declining only during the seventh decade. Protein digestion and assimilation and fat absorption remain normal with aging, although the latter has a more limited adaptive reserve capacity. Absorption of fat-soluble vitamin A is increased in the older adult population, whereas vitamin D absorption may be impaired, and a reduction in vitamin D receptor concentration and responsiveness occurs. Absorption of the water-soluble vitamins B ₁ (thiamine), B ₁₂ (cyanocobalamin), and C (ascorbic acid) remains normal, whereas disparate data exist on folate absorption with aging. Iron absorption is maintained in healthy older adults who are not hypochlorhydric, but absorption of zinc and calcium declines with age.

Several histologic changes have been demonstrated in the colon, including increased collagen deposition, atrophy of the muscularis propria, with an increase in the amount of fibrosis and elastin and an increase in proliferating cells, especially at the superficial portions of the crypts. Some studies have found that colonic transit time increases with aging to varying degrees, perhaps due to the increase with age in the number of abnormally appearing myenteric ganglia in the human colon, resulting in myenteric dysfunction, whereas others have not shown any change. Prolonged transit time in older adults with constipation is due to factors associated with aging (e.g., comorbidity, immobilization, drugs) rather than to aging per se. It is currently believed that colonic motility and the colon's response to feeding are largely unaffected by healthy aging; however, conditions such as pelvic floor dysfunction and impaired rectal sensation and poor distention all contribute to impaired colonic function and altered bowel habits.

Anorectal physiologic changes have been well documented. Aging is associated with decreased resting anal sphincter pressure in men and women and decreased maximal sphincter pressure in women. This may be due in part to age-related changes in muscle mass and contractility and in part to pudendal nerve damage associated with perineal descent in older women. The closing pressure—that is, the difference between the maximum resting anal pressure and rectal pressure—also falls in older women. Maximum squeeze pressure declines with age, particularly in postmenopausal women, as does rectal wall elasticity. An age-dependent increase in rectal pressure threshold producing an initial sensation of rectal filling has also been demonstrated. The combined effects of reduced rectal compliance, sensation and perineal laxity may be the predisposing factors to fecal incontinence in older women. Defecation dynamic studies in older women have shown a significant failure of rectal evacuation because of insufficient opening of the rectoanal angle and an increased degree of perineal descent compared with younger women. Histologic and endosonographic studies on anorectal structure have revealed that the internal anal sphincter develops fibrofatty degeneration and increased thickness, respectively, with aging.

The pancreas undergoes minor histologic changes with aging. There also appears to be a steady increase in the caliber of the main pancreatic duct, with other branches showing areas of focal dilation or stenosis, without any apparent disease or functional age-related changes In fact, 69% of patients older than 70 years without pancreatic pathology have a so-called dilated duct when criteria developed for younger patients are applied. However, any duct larger than 3 mm should be regarded as pathologic. High echogenicity of the pancreas is a normal finding on ultrasonography. Aging reduces exocrine pancreatic flow rate and secretion of bicarbonate and enzymes, and the rate falls significantly with repeated stimulation. However, other studies have shown a lack of reduced pancreatic secretions with age, independent of disease and the effect of drugs. Given that a variable degree in functional reserve of different organ systems occurs in the aging process, it is not clearly known whether pancreatic insufficiency occurs as a sole consequence of aging.

Anatomic studies on the liver reveal an age-related decrease in weight, both absolute and relative to body weight, as well as the number and size of hepatocytes. Pseudocapillarization of the hepatic sinusoid (morphologic changes such as defenestration and thickening of the liver sinusoidal endothelial cell, increased numbers of fat-engorged, nonactivated stellate cells), lipofuscin accumulation, bile duct proliferation, fibrosis, and nonspecific reactive hepatitis are histologic changes more common in older adults. The major functional changes in older adult patients are reduction in hepatic blood flow, altered clearance of certain drugs, and delayed hepatic regeneration after injury. The altered drug clearance is due to age-related reductions in phase I reactions (e.g., oxidation, hydrolysis, reduction), first-pass hepatic metabolism, and serum albumin–binding capacity. Phase II reactions (e.g., glucuronidation, sulfation), however, remain unaffected by aging. There are no age-specific alterations in conventional liver blood test results.

Although a cholecystographic study found that gallbladder emptying remained stable with increasing age, other studies have shown that gallbladder contraction in older adults may be less responsive to CCK. Increases in the proportions of the phospholipid and cholesterol components of bile raise the lithogenicity index, leading to an increased occurrence of gallstones in older adults. Furthermore, the decline in bile salt synthesis, deconjugation of bile salt pigments, and increase in bactobilia are all speculated as being factors in the increased incidence of gallstone disease. Choledocolithiasis is particularly common; in older adult patients who have undergone an emergency cholecystectomy, the incidence of bile duct stones approached 50%. Even in the absence of bile duct stones or other pathology, older adult patients generally have larger common bile duct diameters than younger patients.