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Introduction
We recently summarized a 1997 review of anorexia in the elderly by Professor Morley, which cover the topic in general. The present article describes in more detail the age-related changes in feeding modulators, in particular those involving the cytokines.
Malnutrition is quite common in elderly people. While social, financial and psychological factors play important causative roles, there are physiological changes associated with the aging process which deserve attention.
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Anorexia in the elderly
Cholecystokinin (CCK) was first recognized as a satiating hormone 20 years ago. since then, multiple gastrointestinal hormones, such as amylin, gastrin-releasing peptide, glucagon, glucagon-like peptide and somatostatin have been shown to decrease food intake in animals and humans, probably by stimulating ascending vagus nerve fibers. In the central nervous system, monoamines (norepinephrine, serotonin), peptides (dynorphin, neuropeptide Y, corticotrophin releasing hormone, orexins) and nitric oxide can all modulate food intake. Finally, adipose cells produce leptin, another appetite-decreasing hormone.
It was formerly thought that deterioration in perception (taste, smell) was primarily responsible for lessened food intake in the elderly. More recently, age-related changes in the concentrations or efficacy of the feeding modulators have become preeminent. CCK plasma levels are raised in older persons, although this may be caused by malnutrition rather than aging per se. The kappa antagonist, dynorphin, has a decreased ability to drive food intake with age in rodents, and this may be the case in humans. Leptin levels may play a role in regulating anorexia in older men, but they seem to have no such effect in women. Nitric oxide has both a direct effect on the hypothalamus, and a relaxing effect on the fundus of the stomach; early satiation in older persons appears to be due, in part, to loss of this fundal response.
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The role of cytokines
Some of the conditions that are commoner in older persons - acute and chronic infections, chronic diseases, injuries, and neoplasms - are associated with elevated levels of immunoregulatory substances called cytokines. Each cytokine has multiple effects. Interleukin-1 (IL-1), for example, along with tumor necrosis factor (TNF), stimulates circulating leptin levels and produces anorexia; as secondary effects, it induces IL-6, which decreases food intake, and stimulates the excretion of corticotrophin-releasing factor (CRF), which in turn mediates suppression of food intake. Furthermore, IL-1 increases CCK plasma levels.
No differences in basal cytokine levels have been seen between young and old persons, but it seems likely that cells from aged subjects have a greater capacity to produce cytokines. Moreover, TNF may have a more powerful effect on feeding behavior in older persons.
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Cytokines and catabolism
Apart from their effects on appetite, cytokines are also associated with increased muscle protein breakdown during serious infections, injuries, and neoplasia. In addition, they are responsible for nitrogen loss, lipolysis, and lowered serum albumin levels. Elderly patients with idiopathic anorexia have been shown to have higher concentrations of IL-6 and TNF than healthy younger patients. Similarly, younger persons with anorexia nervosa have been found to have elevated levels of IL-6. However, whether cytokines cause anorexia, or vice-versa, has not yet been clarified. |
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Comment
Malnutrition in the elderly is a complex subject, requiring the astute physician to address a number of possible causes: the social situation, possible financial problems, psychological disorder, chronic disease, or neoplasm, all set against a background of so-called "normal" aging processes. As the effects of malnutrition in older persons can be so devastating, research into the roles of different internal modifying agents, like the cytokines, is a matter of priority. |
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