Workshop: anorexia during disease—from research to clinical practiceAnorexia, sarcopenia, and aging☆
Introduction
With aging there is a decline in food intake.1 This occurs to a greater extent in men than women. This decline in food intake also is seen when the food intake of very healthy older persons is examined.2 We have termed this physiologic decline in food intake the anorexia of aging. This decline in food intake with aging has multiple causes including an increase in the activity of the peripheral satiation system and a decline in the activity of the central feeding system.
The decrease in food intake coupled with a decrease in exercise leads to a decline in muscle mass (sarcopenia). This physiologic anorexia of aging also makes older persons more vulnerable to developing severe anorexia and muscle wasting when they develop disease. This condition is known as cachexia, from the Greek kakos ’bad’ and hexis ’condition.’ However, the pattern of weight loss seen with cachexia differs from that seen with pure nutrient deficiency, suggesting that other factors also are involved in producing protein catabolism and muscle wasting.
Section snippets
Peripheral satiating systems
Taste thresholds increase with aging and olfaction declines. These changes can be particularly dramatic when the older person takes medications. In addition, zinc deficiency, which can occur with a variety of diseases such as diabetes, can further elevate the taste threshold.3 However, despite these changes, altered hedonic values appear to play a minor role in the anorexia of aging.4
The stomach is a major player in producing the early satiation often seen in older persons. With aging there is
Growth hormone
Growth hormone and insulin growth factor-1 decline in older persons.13 Insulin growth factor-1 has been shown to have more dramatic decreases in malnourished persons.14 Growth hormone is an anabolic hormone that also increases food intake. Growth hormone has been shown to reverse catabolism in older malnourished persons.15 However, a recent study in critically ill malnourished subjects suggested that growth hormone increases mortality.16
The central nervous system
Multiple anatomic connections within the central nervous system are involved in modulating food ingestion. These connections include the amygdala, nucleus accumbens, nucleus tractus solitarious, and the hypothalamus. Within the specific nuclei in these regions, multiple neurotransmitters interact with one another to form the “feeding cascade.”17, 18
Animal studies have supported a role for decreased dynorphin stimulation of feeding in the pathophysiology of the anorexia of aging.19, 20 Dynorphin
Testosterone, leptin, and sarcopenia
Testosterone levels decline with aging in males.32, 33 As sex-hormone-binding globulin levels increase with age, there is an even more dramatic fall in free or bioavailable testosterone.34, 35 This decline in testosterone has been shown to be the major factor associated with the decline in muscle mass and muscle strength that occurs with aging.36 In addition, it is associated with a decline in functional status, i.e., the ability to perform simple tasks necessary for the maintenance of the
Cytokines, aging, and weight loss
As people age, they develop numerous minor ailments (e.g., arthritis, recurrent infections, tumors, and pressure ulcers) that result in inflammatory responses. Such inflammatory responses result in the elaboration of cytokines. Elevated cytokines, especially interleukin (IL)-6, have been associated with a decline in function and frailty in older persons.48, 49 The mechanisms by which cytokines do this are not clear but include anorexia and muscle protein catabolism, resulting in weight loss and
Pathologic anorexia and weight loss
As alluded to in the section on cytokines, disease is a major cause of protein-energy malnutrition. Whereas cancer is an obvious cause of anorexia, recent studies have shown that malnutrition in most older persons has treatable causes.47 Weight loss in older persons can be caused by anorexia, increased metabolism (e.g., hyperthyroidism), and malabsorption (e.g., gluten enteropathy). Depression is the most common cause of weight loss in older persons.63, 64 In general, the more severe the
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- ☆
Appearing in this issue of Nutrition is the third segment, consisting of three papers, of a four-part special series highlighting work presented at the Anorexia During Disease—From Research to Clinical Practice Workshop held recently in Ascona, Switzerland. The Workshop was organized by Wolfgang Langhans, DVM, PhD. Professor Langhans is also Guest Editor of this series. The final segment of this series is planned for the November/December issue of Nutrition. —Editor