Journal of Gerontology: MEDICAL SCIENCES

2003, Vol. 58A, No. 2, 131137

Copyright 2003 by The Gerontological Society of America

Editorial
Anorexia and Weight Loss in Older Persons
John E. Morley
Division of Geriatric Medicine, Saint Louis University School of Medicine, and Geriatric Research, Education,
and Clinical Center, VA Medical Center, St. Louis, Missouri.

NINTENTIONAL weight loss represents a cardinal

U
symptom of frailty in older persons (16). Even a small
decline in body mass in older persons is associated with
mortality (7). Protein energy malnutrition is associated with
anemia, pressure ulcers, sarcopenia, bone loss and hip
fractures, declining immune function, impaired immune
response to vaccinations, infections, cognitive impairment,
functional decline, and poor quality of life (817). Weight
loss is a sentinel event in long-term care facilities and associated with particularly poor outcomes (18,19). Despite
this, aggressive nutritional management when weight loss
is well established is often not associated with improved
outcomes (2024). For this reason, it is important that
geriatricians increase their understanding of the pathophysiological processes that underlie weight loss in older persons
(25) and increase their vigilance to detect early weight loss
and institute-appropriate preventive and health promotion
measures (26,27).
In this issue of the Journals, Paquet et al. (28)
demonstrate the importance of emotional state on food
intake in older persons undergoing geriatric rehabilitation.
Positive emotions at the time of eating increased food
intake, while anxiety, depression, and anger had negative
effects on food intake. While previously depression has
been shown to have a major negative effect on food intake
(29,30), this study extends these findings to demonstrate that
much smaller fluctuations of mood at the time of the meal
produce major effects on the amount of food ingestion.
de Castro (31) found that, in older persons living in the
community, social facilitation at mealtimes and palatability
were major factors in the amount eaten. He suggested that
increasing the number of people present at a meal could
enhance food intake. This was found to be true in persons
receiving Meals on Wheels by Suda et al. (32), who found
that when the meal deliverer stayed while the meal was
eaten, nutritional risk and dysphoria were decreased.
When staff members spend more time feeding residents in
the nursing home and utilize more verbal and physical
prompts, food intake increased (33). Under these circumstances, it took an average of 38 minutes to feed a resident

compared to 9 minutes under usual conditions. Because of

the importance of food intake, it is critical that nursing staff
are trained to be able to make accurate estimations of calorie
intake in older persons (34).
Enhancing the environment in which meals are eaten has
been shown to improve food intake (32). Older persons eat
more in the morning (31), and this circadian shift is even
more marked when they develop cognitive impairment (35).
Thus, it is recommended that older persons receive more
food at breakfast (36). Increasing palatability of meals later
in the day also improves food intake (37). For these reasons,
the Clinical Guide to Prevent and Manage Malnutrition in
Long-Term Care provides a number of hints to improve
social facilitation of eating at mealtime (38).
It has been suggested that weight loss is more likely to
occur in older persons who are lifelong practitioners of
dietary restraint, i.e., the intentional restriction of food
intake to prevent weight gain (39,40). In some older
persons, this has been associated with recurrence of
anorexia nervosa toward the end of their life. In a normalweight older population, Bathalon et al. (41,42) found no
major differences between persons who practiced dietary
restraint and those who did not. They did, however, have
lower hemoglobin levels. Lower hemoglobin levels have
been associated with an increase in frailty (43). Some older
persons, when made aware of the studies on caloric
restriction and longevity in animals, excessively restrain
their food intake and develop malnutrition (4448).
Similarly, malnutrition is seen in older persons attempting
to lower their cholesterol to prevent heart disease. This
condition is known as cholesterol phobia (49). In 1988,
we suggested that there was a physiological anorexia of
aging that universally affected all older persons (50). The
existence of a decline in caloric intake over the life span is
now well established by multiple epidemiological studies
(51). We postulated that this age-related physiological
anorexia placed older persons at particular risk for developing malnutrition when they developed a disease process. Roberts et al. (52) showed that older persons had
a deregulation of feeding regulation such that they struggled
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No fear can stand up to hunger, no patience can wear it out, disgust simply does not exist where
hunger is...Its really easier to face bereavement, dishonour and perdition of ones soul than this
kind of prolonged hunger.
Heart of Darkness, Joseph Conrad

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Figure 1. Appetite regulation. MCH 5 melanin concentrating hormone; NPY 5 neuropeptide Y; CRF 5 corticotropin-releasing factor; AGRP 5 agoute-related
peptide; CART 5 cocaine-amphetamine-regulated transcript; CCK 5 cholecystokinin; GLP-1 5 glucagon-like peptide-1; GRP 5 gastric-related peptide; PYY 5
peptide YY; TNF 5 tumor necrosis factor; IL 5 interleukin; NO 5 nitric oxide.

to alter their food intake either upward or downward in

response to perturbations of body mass. Over the last
decade, much research has explored the factors involved in
the physiological regulation of food intake (53,54). As we
originally postulated in the early 1980s, much of the normal
feeding system is redundant, with multiple fail-safe

mechanisms to ensure that hunger and the desire to intake

continues and, therefore, that the individual survives (55).
The development of the physiological anorexia of aging
appears to be predominantly due to altered gastric signals
resulting in early satiation (56). With aging there is
a decrease in the ability of the fundus to accommodate

EDITORIAL

Table 1. MEALS-ON-WHEELS Mnemonic for

Reversible Causes of Weight Loss
Medications (e.g., digoxin, theophylline, cimetidine)
Emotional (e.g., depression)
Alcoholism, elder abuse, anorexia tardive
Late life paranoia
Swallowing problems
Oral problems
Nasocomial infections (tuberculosis, clostridium difficile, helicobacter pylori)
Wandering and other dementia-related behaviors
Hyperthyroidism, Hypercalcemia, Hypoadrenalism, Hyperglycemia
Enteral problems (e.g., gluten enteropathy)
Eating problems
Low salt, low cholesterol, and other therapeutic diets
Stones (cholecystitis) and shopping problems

cancer and end-stage heart disease can lead to the cancer

anorexia-cachexia syndrome and the cardiac cachexia
syndrome, respectively (9092). Cachexia is derived from
the Greek words kakos meaning bad and hexis meaning
condition. The development of these cachexia syndromes
appears to be related to the release of cytokines by the
diseased tissues (93). Tumor necrosis factor a, interleukin-1,
interleukin-6, and ciliary neurotropic factor appear to be
particularly potent cytokines responsible for anorexia,
muscle mass loss, and low albumin levels (94,95).
Cytokines decrease albumin levels by decreasing production
of albumin and producing extravariation of albumin outside
of the intravascular space (9597). In addition, cytokines
activate nuclear factor kappa B, which reduces the
formation of Myo D, and thus decrease muscle repair
(98). Cytokines can produce their effects peripherally on
multiple tissues, but they also produce effects on the central
nervous system either directly by crossing the blood-brain
barrier or secondarily by stimulating ascending fibers of the
autonomic nervous system (99).
The majority of pathological causes of weight loss are
reversible. For the clinician, these causes are easily
remembered by using the MEALS-ON-WHEELS mnemonic (Table 1; 100). Depression is the major reversible
cause of weight loss (28,30,101). Therapeutic diets remain
a common cause of weight loss, and their utility in older
persons, particularly those in nursing homes, continues to
be of questionable value (102104). If caloric supplements
are to be used, they should be administered at least 1 hour
before the meal or their major effect is mainly to reduce the
size of the meal the elderly person would have eaten (105).
There is increasing enthusiasm for the use of orexigenic
agents in the treatment of anorexia and weight loss in older
persons. Megestrol acetate increases weight in older persons
(106,107) most probably by decreasing cytokine production.
Unfortunately, this is associated with a decline in testosterone levels, resulting in a decline in lean mass while increasing fat mass (108, and see 109 in this issue of the
Journal). Testosterone can increase muscle mass in older
persons (110,111), and its decline with aging is associated
with a decline in muscle mass, strength, and functional
status (112,113). Testosterone replacement may enhance
function in older persons during rehabilitation (114).

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large volumes of food (57). This appears to be due to the

failure of food in the fundus to release nitric oxide, resulting
in a failure of smooth muscle relaxation (58,59). This
leads to early antral filling, resulting in satiation signals
being generated as the antral diameter increases (60,61).
In addition, cholecystokinin, a gastrointestinal peptide that
decreases hunger, circulates in higher levels in older
compared to young persons (62,63) and is a more potent
anorectic agent in older humans and other animals (64,65).
The role of antral nervous system neurotransmitters with
aging is less clear and based predominantly on studies in
rodents. The kappa opioid receptor modulator, dymorphin,
has been shown to be less effective at increasing food intake
in older rodents (66). However, a study in humans failed to
demonstrate a clear effect of altered opioid tone in the
pathogenesis of the anorexia of aging (67). Neuropeptide Y
(NPY) is an important orexigenic agent. Older animals
maintain their responsiveness to NPY stimulation of food
intake (68), but have a reduction in NPY gene expression
in response to starvation in older animals (69). Within the
central nervous system, nitric oxide appears to play an
important coordinating role in the production of feeding
due to a variety of orexigenic neuropeptides such as orexin,
neuropeptide Y, ghrelin, and agouti-related peptide (70,71).
There is evidence that, with aging, there is a decline in the
efficacy of the nitric oxide-synthesizing mechanisms related
to feeding (59).
Leptin (from the Greek for thin) is a peptide hormone
produced by adipose cells that results in a decreased food
intake and an increase in metabolic rate (72). With aging in
men, there is a decline in testosterone levels (7375), and
this is associated with an increase in leptin levels out of
proportion to fat loss in older males (76,77). However,
another study failed to show a correlation between leptin
levels and involuntary weight loss in older humans (78).
This may be due, in part, to the development of leptin
resistance with aging (79). In older animals, testosterone
deficiency is associated with an increase in the anorectic
peptide, cocaine-amphetamine-regulated transcript (CART)
peptide, and a decrease in NPY, which could be reversed by
the administration of testosterone (80).
Recently ghrelin, an orexigenic peptide produced by the
fundus of the stomach, has been isolated (81). Its feedingenhancing effects are antagonized by a metabolite of peptide
YY, PYY336 (82). Peptide YY has been shown to produce
weight loss when administered peripherally (83). Ghrelin
also produces growth hormone release, which has been used
to treat malnutrition in older persons (84,85). These agents
may well prove to be important mediators of the gastricinduced satiation component of the anorexia of aging. The
complex interactions of these neurotransmitters in the
pathophysiology of the anorexia of aging are outlined in
Figure 1. However, as pointed out in the pages of the
Journals, long-term use of growth hormone is unlikely to
enhance longevity (8688).
As so eloquently attested to by Blumenthal (89) in a recent
issue of the Journals, the aging-disease dichotomy is often
an inseparable conundrum. This is particularly true when
anorexia and weight loss are accelerated in older persons
when they develop one or more disease processes. Thus,

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Figure 2. Potential pharmacological approaches to treatment of anorexia and weight loss in older persons. NPY 5 neuropeptide Y; CRF 5 corticotropin-releasing
factor; NSAIDS 5 nonsteroidal anti-inflammatory drugs; CCK 5 cholecystokinin; PYY 5 peptide YY.

EDITORIAL

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Appetite stimulation and a feeling of general well-being

are well-recognized effects of marijuana (115). Dronabinol,
a cannabis derivative, is available and has been shown to
enhance appetite and mood in patients with end-stage
dementia, cancer, and AIDS (116118). This agent can also
inhibit vomiting and decrease pain, making it an excellent
agent for use in end-of-life care (119). This drug appears to
produce its effect through the endogenous CB1 cannabinol
receptor. The function of endogenous cannabinoids is regulated by leptin (120).
The effects of the antiserotonergic agent, cyproheptadine,
have been disappointing. Thalidomide inhibits cytokine
release and may prove to be an excellent agent for treatment
of cachexia syndromes (121). An approach to the development of drugs for the anorexia of aging is given in
Figure 2.
Weight loss is considered a sentinel event in nursing
homes. Enormous strides have been made in the understanding of weight loss and anorexia over the last decade.
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are at nutritional risk are detected, the guidelines for
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