REVIEW

CURRENT
OPINION Anorexia of aging and its role for frailty
Angela M. Sanford

Purpose of review
The purpose of this review is to examine the concept of anorexia of aging, including its complex
pathophysiology and the multifaceted interventions required to prevent adverse health consequences from
this geriatric syndrome.
Recent findings
Anorexia of aging is extremely common, occurring in up to 30% of elderly individuals; however, this
diagnosis is frequently missed or erroneously attributed to a normal part of the aging process. With aging,
impairments in smell and taste can limit the desire to eat. Alterations in stress hormones and inflammatory
mediators can lead to excess catabolism, cachexia, and reduced appetite. In addition, mood disorders,
such as anxiety and depression, are powerful inhibitors of appetite. Anorexia of aging, with its negative
consequences on weight and muscle mass, is a risk factor for the development of frailty and is important
to screen for, as early intervention is key to reversing this debilitating condition.
Summary
Anorexia of aging is a complex geriatric syndrome and a direct risk factor for frailty and thus should not
be accepted as normal consequence of aging. Early diagnosis and formulating a plan for targeted
interventions is critical to prevent disability and preserve function in elderly patients.
Keywords
anorexia of aging, frailty, reduced appetite in the elderly

INTRODUCTION vulnerable elders. Anorexia of aging and subsequent

Anorexia of aging, first described in 44 B.C. by the
Roman philosopher Marcus Cicero, refers to the
reduction in appetite and food intake that is com-
monly seen with advancing age. In the modern
world, the concept was revived in 1988 by Morley
and Silver [1] and has since been a topic of much
research and debate. Considered a geriatric syn-
drome, anorexia of aging has a complex pathophysi-
ology, and multifaceted interventions are required
to prevent adverse health consequences. It can be a
direct risk factor for weight loss and the subsequent
development of sarcopenia. Frailty is a geriatric
syndrome characterized by an overall reduction in
physiologic reserve, impaired mobility, inactivity,
weakness, and increased vulnerability to environ-
mental and biological stressors [2]. Weight loss
is one of the core five components of the frailty
physical phenotype [3]. Frequently, the terms ‘ano-
rexia of aging’, ‘sarcopenia’, and ‘frailty’ are used
interchangeably in clinical practice, but each of
these is indeed a distinct entity and requires differ-
ent clinical approaches [4] (Fig. 1). Furthermore,
each of these alone and in combination can ulti-
mately cause loss of function and disability, along
with an overall decreased sense of well-being [5] in
frailty should not be accepted as a normal con-
sequence of aging but rather viewed as illnesses
amenable to treatment primarily with lifestyle
modifications and occasionally, pharmacological
therapy.
PREVALENCE
The prevalence of anorexia of aging is truly
unknown [6], but some studies suggest that it may
affect up to 20–30% of elderly individuals [7]. This
is, in part, due to the fact that aging is associated
with a physiological decrease in food intake, match-
ing the decrease in activity seen in most people.
In one study, total food intake was reduced in
older participants. It also demonstrated that eating
Division of Geriatric Medicine, Saint Louis University School of Medicine,
St. Louis, Missouri, USA
Correspondence to Angela M. Sanford, MD, Assistant Professor of
Internal Medicine-Geriatrics, Saint Louis University School of Medicine,
Division of Geriatric Medicine, 1402 South Grand Boulevard, M238, St.
Louis, MO 63104, USA. Tel: +1 314 977 8462; e-mail: lipkaa@slu.edu
Curr Opin Clin Nutr Metab Care 2017, 20:54–60
DOI:10.1097/MCO.0000000000000336

www.co-clinicalnutrition.com Volume 20  Number 1  January 2017

Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved.


KEY POINTS
 Anorexia of aging refers to a reduction of appetite and
food intake that is commonly seen with advancing age.
 Frailty is characterized by a reduction in physiologic
reserve, impaired mobility, inactivity, weakness, and
increased vulnerability to environmental and
biological stressors.
 Anorexia of aging is a direct precursor and risk factor
for frailty.
 Both anorexia of aging and frailty are treatable
geriatric syndromes, but treatment is often complex and
requires multifaceted interventions.
patterns were different in older persons in compari-
son with their younger counterparts. Specifically,
elderly individuals consumed less meat, fruits, and
vegetables, whereas consuming similar amounts of
dairy and grain products. This study also found that
anorexia of aging was more prevalent in women
and more common in institutional settings versus
community dwellings [7]. Despite its high preva-
lence, anorexia of aging is frequently not recognized
by physicians or is commonly accepted as a ‘normal’
part of aging and is thus often not diagnosed
or treated.
The prevalence of frailty is dependent on the
exact definition used and the criteria used for
measurement. One study found frailty to be
present in 12–28% of elders, with a higher preva-
lence in older women than men [8], whereas
another study, evaluating frailty in home health-
care recipients, found the prevalence to be 19–44%
[9]. One study found frailty to be positively
associated with the presence of depression, lower
socioeconomic status, lower education level, and
single relationship status [10]. Many older persons
with an acceptable nutritional status have been
shown to have poor protein intake which can lead
to sarcopenia and frailty [11]. Frailty is related to
poor nutritional quality [12,13]. Although the
true prevalence of frailty is difficult to ascertain,
its negative impact on health outcomes has been
globally demonstrated across studies [14], and
frailty is consistently linked to increased falls
[15], longer hospital stays [16], institutionalization
[17], and mortality [18].
Older persons with anorexia of aging are at
increased risk to develop severe anorexia, muscle
wasting, and frailty when they become ill [19]. The
mechanisms of anorexia in the anorexia–cachexia
syndrome overlap with those causing the physio-
logical anorexia of aging [20].
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Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved.
Anorexia of aging and its role for frailty Sanford
Anorexia of
aging
Weight
Frailty
loss
Sarcopenia
FIGURE 1. Relationship of anorexia of aging, weight loss,
sarcopenia, and frailty.
PATHOPHYSIOLOGY OF ANOREXIA OF
AGING
The pathophysiology of anorexia of aging is quite
complex because many factors – biological, social,
environmental, and psychological – contribute to
regulation of appetite and food intake (Fig. 2). In
many cases, it is the accumulation of deficiencies,
rather than just one deficit, that results in anorexia
of aging and its adverse consequences. Discussing
the complex neuroendocrine pathways and hor-
mones that are involved in the pathogenesis of
anorexia of aging are beyond the scope of this
article, but we will discuss some of the more basic
mechanisms in detail. These have recently been
reviewed in detail elsewhere [21].
Biological factors
There are numerous biological factors, some simple
and some more complex, which contribute to
anorexia of aging. In general, our sense of smell
and taste become impaired as we age, which can
affect our desire to eat. It has been shown that 50%
of those between the ages of 65 and 80 years and
75% of those greater than 80 years of age suffer
from decreased olfactory function [22]. Anosmia,
or reduced sense of smell, commonly occurs in this
age group because of changes in olfactory epithelial
cells, leading to altered nasal mucous production,
dysfunctional nasal engorgement, and an overall
reduction in the regeneration of olfactory receptors
[22]. Hypogeusia, or dampened sensation of taste,
tends to occur in older individuals because of the
loss in number and sensitivity of papillae on the
tongue. While often a physiologic process seen
with aging, numerous medications can cause accel-
eration in this process and further damage the
www.co-clinicalnutrition.com 55
Ageing: biology and nutrition
Demena/cognive
Delayed gastric impairment
emptying
Depression
Early saety
Polypharmacy
Diminished
socializaon
Inadequate
denon
Impairment of
smell
Limited access to
grocery store
FIGURE 2. Contributing factors to anorexia of aging.
senses [23]. For some elderly individuals, dental
problems, such as missing or broken teeth and
improperly fitting dentures, may significantly
impair their ability to chew and thus cause limita-
tion of dietary choices. If one is unable to chew his
or her favorite foods, it is reasonable to assume that
caloric intake may suffer. Atropinic drugs which
produce a dry mouth leading to decreased food
intake have been demonstrated to be a cause of
frailty [24].
Another prevalent biological mechanism alter-
ing food consumption in the elderly is elevated
proinflammatory cytokines. It has been hypothes-
ized that aging in itself is an inherent form of stress,
leading to increased cortisol and catecholamine
release, which in turn, result in up-regulation of
inflammatory cytokines, such as TNF-alpha and
interleukins [25]. These proinflammatory cytokines
have been associated with excess catabolism,
cachexia, and reduced food intake. In addition,
important mechanisms include alterations in the
production of appetite-regulating peptides and
hormones as well as abnormal physiologic responses
to these substances. Many of these hormones influ-
ence gastric emptying and satiety, or feeling of
satisfaction after food intake. When the satiation
cascade is impaired, and gastric emptying is delayed,
appetite is often diminished and meals are smaller
and less frequent. The neuroendocrine axis is
equally important in regulating appetite and con-
sists of numerous central and peripheral pathways.
56 www.co-clinicalnutrition.com
Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved.
Inability to Increased
prepare meals inflammatory
cytokines
Loss of Conspaon
Dysphagia taste
Restricve
diets
Reduced acvity
level
Reduced resng
metabolic rate
Acute illness
Chronic illness
Anorexia
Gastroesophageal reflux
of aging
Further discussion of these is beyond the scope of
&&
this article but is reviewed elsewhere [26 ,27].
Psychological, social, and environmental
factors
One of the most important conditions to diagnose
and treat when evaluating an individual with
suspected anorexia of aging is depression. Poor out-
comes from frailty are strongly associated with
depression [28]. Mood disorders such as anxiety
and depression are powerful inhibitors of appetite
in the elderly and are common reversible causes
of anorexia and weight loss. There are many causes
of depression in older individuals, including the
loss of spouses and other important loved ones, the
feelings of loneliness and isolation that often come
from living alone, the loss of a sense of purpose that
may stem from being retired from the workforce or no
longer being a primary caregiver to children or an
aging spouse, and the overall loss of independence.
Many elderly men have never been the primary meal
preparers, and the task of cooking and preparing
meals for oneself can be daunting enough that food
intake is impaired. Similarly, for elderly women, the
enjoyment of meal preparation may be diminished
now that they are no longer cooking for their families
or children. Eating in humans is often a ‘social’
behavior and is frequently tied to social events. Many
older adults feel socially isolated because they no
longer drive or are unable to travel easily outside of
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 Anorexia of aging and its role for frailty Sanford

their homes to see friends and family, which may Table 1. FRAIL scale
cause food intake to suffer. Additional factors to
consider that may contribute to anorexia of aging Yes No
are lack of financial resources to buy food, lack of Fatigue 1 point 0 points
transportation to the grocery store, decreased func-
‘Do you feel tired?’
tional ability to stand in the kitchen and prepare
Resistance 1 point 0 points
meals, and possible coexisting cognitive impairment,
‘Do you have
limiting one’s ability to ‘remember’ to eat. Many of
difficulty walking
the above are correctable or treatable once identified up one flight of
through obtaining a comprehensive history of social stairs?’
behavior and eating patterns. Ambulation 1 point 0 points
‘Do you have
difficulty walking
PATHOPHYSIOLOGY OF FRAILTY one block?’
The pathophysiology of frailty is equally as complex Illness 1 point 0 points
as the pathophysiology of anorexia of aging, and ‘Do you have five or
there is some overlap of underlying mechanisms more illnesses?’
between the two. There is debate as to whether Loss of weight 1 point 0 points
frailty is an actual phenotype or an overall state of ‘Have you lost more
being. Those who see frailty as a phenotype feel that than 5% body
weight in the past
frailty is the result of any of the following: history of 12 months?’
weight loss, decline in activity level, and/or objec-
tively measured slowing in gait speed or weakened 0–5 Points awarded with 0 ¼ best and 5 ¼ worst. Score of robust ¼ 0,
grip strength [2]. The underlying physiological prefrail ¼ 1–2, and frail ¼ 3–5. Data from [24].

framework responsible for the phenotype of frailty

is elevated inflammatory cytokines, reduced regen-
erative capacity, imbalanced hormones, additive
oxidative stress, and mitochondrial dysfunction,
leading to an overall dysregulation of the energy
cycle [2]. Those who believe that frailty is a state of
being argued that frailty results from accumulation
of health deficits as one ages and that there are
&&
different degrees of frailty [29 ]. Both trains of
thought encompass the idea that frailty is the result
of abnormalities in many systems or disease proc-
esses, rather than involvement of a single system or
single disease. Anorexia of aging, with its negative
consequences on weight and muscle mass, is a direct
risk factor for the development of frailty.
SCREENING
The goal of screening for both anorexia of aging and
frailty is to identify those who are at risk for weight
loss so that interventions can be put in place,
ideally, before the weight loss occurs. There are
numerous highly validated screening tools that
can be used. The Simplified Nutritional Assessment
Questionnaire consists of four short questions, thus
can be administered in under 1 min, and has been
validated to predict risk of more than 5% weight loss
in both community dwelling elders and nursing
home residents [30]. More recently, it has been
validated in other countries [31,32 ]. The Mini
&&
Nutritional Assessment (MNA) is another fairly
quick, validated tool that is useful in assessing
overall nutritional status in the geriatric population
[33]. Although the MNA has classically been used to
identify malnutrition, it also appears to be a strong
indicator of frailty [34,35]. There are also several
instruments that can be used to screen for frailty.
One of the simplest, most comprehensive scales is
the FRAIL scale, which is a five-item questionnaire
that evaluates for the core features of frailty – pres-
ence of fatigue, decreased resistance, difficulty with
ambulation, loss of weight, and presence of more
than five illnesses [36] (Table 1). When evaluating
for weight loss, one must also screen for depression,
as this is one of the most common reversible factors
leading to decreased appetite. Two tools that are
useful in screening for depression are the geriatric
depression scale (GDS) and the patient health ques-
tionnaire [37,38]. The GDS has five different ver-
sions (30, 15, 10, 8, and 4 item) and thus can be
shortened if there are time constraints.
The FRAIL-NH scale was created for nursing
home residents [39]. It stresses the importance of
food intake and weight loss in developing frailty in
this population. It has been validated as a useful
frailty tool in long term care [40,41]. Improving food
intake in long-term care remains a major component
of improving outcome in these frail individuals [42].
TREATMENT
Until recently, there has been a shortage of well
designed clinical trials to assess the short and

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Ageing: biology and nutrition
long-term efficacy of medical interventions for
frailty, and for its precursor, anorexia of aging
[43]. One reason for this is that there is not yet a
standardized definition of frailty. Another reason is
that frailty is such a multidimensional concept,
targeting one single area or domain may not yield
significant results. That being said, the intervention
that has been studied the most and that has yielded
quite positive results, is physical exercise [44–46]. It
is not clear at this time exactly what type of exercise
regimen is most beneficial, but meta-analyses
suggest that a multicomponent program including
cardio, balance, and strength training would be
most ideal [47]. By increasing overall strength, exer-
cise will improve the other core components of
frailty – gait speed, grip strength and ambulation.
It can also reduce the risk of weight loss by stimulat-
ing appetite and caloric intake and improve the state
of most chronic diseases.
Likewise, exercise is a key component in the
treatment of anorexia of aging because it is a multi-
faceted intervention addressing many of the factors
causing poor appetite and weight loss. For example,
exercise reduces depression [48], boosts ability
to perform independent activities of daily living
(i.e., cooking for oneself), improves constipation,
decreases proinflammatory cytokines/stress, incites
socialization if done outside of the home, increases
resting metabolic rate and in turn, sparks appetite
[49].
Along with initiating an exercise regimen in
those at risk for anorexia of aging and frailty, it is
equally important to optimize nutritional status.
Poor nutritional and protein intake as well as low
vitamin D, all of which are related to anorexia,
should be screened for in frail patients [50]. One
study found that a higher protein intake, specifi-
cally, greater than 1 g/kg body weight/day, is associ-
ated with a lower prevalence of frailty, whereas
increasing overall energy intake through means
other than protein did not reduce the prevalence
of frailty [51]. There are also several studies that
suggest the combination of exercise and optimizing
nutritional status is likely better than either
intervention alone [52,53]. Luger et al. [54] showed
that a volunteer program including exercise, nutri-
tion support and socialization reduced malnutrition
and frailty in older persons. Ng et al. [55] found
that various combinations of physical exercise,
behavioral therapy, and nutrition supplementation
improved frailty status of the individuals in their
6-month trial.
An important part of anorexia in the pathogen-
esis of frailty is the fact that this is often associated
with extremely poor protein intake [56,57]. As both
frailty and its major component sarcopenia are
58 www.co-clinicalnutrition.com
Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved.
strongly related to poor protein intake, reversal of
protein deficits and obtaining a protein intake of
at least 1 g/kg/day is important for reversal of these
conditions [58]. Leucine-enriched essential amino
acids and its metabolite, beta-hydroxy-betamethyl
butyrate both stimulate protein synthesis [59].
A recent multicenter trial has shown that protein
supplementation increased both muscle mass and
stair climb [60].
Of note, although there are several drugs on the
market that have been approved by the Food and
Drug Administration (FDA) as appetite stimulants,
their side-effects and lack of clinically meaningful
efficacy limit their use in many elderly patients. Two
of the most commonly prescribed appetite stimu-
lants, megestrol acetate and dronabinol, are actually
only approved by the FDA for cancer and AIDS-
related cachexia and thus must be used ‘off-label’
for anorexia of aging. With rare exceptions, the risks
of these medications outweigh the benefits in most
elderly patients with anorexia of aging and frailty.
Testosterone has been shown to improve a
6-min walk distance in older persons [61] and has
consistently been demonstrated to increase muscle
mass and strength in older persons with low testos-
terone [62]. Antibodies to myostatin have been
developed that show small effects on muscle mass
and strength in humans [63].
CONCLUSION
Not only are we striving to live longer in the current
era, more importantly, we are striving to live better
for longer. Prevention of disability and preservation
of functional independence should be one of the
&&
main goals of healthcare in older adults [26 ]. To
achieve this, predisability states must be recognized
and targeted interventions put in place before the
development of disability. On the continuous spec-
trum of robustness and disability, anorexia of aging
and frailty are intermediaries, and each stage in this
continuum is somewhat reversible or correctable. It
is important to keep in mind that both anorexia of
aging and frailty are potentially modifiable disease
processes and should be routinely diagnosed and
treated by clinicians. Furthermore, once recognized,
early intervention is key to successfully halting this
destructive pathway. A rapid geriatric assessment
that includes short screens for frailty, sarcopenia,
and anorexia is being piloted on a number of centers
around the world to see if early intervention for
these conditions will enhance clinical outcomes
in older persons [64]. Simple interventions such as
altering oral food as well as exploring the treatable
causes of anorexia and weight loss have a high
potential to reduce frailty [42,65].
Volume 20  Number 1  January 2017

Acknowledgements
I would like to thank Dominic E. Sanford, MD, MPHS for
his help with developing the figures.
Financial support and sponsorship
None.
Conflicts of interest
There are no conflicts of interest.
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Volume 20  Number 1  January 2017