Physiol Rev 86: 651– 667, 2006;
doi:10.1152/physrev.00019.2005.
Nutrition and Aging: Changes in the Regulation
of Energy Metabolism With Aging
SUSAN B. ROBERTS AND IRWIN ROSENBERG
The Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, Massachusetts
Downloaded from http://physrev.physiology.org/ by 10.220.33.3 on July 4, 2017
I. Introduction
II. Changes in the Regulation of Energy Intake
A. Comparisons of young and elderly adults
B. Reduced hunger and increased satiation as mediators of impaired defense
against energy imbalance
C. Glucose and insulin as potential mediators of impaired regulation of food intake
D. Other hormonal mediators of impaired regulation of food intake
E. Changes in taste and smell as potential contributors to impaired regulation of food intake
F. Reduced dietary variety as a mediator of impaired regulation of food intake
G. Medical and social factors
III. Changes in Energy Expenditure With Aging
A. Basal metabolic rate
B. The thermic effect of feeding
C. Total energy expenditure and physical activity level
D. Energy expenditure responsiveness to energy imbalance
IV. Changes in Fuel Utilization With Aging
V. Summary, Conclusions, and Future Directions
651
652
652
653
654
655
656
657
657
657
657
658
659
660
661
662
Roberts, Susan B., and Irwin Rosenberg. Nutrition and Aging: Changes in the Regulation of Energy Metabolism
With Aging. Physiol Rev 86: 651– 667, 2006; doi:10.1152/physrev.00019.2005.—Changes in energy regulation occur
during normal aging and contribute to the common phenomenon of weight and fat losses late in life. This review
synthesizes data on aging-related changes in energy intake and energy expenditure and on the regulation of energy
intake and expenditure. The ability of older adults to accurately regulate energy intake is impaired, with a number
of possible explanations including delayed rate of absorption of macronutrients secondary to reductions in taste and
smell acuity and numerous hormonal and metabolic mediators of energy regulation that change with aging. There
are also changes in patterns of dietary intake and a reduction in the variety of foods consumed in old age that are
thought to further reduce energy intake. Additionally, all components of energy expenditure decrease with aging, in
particular energy expenditure for physical activity and basal metabolic rate, and the ability of energy expenditure to
increase or decrease to attenuate energy imbalance during overeating or undereating also decreases. Combined,
these changes result in an increased susceptibility to energy imbalance (both positive and negative) in old age that
is associated with deteriorations in health. Practical interventions for prevention of weight and fat fluctuations in old
age are anticipated here based on emerging knowledge of the role of such factors as dietary variety, taste, and
palatability in late-life energy regulation.
I. INTRODUCTION
The human life cycle has undergone dramatic
changes in the last century. At the beginning of the 20th
century, average life expectancy at birth in the United
States for males and females combined was a mere 50
years. Now, 100 years later, average life expectancy is 77
years and is anticipated to increase to an average of 85
years by the year 2125. This change is due primarily to
www.prv.org
compression in morbidity rather than to an extension of
maximum life span. As a result of this, many more individuals are now living longer during the period when they
can be classified as “elderly,” and the percentage of the
United States population over the age of 65 years has
increased from 4% in 1900 to 13% currently (34).
In recognition of the changing world demographics,
studies of the effects of aging on physiology and metabolism are increasingly being scrutinized for their ability to
0031-9333/06 $18.00 Copyright © 2006 the American Physiological Society
651
652
SUSAN B. ROBERTS AND IRWIN ROSENBERG
II. CHANGES IN THE REGULATION
OF ENERGY INTAKE
A. Comparisons of Young and Elderly Adults
Several disease states common in old age, such as
cancer, are well known to be associated with body weight
and fat losses. However, there has been no general
consensus until recently over whether healthy aging is
also associated with weight loss mediated by a decreased ability to regulate energy intake (22, 24, 107,
108, 125, 132, 139).
The first study of this topic was by Roberts et al.
(132), who investigated whether older age is associated
with altered energy intake responses to imposed over-
feeding and underfeeding. Since day-to-day variability in
energy intake is typically 20 –25% (4) while day-to-day
variability in energy expenditure is typically only 10%
(53), there are necessarily substantial day-to-day fluctuations in energy balance. Overfeeding and underfeeding
protocols are usually thus an attempt to examine experimentally the effects of variability in energy intake and
energy balance within magnitudes that may occur during
usual life. In the studies of Roberts et al. (132), separate
overfeeding and underfeeding studies were conducted,
with young and elderly men enrolled in each protocol.
There were clear differences between age groups in body
weight change (and energy intake) following the intervention, as summarized in Figure 1. Whereas young men
responded to overfeeding by decreasing subsequent energy intake and to underfeeding by increasing subsequent
energy intake, elderly men had neither of these responses.
In consequence, young men tended to lose all the excess
weight they gained during overfeeding, and after underfeeding gained back more weight than they had lost during the experimental period, whereas elderly men lost
only 29% of the excess weight gained during overfeeding
and gained back only 64% of the weight lost during underfeeding.
Thus, in two separate protocols involving opposite,
experimentally imposed changes in energy balance, older
men had a substantial reduction in their ability to maintain a constant long-term weight and presumably energy
balance compared with young men. The fact that the
same result was obtained under opposite experimental
conditions (overfeeding and underfeeding) suggested a
basic difference between age groups rather than an ex-
FIG. 1. Body weight change in two groups of subjects during a 21-day period of underfeeding or overfeeding and subsequent ad libitum eating.
Values are means ⫾ SE for young and older men (black bars are young men, open bars are older men). Mean values were significantly different
between young and older men at the point of lowest/highest weight (P ⬍ 0.05). [From Roberts et al. (132).]
Physiol Rev • VOL
86 • APRIL 2006 •
www.prv.org
Downloaded from http://physrev.physiology.org/ by 10.220.33.3 on July 4, 2017
contribute to better approaches for improving the quality
of life in older individuals and preventing late-life disabilities. In this context, understanding changes in energy
regulation with aging is particularly important, because
prevention of weight loss and fat loss is an important
component of maintaining health in old age. The changing
demographics now also suggest that weight loss in older
persons may not necessarily be manifested by body mass
index in underweight ranges; indeed, in National Health
and Nutrition Survey (NHANES) II, involuntary weight
loss appeared disproportionately in older obese adults
and is associated with increased mortality (145).
This review synthesizes data and reviews changes
seen in energy regulation with aging and our emerging
understanding of underlying mechanisms.
AGING AND ENERGY REGULATION
B. Reduced Hunger and Increased Satiation
as Mediators of Impaired Defense
Against Energy Imbalance
The causes of apparent dysregulation of food intake
in old age are not well understood, in large part because
the mechanisms underlying successful energy regulation
at any age are not fully understood. In young adults, it is
generally accepted that multiple overlapping mechanisms
exist to regulate energy balance within fairly narrow limits, with hunger and satiety being monitored both peripherally and centrally by several systems. These mechanisms have not proven to be resistant to environmental
pressures to overeat, as seen in secular trends of weight
gain worldwide during the past 30 years (46). However,
Physiol Rev • VOL
there is general agreement that bodily mechanisms for
energy regulation do typically protect children and young
adults from weight loss if not weight gain. Thus there are
multiple candidates for age-related changes that could
contribute to the anorexia of aging, as outlined in several
recent reviews (8, 10, 62, 108, 111, 126, 134). It is important to recognize that redundancy in energy regulation
mechanisms is likely, because of the essentiality of maintaining energy balance within limits that do not prejudice
reproduction during young adult life and species survival
generally, and this implies that multiple pathways need to
fail in old age before a measurable impairment in energy
regulation is seen. Thus quite a large number of candidate
mechanisms may potentially be impaired in old age for
impaired regulation of energy intake to be seen, and work
is needed to identify which mechanisms are quantitatively
important. The strongest candidates based on current
knowledge are summarized below and are combined in a
suggested model in Figure 2.
Concerning evidence that the presumed intermediate
end points of energy deregulation, hunger and satiety (the
latter being defined as the sensation of fullness resulting
from eating that leads to cessation of eating), are altered
in old age, several studies have documented abnormally
low hunger following fasting or experimental induction of
negative energy balance in elderly subjects (22, 24, 58,
107, 139, 173, 194, 198). Moriguti et al. (107) reported
older subjects in an experimental underfeeding study experienced significantly less frequent symptoms of hunger
(assessed using visual analog scales) than young subjects,
despite the fact that the older subjects lost significantly
more weight and would therefore be expected to experience more frequent hunger. In addition, Clarkston et al.
(22) reported that carefully screened older persons
tended to be less hungry than younger persons after a
standardized overnight fast, and after a standard meal
they reported a greater degree of satiation than did
younger persons. Intraduodenal nutrient infusion has also
been reported to reduce hunger in young but not elderly
adults (24), while a low perception of hunger during daily
life assessed by the eating inventory questionnaire (173)
predicted a 0.5-kg weight loss per year in a group of
women with an average age of 61 at baseline (58). Sturm
and co-workers (175, 176) further suggested that both
decreased premeal hunger and increased postmeal satiation are independent contributors of impaired energy regulation in old age and that the increased satiation is
associated with increased antral area (and presumably
distension) after consumption of meals. This latter suggestion is also consistent with the animal literature suggesting that low energy intake leading to weight loss in
elderly rats is caused by consumption of smaller meals of
shorter duration, rather than normal-sized meals at reduced frequency (9). Combined, these results suggest that
a reduced perception of hunger and/or increased satiation
86 • APRIL 2006 •
www.prv.org
Downloaded from http://physrev.physiology.org/ by 10.220.33.3 on July 4, 2017
perimental artifact and implies that aging is indeed associated with an impaired ability to accurately regulate
energy balance through adjustments in energy intake.
However, an unresolved question raised by that study was
whether the weight changes persisted over an extended
period of time, because the follow-up period was relatively short (⬃7 wk). In a separate study by the same
group (107), body weight change following experimental
underfeeding was studied for a 6-mo period. As in the first
study, young normal-weight subjects regained essentially
all the weight lost during underfeeding, but elderly subjects only gained back 20% of the weight they lost on
average. On a shorter time scale, consistent results have
also been reported by two other groups. Rolls et al. (139)
gave yogurt preloads to young and older men and measured compensation for the additional energy at the subsequent meal. They observed that young men precisely
compensated for the preload with the result that net food
intake was relatively unaffected, whereas older men did
not. Morley (108) also gave preloads to young and older
subjects and found less complete compensation in the
older subjects than the young ones.
These four studies, together with several animal studies reporting impaired regulation of food intake in old age
(11, 27, 56, 65, 70, 76, 108, 187, 194, 196), suggest markedly
impaired regulation of energy intake in late life. Moreover,
when interpreting the combined results from these investigations, it is important to recognize that, as with most
studies of human aging physiology, the subjects were
healthy older men and women who would be predicted to
be less likely to exhibit age-related decrements in function than the more typical elderly individual with multiple
health problems. Thus, although the results observed here
should not be extrapolated beyond the types of diets and
experimental conditions used in the study, they may nevertheless underestimate the true extent of energy dysregulation in more typical elderly individuals with multiple chronic diseases.
653
654
SUSAN B. ROBERTS AND IRWIN ROSENBERG
precede and are contributing factors to weight loss in
old age.
C. Glucose and Insulin as Potential Mediators
of Impaired Regulation of Food Intake
Alterations in glucose homeostasis in old age may
contribute to altered hunger and satiety. Blood glucose
has long been postulated to be a trigger for hunger signals
in both rodents and humans (2, 10, 17, 19, 90, 98), and
recent studies in young adults and animal models linking
transient small decreases in blood glucose to initiation of
food consumption have provided tentative data in support
of this speculation (20, 170). Also consistent are the multiple studies of the effect of dietary glycemic index1 on
hunger and energy intake (reviewed in Ref. 127), suggesting that foods with a high glycemic index, such as white
bread, breakfast cereals, and other refined carbohydrates
(which typically have a glycemic index of 100 –120 when
white bread is used as the reference with a value set at
100 and which induce relative hypoglycemia 90 –120 min
after food consumption) promote a more rapid return of
hunger and an increase in subsequent energy intake.
1
Glycemic index is a property of food which is defined as the area
under the glucose curve after consumption of the food in an amount
containing 50 g carbohydrate, divided by the area under the plasma
glucose concentration curve versus time over 2 h after consumption of
white bread or glucose (these are two different standards) also containing 50 g carbohydrate.
Physiol Rev • VOL
Most young adults maintain circulating glucose
within the range of 80 –140 mg/dl throughout cycles of
feeding and fasting, through balanced alterations in secretions of insulin and counterregulatory hormones that
serve to facilitate uptake and synthesis and release of
glucose under different metabolic conditions. However,
when hypoglycemia occurs, it powerfully elicits sensations of hunger in young adults. In contrast, even healthy
older adults have a broader range over which circulating
glucose is maintained and in addition have attenuated
counterregulatory responses and delayed recovery from
hypoglycemia (85, 99, 100). Melanson et al. (95) recently
reported persistently elevated postprandial glucose and
insulin in the older women following consumption of
2,092- and 4,184-kJ test meals compared with younger
women. Provided that central mechanisms for converting
a signal of low blood glucose into a sensation of hunger
are intact in older individuals, as one study (16) but not
some others (85, 99, 100) indicated, the elevated postprandial blood glucose (mean values of ⬃120 mg/dl compared
with ⬃100 mg/dl in young adults) observed by Melanson
et al. (95) could potentially lead to an attenuated return of
hunger in the postprandial period. The elevated circulating insulin levels (⬃8% higher than in young adults) that
are typical of the reduced insulin sensitivity occurring in
old age and which accompanied high postprandial glucose levels in that study (95) may also contribute to a
delayed return of hunger, perhaps through a central satiety effect of high insulin levels (196) or by altering central
sensitivity to other components in the cascade of mech-
86 • APRIL 2006 •
www.prv.org
Downloaded from http://physrev.physiology.org/ by 10.220.33.3 on July 4, 2017
FIG. 2. Suggested integrated model
of metabolic impairments in the normal
cascade of mechanisms regulating energy
intake with aging. CCK, cholecystokinin;
NPY, neuropeptide Y; FFA, free fatty acids. [Adapted from Roberts and Hays
(134).]
AGING AND ENERGY REGULATION
D. Other Hormonal Mediators of Impaired
Regulation of Food Intake
Aging is associated with impairments in numerous
hormonal systems within the body (101, 143), which may
additionally influence energy regulation and are reviewed
Physiol Rev • VOL
in detail elsewhere [for example, Blanton et al. (8) and
Horwitz et al. (62)]. Although it is not possible to discern
which of the many impairments noted below are quantitatively significant in the dysregulation of energy balance
in old age, future studies in humans and animals may help
to dissect out the key systems and individual factors.
Glucagon is currently suggested to be one of the
signals of satiation (50, 168, 174), with its action mediated
at least in part through vagal afferent signals from the
liver and perhaps also by increasing blood glucose (which
is another postulated signal, see above). Melanson et al.
(95) reported that elderly women have significantly elevated levels of glucagon by up to 25% in response to
consumption of meals of 2,092 kJ (500 kcal) or greater,
identifying a potential role for glucagon in the apparently
enhanced satiation associated with old age.
There is also evidence of both altered synthesis
and/or secretion and impaired central responsiveness to
gut hormones in late life. For example, fasting levels of
the postulated satiety hormone CCK are typically five
times higher in elderly individuals than in young adults
(83, 87, 170, 175), rise more in response to an intraduodenal fat infusion than in young adults (83), but appear to
have a weaker effect in suppressing satiety than expected
in relation to circulating levels (84, 175). Concerning evidence for impaired detection of gut hormone signals, the
rise in CCK, glucagon-like peptide 1 (GLP-1), and polypeptide YY associated with intraduodenal lipid infusion were
significantly correlated with a decrease in hunger in
young but not older individuals in one study (84). Consistent data were also obtained in animal models, with administration of exogenous CCK, bombesin, and calcitonin
having a greater suppressing effect on food intake in
young compared with elderly mice (169). Strum et al.
(175) recently suggested that in fact higher CCK in late life
is unrelated to the anorexia of aging, based on the finding
that abnormal circulating levels exist in both underweight
elders (presumably exhibiting the anorexia of aging) and
well-nourished elders (presumably without an anorexia of
aging). However, if energy dysregulation in old age requires both underlying biological impairments and lifestyle factors that (see below) promote expression of the
biological impairments, well-nourished elders could exhibit the same biological factors while differing only in
more favorable life-style conditions. Further work is
needed to elucidate the role of different metabolic parameters including CCK in the anorexia of aging.
Leptin (57, 199) has also been proposed as a candidate hormone for the anorexia of aging, but emerging data
now suggest this is unlikely. In young adults, leptin is
secreted by fat cells and acts centrally to reduce feeding
and to increase energy expenditure through pathways
thought to involve inhibition of synthesis of NPY, which
itself stimulates feeding (see below) (8). There is a significant correlation between circulating leptin and body fat
86 • APRIL 2006 •
www.prv.org
Downloaded from http://physrev.physiology.org/ by 10.220.33.3 on July 4, 2017
anisms that regulate food intake such as cholecystokinin
(CCK) and neuropeptide Y (NPY) (123, 163). Consistent
with the suggestion of an important role for elevated
circulating insulin and glucose in the impaired regulation
of food intake in old age, Wolden-Hanson et al. (196)
reported a greater increase in food intake following fasting in older animals given troglitazone (an insulin sensitizer) compared with young animals.
Persistently elevated postprandial glucose and insulin levels may themselves potentially be explained by a
reduced rate of gastric emptying in old age, since delayed
gastric emptying will extend the time period over which
nutrients appear in the circulation due to extended digestion. Although this is not the only potential explanation
for high circulating glucose following meal consumption
in elderly individuals (for example, delayed uptake of
glucose by muscle and liver could also provide an explanation), most studies examining gastric emptying in relation to age have reported a decreased rate in the elderly
(22, 38, 104, 184, 190). Delayed gastric emptying in general
has been linked to reduced hunger and increased satiety
(2, 22, 61, 165, 166), and thus may potentially contribute to
increased satiety and satiation and/or decreased hunger
in elderly. Several models of energy regulation (43, 47, 90)
postulate a central role for substrate availability in energy
regulation, and recent work on blood glucose and hunger
has supported the concept of a role for low blood glucose
in initiation of hunger signals in young adults (20, 82, 98,
127). Delayed gastric emptying presumably extends the
period over which not only glucose but also other energy
substrates are absorbed. In addition to influencing hunger
and satiety through the time course of postprandial nutrient availability, alterations in gastric emptying in old age
would presumably also result in a prolonged period of
stomach distension, which could additionally prolong satiation directly through afferent vagal signals (105).
Concerning the underlying causes of delayed gastric
emptying in the elderly, several mechanisms have been
suggested including increased phasic pyloric pressure
waves in response to nutrients in the duodenum (24),
impaired autonomic nervous system function (which is
common in the elderly), and persistently elevated antral
distension (175, 176) as described above. Morley (108) has
also suggested that a reduction in nitric oxide production
by the stomach in elderly adults may increase satiation by
reducing relaxation of the fundus and accelerating movement of food to the antrum.
655
656
SUSAN B. ROBERTS AND IRWIN ROSENBERG
E. Changes in Taste and Smell as Potential
Contributors to Impaired Regulation
of Food Intake
There are well-documented age-associated declines
in taste and smell sensitivity (36, 42, 151–155, 191) that
may play a more important role in the energy dysregulation of old age than currently recognized. In particular,
most studies (36, 42, 151–156, 191) suggest that detection
and recognition thresholds for salt and other specific
tastes increase with age, in part because of the use of
medications that impact taste (see below) but also because of a loss of functional taste bud number and structure (1) and impaired olfaction.
Intact senses of taste and smell appear to be necessary for the cephalic phase of digestion, which includes
the initial increases in salivary, gastric, pancreatic, and
intestinal secretions that initiate digestion (148, 153). The
Physiol Rev • VOL
cephalic phase of postprandial metabolism is initiated by
olfactory, gustatory, and cognitive stimulation by food
and includes activation of both the sympathetic and parasympathetic nervous systems, which in turn initiate and
augment multiple digestion-related processes that serve
to prepare the body to absorb nutrients (15). Cognitive,
visual, and olfactory stimulation can elicit a release of
saliva that averages between one-fourth and two-thirds of
that noted following masticating, but not swallowing,
food. Because saliva contains digestive enzymes that initiate the breakdown of starch, the increased production
of saliva following consumption of most foods (21, 197)
may actually accelerate carbohydrate digestion and absorption. Tasteless stimuli have minimal effect on gastric
acid release and pancreatic secretions, whereas palatable
foods have long been known to result in marked stimulation of secretions that may promote digestion (64, 117).
Related to this observation, there is preliminary evidence suggesting that palatability may influence the rate
of nutrient absorption and/or initiate gluconeogenesis
(147, 172). Sawaya et al. (147) observed that consumption
of bland foods decreases the glycemic response to test
meals compared with palatable meals of identical macronutrient composition, which suggests there may be a
reduced rate of gastric emptying and hence slower digestion of bland foods. Consistent results were reported by
LeBlanc and Brondel (72), and although Warwick et al.
(189) reported no differential effect of palatable versus
bland liquids on circulating glucose, liquid test meals
were used in that study. Liquids appear to have very
different effects on satiety from solids (89), which may
possibly explain the different results obtained. Teff and
Engelman (179) also found no difference in postprandial
blood glucose responses to palatable versus unpalatable
test foods, but the foods used in that study were only
chewed and not swallowed, which would be predicted to
attenuate the cephalic response.
If the losses in taste and smell associated with aging
have an equivalent effect (i.e., making food seem more
bland, as commonly reported), the anticipated decrease
in gastric emptying and likely delayed absorption of nutrients could help explain the reported increase in satiation and decrease in hunger in old age. Consistent with
this suggestion, elderly individuals eat more of individual
foods if they are flavor-enhanced (157), and in another
study smell was significantly correlated with hunger and
appetite (31). It should be noted that, in this latter study,
there was no association between smell and reported
energy intake; however, documented inaccuracies in the
measurement of reported energy intake (160) make the
validity of such correlations uncertain. Additionally reported by Schiffman et al. (152), elderly individuals have
a reduced ability to identify individual foods in blinded
tests. If foods taste more similar, the pleasure of a diverse
diet will presumably be reduced, thus tending to decrease
86 • APRIL 2006 •
www.prv.org
Downloaded from http://physrev.physiology.org/ by 10.220.33.3 on July 4, 2017
in young adults (23, 103, 136), but in elderly adults circulating leptin may be lower than expected for body fat
levels (8, 136). Furthermore (8, 88, 103, 136, 171, 195),
central leptin administration has relatively little effect on
food intake and thermogenesis in old, obese rats compared with substantial effects in young, lean ones (for
example, 42% reduction in food intake following central
leptin administration) (150) due to decreased leptin responsiveness in old age (149, 150, 167).
The fact that a variety of peripheral satiety signals,
including CCK, leptin, blood glucose, and the sympathetic
nervous system (70), and perhaps ghrelin (52) all appear
to be imperfectly detected in old age may be related to
impairments in one or more central mechanisms responsible for coordination of energy regulation signals. One
important potential candidate is NPY, one of the most
abundant peptides in the brain that is an integrator of
metabolic endocrine and behavioral systems (73, 74) and
acts through various hypothalamic nuclei to stimulate
feeding behavior and affect release of hormones that
modulate energy metabolism such as insulin (73, 74). The
finding of high levels of NPY in both plasma and cerebrospinal fluid of elderly anorectics provides some circumstantial evidence that NPY expression does not relate to
the anorexia of aging, since high NPY is predicted to
increase feeding in the young (87). However, the fastinginduced increases in both food intake and NPY gene
expression normally seen in young rats are consistently
attenuated in aging rats (55, 56, 76, 194), indicating that
responsiveness to NPY is impaired in old age. Consistent
with this suggestion, the feeding and drinking responses
to NPY injection in the paraventricular hypothalamic nucleus are markedly attenuated in aged rats (7, 118), with
only one-quarter to one-third of the response seen in
younger animals (7).
AGING AND ENERGY REGULATION
dietary variety in the absence of environmental and social
factors working in the opposite direction.
F. Reduced Dietary Variety as a Mediator
of Impaired Regulation of Food Intake
Physiol Rev • VOL
G. Medical and Social Factors
Many social and medical changes associated with
aging have been suggested to cause weight loss, such as
poverty, bereavement, social isolation, poor dentition,
chronic disease, and the use of multiple prescription medications (36, 54, 108 –111, 157). In addition, depression has
been suggested as an important cause of weight loss
among the elderly, a finding that has been confirmed in an
analysis of cohort data (35). However, it is interesting to
note that the study of DiPietro et al. (35) showed that
depression was associated with weight loss only in individuals aged 55 years or older and was actually associated
with weight gain in younger adults. One potential explanation for this finding (132) is that psychosocial factors
are potential catalysts for weight loss only when there is
an underlying impairment in the regulation of food intake
that allows impediments to eating to be expressed.
Concerning social isolation, de Castro and de Castro
(30) reported that less energy is eaten at meals taken
alone compared with meals eaten in company, with the
difference in energy intake between the two situations
being a substantial 30%. Although such data are generally
used to suggest that social eating is disadvantageous because it promotes overeating and obesity, the opposite
(namely, that eating alone leads to undereating and
weight loss) may be an equally valid interpretation. This is
especially true when it is considered that humans are a
gregarious animal species and naturally eat in social
groups (102). This is directly relevant to the issue of low
energy intake in the older population, because bereavement and functional disabilities can limit social contact
(86). Thus an increased frequency of eating alone may be
one of the factors contributing to low energy intake in
older adults. Furthermore, there is a positive association
between the frequency of eating restaurant food and body
fatness (91) and for reasons of social isolation and functional disabilities, older adults may eat out less frequently.
In support of this suggestion, in the recently reported
NHANES 1999 –2000 survey, adults younger than 45 years
of age reported meals out approximately twice as often as
those over the age of 65 years (66). The combination of
these different observations and findings suggests a potentially important role for reductions in social meals and
eating out in the low energy intake and body weight loss
of older adults, which is independent of any biological
impairments associated with aging.
III. CHANGES IN ENERGY EXPENDITURE
WITH AGING
A. Basal Metabolic Rate
Basal metabolic rate (BMR) is the energy expenditure of an individual after a 12- to 14-h overnight fast
86 • APRIL 2006 •
www.prv.org
Downloaded from http://physrev.physiology.org/ by 10.220.33.3 on July 4, 2017
Studies in laboratory rats, cats, and hamsters have
shown that energy intake is greater when a variety of
foods are provided compared with when only a single
food is provided (92, 93). Numerous single-meal studies in
humans also show this phenomenon (93, 141). While two
longer-term studies have shown that laboratory rats have
greater body fat and body fat gain when fed a variety of
foods compared with when only a single food is fed (81,
142), long-term studies in humans have been lacking until
recently. McCrory et al. (92) recently reported on the
long-term association between dietary variety and body
fatness in healthy adult men and women (92). In multiple
regression analyses controlled for age and sex, dietary
variety from a combined group of sweets, snacks, condiments, entrees, and carbohydrates was positively associated with body fatness, and in the same model dietary
variety from vegetables was negatively associated with
body fatness. In other words, individuals who consumed
a wide variety of higher energy foods coupled with a low
variety of vegetables were relatively fatter.
Self-reported records of dietary intake indicate that
dietary variety is reduced in old age (17, 39), and a recent
study also demonstrated particularly low dietary variety
among elderly adults with low body mass index (BMI)
(133). The reasons why dietary variety decreases in old
age and is particularly low in elders suffering from low
BMI are not fully understood but may potentially provide
an additional explanation for weight loss in old age. Concerning potential mechanisms, a study by Rolls and
McDermott (140) observed that older adults have reduced
“sensory specific satiety,” a term used to describe the
phenomenon of declining pleasantness of food as it is
consumed. The adolescent and young adult subjects of
Rolls and McDermott (140) responded in the expected
manner to a yogurt preload (i.e., decreased desire to eat
yogurt but not other offered foods), but older subjects did
not respond and in fact reported an equivalent desire to
eat yogurt and other test foods after the preload. Although
necessarily short-term and requiring confirmation in a
larger study, these data suggest that older adults lack
normal patterns of sensory specific satiety that encourage
wide dietary variety. The underlying reason for decreased
sensory specific satiety in old age may potentially be
traced back to the declines in taste and smell sensitivity
associated with aging documented above (36, 42, 151–156,
191), with their predicted impact on the extent of digestion and availability of incoming substrates into the circulation.
657
658
SUSAN B. ROBERTS AND IRWIN ROSENBERG
Physiol Rev • VOL
the forearm assessed by 31P-magnetic resonance spectroscopy, and Bosy-Westphal et al. (13) found no effect of
age on BMR when organ sizes within the free-fat mass
(assessed by magnetic resonance imaging) were taken
into account (different organs are known to have tissuespecific rates of energy expenditure). These reports, suggesting no effect of age on BMR beyond that due to the
loss of different body tissues is taken into account, would
appear to conflict with the further finding of Willis et al.
(193) that there is a significant age-associated decline in
cerebral glucose metabolism (indicating energy expenditure since glucose is the primary metabolic fuel of the
brain). However, Willis et al. (193) also quantified the
change in cerebral glucose metabolism with age, and the
estimated 5 g/day decrease in glucose use between 20 and
70 years for an adult with normal brain size would result
in an estimated decrease in BMR of only 125 kJ/day,
which is ⬍2% BMR for most adults and would not be
detected significantly except in extremely large studies.
Taken together, these observations indicate that BMR is
indeed lower in the elderly compared with young adults
even after taking body composition changes associated
with aging into account, but the difference is so small
(⬍2% based on changes in brain glucose metabolism) that
it can be considered insignificant.
B. The Thermic Effect of Feeding
The thermic effect of feeding, previously know as
specific dynamic action, is the increase in energy expenditure above basal that is associated with consuming,
digesting, and assimilating food. Some of the increase in
energy expenditure can be directly attributed to the metabolic costs of digestion, resynthesis of macronutrient
polymers, and related processes (termed “obligatory thermogenesis”), while the other component of the increase
appears to be due to concomitant activation of the sympathetic nervous system (termed “facultative thermogenesis”) (28).
The thermic effect of feeding is equivalent to 8 –15%
of ingested metabolizable energy. Some studies report a
decrease in the thermic effect of feeding in old age (51,
106, 161, 164, 180, 185), while other studies report no
change (27, 49, 96, 121, 182, 188). To avoid the potential
concern that meal size might influence differences in TEF
between young and older individuals, Melanson et al. (96)
measured the thermic effect of feeding at three levels of
energy intake. There was no significant difference in the
thermic effect of feeding between the age groups, and
mean postprandial values for energy expenditure above
initial fasting values were actually slightly higher in the
older group than the young group. Although no conclusive
explanation can currently be given for the different results between some of the studies, a suggested explana-
86 • APRIL 2006 •
www.prv.org
Downloaded from http://physrev.physiology.org/ by 10.220.33.3 on July 4, 2017
during a period of mental and physical rest in a thermoneutral environment and reflects energy use of the body
for such basic functions as maintenance of electrochemical gradients, transporting of molecules around the body,
and biosynthetic processes. Frequently, a “resting energy
expenditure” is measured in preference to a BMR. Resting
energy expenditure is quantitatively similar to the BMR,
but it is not subject to all the exacting requirements of a
BMR. In this review, measurements of resting energy
expenditure are taken to be equivalent to BMR.
Typically, BMR is the largest component of energy
expenditure and comprises 50 –70% of total expenditure
in most adults. A decline in BMR with aging is well
recognized (68, 119) and is implicit in standard equations
for predicting BMR in healthy men and women of different ages (40). A longitudinal study by Keys et al. (68)
documented a decline in BMR with age of 1–2% per decade; based on this assessment, a reduction in BMR of
⬃400 kJ/day can be predicted between 20 and 70 years
of age.
The question of whether the decline in BMR with
aging can be accounted for by concomitant alterations in
body composition, or whether there is also a decline in
BMR per unit of tissue, has been studied by several research groups. Many (48, 69, 116, 120, 128, 188) though
not all (26, 144, 183) cross-sectional studies reported that
BMR is lower in old age even after adjustment for lower
fat-free mass in older individuals, with adjusted BMR
values being ⬃5% lower for elderly adults than for young
adults. However, loss of fat-free mass is not the only body
composition change that occurs during the adult human
life cycle, and in particular, there is usually a substantial
increase in fat mass from young adulthood to middle age
that often quantitatively exceeds the concomitant loss of
fat-free mass (resulting in net weight gain). Two investigations also analyzed changes in BMR with aging in relation to individual variability in both fat-free mass and fat
mass (27, 186). In both of these studies, there was a
significantly lower BMR in elderly adults compared with
young ones. Because adipose tissue is metabolically active, albeit less metabolically active than muscle and
other components of fat-free mass (40), failure to account
for the increase in fat mass through middle age in analyses of BMR could theoretically underestimate BMR adjusted for fat-free mass and help explain the conflicting
results of the earlier studies.
More recently, three additional studies have further
examined BMR in relation to compartmentalized body
composition. Roubenoff et al. (144) examined BMR in
relation to total body potassium (an indicator of metabolically active tissue independent of such compartments as
extracellular water) and found no effect of age on the
relationship between total body potassium and BMR.
Consistent with this suggestion, Kutsuzawa et al. (71)
found no effect of age on muscle energy metabolism of
AGING AND ENERGY REGULATION
C. Total Energy Expenditure and Physical
Activity Level
The third major component of energy expenditure is
the energy expenditure for physical activity and arousal
(these individual components are usually grouped together due to the difficulty of separating them experimentally). Energy expenditure for physical activity and
arousal, together with the BMR and the thermic effect of
feeding, comprise an individual’s total energy expenditure, which is equivalent to dietary energy requirements
during weight maintenance. In theory, energy expenditure
for physical activity and arousal, and hence total energy
expenditure, can be determined by recording the amounts
of time devoted to different activities and the energy costs
of those activities (measured in a laboratory by respiratory gas exchange) and summing the individual components in what has been called the “factorial” method.
However, in practice it is difficult to avoid underestimation of energy expenditure by this method because it is
impossible to record every type of activity, and there are
nonaccountable activities such as fidgeting that tend to
get under-recorded (37, 135).
To avoid the pitfalls of the factorial method, substantial effort has been directed towards developing the doubly labeled water method as an alternative, longer term,
and more accurate technique for measurement of total
energy expenditure. This method was originally developed for use in small animals (77, 78), based on the
principle that if two isotopes of water (H218O and 2H2O)
are administered and their disappearance rates from a
body fluid such as urine monitored, the disappearance
rate of 2H2O reflects water flux and the disappearance
rate of H218O reflects water flux plus carbon dioxide
production rate (79). The difference between the two
disappearance rates can therefore be used to calculate
carbon dioxide production rate over a period of 1–3 wk,
from which total energy expenditure can be calculated if
information is available on respiratory quotient (177).
Physiol Rev • VOL
Validation studies of the doubly labeled water method
have been conducted in human infants and adults of
different ages using respiratory gas exchange or dietary
energy intake as the reference method (129, 159). All
these studies showed a close agreement between total
energy expenditure determined by doubly labeled water
and total energy expenditure determined by a reference
method, with a coefficient of variation for the new
method of 2– 6%. In consequence, the doubly labeled water method is now widely recognized as an accurate and
precise method for assessment of total energy expenditure in human subjects. Delayed isotopic equilibration is
recognized in elderly subjects, presumably due to the
incomplete bladder emptying that frequently occurs in old
age (6, 114, 158), but this effect has been demonstrated
only for short equilibration periods after dosing (such as
4 h); in practice, this limitation can be eliminated by
employing longer equilibration periods as recommended
by Blanc et al. (6). Because the doubly labeled water
method calculates the rate of carbon dioxide production,
rather than the rate of energy expenditure, and because
the heat equivalent of carbon dioxide varies with the
substrates being oxidized (129, 159), it is necessary to
have an estimate of the respiratory quotient (RQ) of the
subject during the measurement period. Usually, RQ is
estimated from information on the subjects’ dietary intake, either their reported macronutrient intakes or normative data from population surveys, and errors from
necessary assumptions and errors in dietary records are
recognized to be small and usually ⬍2% (177).
A critical mass of doubly labeled water data has
accumulated over the past 15 years, making it possible to
evaluate typical changes in total energy expenditure and
energy expenditure for physical activity (calculated as the
difference between total energy expenditure and BMR
plus the thermic effect of feeding, or indicated by a physical activity level calculated as the ratio of total energy
expenditure to BMR). Several studies have reported lower
total energy expenditure in elderly adults compared with
young adults (116, 122, 138, 148), and the summary of data
from different adult age-groups shown in Figure 3 illustrates a progressive substantial decline in total energy
expenditure (and hence physical activity level) with age
(5). Additional studies have also investigated differences
in 24-h sedentary energy expenditure when adults are
confined to a whole body calorimeter. In these studies,
sedentary energy expenditure is lower in elderly adults
than in young adults when activity in the chamber is
flexible (186), but in whole body calorimeter protocols
that standardize 24-h activity, there has been no difference in 24-h energy expenditure between age groups
(186). Taken together, these data demonstrate declines in
both planned exercise and spontaneous physical activity
in healthy old age.
86 • APRIL 2006 •
www.prv.org
Downloaded from http://physrev.physiology.org/ by 10.220.33.3 on July 4, 2017
tion (96) is that the thermic effect of feeding does not
decline with aging per se, but that some studies may have
confounded age with factors that decrease thermic effect
of feeding independent of aging, such as obesity and/or
digestive problems that limit nutrient absorption. Alternatively, one recent study documented decreased ␤-adrenergically stimulated thermogenesis in aging, seen as an
18% greater infusion of isoprenaline needed to increase
metabolic rate by 15% (67); the same group further reported diminished fat oxidation in response to isoprenaline (3). It is therefore possible that there is a small
decrease in the sympathetic nervous system component
of TEF with age but that quantitatively it is hard to detect
and has given rise to inconsistent results between studies.
659
660
SUSAN B. ROBERTS AND IRWIN ROSENBERG
small since any increase in energy expenditure associated
with training seems to be offset by decreased voluntary
energy expenditure at other times of the day (94, 192).
However small the effects on energy balance, additional
effects of exercise include positive effects on cardiovascular and bone health and prevention of falls and frailty.
D. Energy Expenditure Responsiveness
to Energy Imbalance
FIG.
The causes of declining total energy expenditure and
physical activity with age are not well understood. The
declines with age are reported to parallel an increase in
body fat mass, suggesting that changes in body composition may be important (130). Regression analyses predicting energy expenditure from body fat and fat-free mass in
individuals of different ages show that there is a positive
association between fat-free mass and energy expenditure but a negative association of fat mass with energy
expenditure (130). Thus it is reasonable to speculate that
the increase in body fat mass may help promote a decrease in energy expenditure for physical activity. In
NHANES III, in those over 70 years, increased BMI or
body fat was associated with limitations in functional
living activities such as carrying groceries, suggesting that
increasing body fat may influence energy expenditure
through impairment of daily activities (29). However,
Westerterp and Meijer and co-workers (94, 192) have
pointed out that the decline in physical activity energy
expenditure with age is most strongly predicted by age
itself and not by body composition, indicating an effect of
aging on expenditure independent of the quantity of lean
tissue and fat mass. It is also noteworthy that maximal
oxygen consumption is recognized to decline progressively with age, and very active individuals have declines
of ⬃50% between 20 and 80 years that are of similar
magnitude (albeit higher absolute values) to those experienced by sedentary individuals (33). These observations
suggest that some parallel changes in fitness, energy expenditure for physical activity, and body composition
with age are probably an inevitable consequence of the
aging process, probably due to underlying hormonal and
biochemical changes in skeletal muscle and the cardiovascular system rather than a cumulative consequence of
long-term inactivity. Further studies are needed to determine the extent to which energy expenditure for physical
activity can be maintained in old age in the general population, with the expectation based on current research
that potential specific effects on energy balance may be
Physiol Rev • VOL
The concept that energy expenditure plays an important role in the regulation of energy balance has been the
subject of numerous investigations since the beginning of
the 20th century (113), and it is now widely recognized
that energy expenditure increases or decreases only to a
limited extent to match energy intake to minimize
changes in energy balance resulting from overeating or
undereating (14, 59, 137).
Several studies published over the last decade have
suggested there may be important changes in energy expenditure responsiveness to changes in energy balance
with aging. Roberts and colleagues (107, 131, 146) conducted a series of overfeeding and underfeeding studies
to examine the magnitude of changes in total energy
expenditure and components of energy expenditure to
energy imbalance in young (age 20 –30 years) and elderly
(age 60 – 80 years) men. In a combined analysis of the first
overfeeding and underfeeding studies, a significantly attenuated resting energy expenditure response to changes
in energy balance was observed in the elderly men (Fig.
4). Thus, during positive energy balance, the increase in
FIG. 4. Relationship between energy deficit during underfeeding or
energy surplus during overfeeding and the change in resting energy
expenditure (REE) in young (closed circles) and older (open circles)
men. There was a significant age by change in energy intake interaction
(P ⬍ 0.05). The overall relationship for REE vs. change in energy intake
taking age group into account was also significant (R2 ⫺0.548, P ⬍
0.001). [Adapted from Salzman and Roberts (146).]
86 • APRIL 2006 •
www.prv.org
Downloaded from http://physrev.physiology.org/ by 10.220.33.3 on July 4, 2017
3. Total energy expenditure at different ages [males are solid
lines (⫾SD); females are dotted lines (⫾SD)]. The graph was prepared
with data from Black et al. (5).
AGING AND ENERGY REGULATION
IV. CHANGES IN FUEL UTILIZATION
WITH AGING
The ability of the body to oxidize dietary fat must be
a critical determinant of the success or failure of body
energy regulation, because exogenous fat that is not oxidized must be stored (43, 44). Thus, if fat oxidation can
adapt on a meal-to-meal or even week-to-week basis to
match the fat content of the diet, there will be no net fat
deposition or loss over time, and body adipose stores will
remain constant. However, body fat stores will increase if
fat oxidation is less than fat intake, and conversely, body
fat stores will decrease if fat oxidation is greater than fat
intake. The potential role of reduced fat oxidation in the
development of obesity in adults of all ages is seen in the
Physiol Rev • VOL
data from epidemiological studies that link consumption
of a high-fat diet to increased body fat (80) and in dietary
intervention studies that have showed higher energy intakes on high-fat diets than on low-fat diets matched for
palatability (80). More direct evidence is also seen in the
prospective studies that have demonstrated a significant
association between low fat oxidation, relative to intake,
and subsequent weight gain (200), although it is important
to note both that positive energy balance is essential for
net fat accumulation and that measurements of substrate
oxidation have a strong potential to be confounded by
uncontrolled dietary intake in the days before scientific
study.
Nevertheless, observations to date raise the question
of whether there might be age-associated alterations in fat
oxidation in the postprandial state that could help explain
age-associated changes in body fatness. In a longitudinal
24-h whole body calorimeter study, Rising et al. (124)
reported a mean 0.019 RQ increase over time in seven
Pima Indian subjects (indicating ⬃5% greater carbohydrate oxidation and 5% less fat oxidation), and consistent
results were more recently reported in a larger population
by Levadoux et al. (75). Melanson et al. (96) used postprandial measurements of oxygen consumption and carbon dioxide production to observe that, following meals
simulating the size of a snack or a small meal (1,046 and
2,092 kJ), older women had rates of fat oxidation comparable to those in young women (Fig. 5). However, the
same elderly women had significantly lower fat oxidation
following consumption of a moderately large meal (4,184
kJ). In regression analyses, maximal oxygen consumption, lean body mass, and circulating triglycerides explained individual differences in fat oxidation. However,
the number of subjects was rather small for this type of
analysis, and there were several similar models with comparable statistical significance, so the separation of age
from body composition and fitness was not possible.
These statistical findings are consistent with known influences on fat oxidation. For example, skeletal muscle mass
is known to be the primary site for fat oxidation, and
vigorous activity influences insulin sensitivity and hence
the extent to which fat is used as a fuel source instead of
carbohydrate (60).
Concerning fat oxidation in the fasting state, there
are reports of both increased and decreased fasting fat
oxidation in elderly individuals (12, 18). In addition,
Melanson et al. (97) observed no significant effects of age
per se on fasting fat oxidation measured over 10 h, but
there was a significant negative effect of body fat in the
best-fitting multiple regression model, which was probably due to the fact that the fatter subjects were in the
older group. These latter observations appear consistent
with the data of Calles-Escandon et al. (18) and lend
weight to the suggestion that aging may also be associated
with no increase in fat oxidation, and perhaps even a
86 • APRIL 2006 •
www.prv.org
Downloaded from http://physrev.physiology.org/ by 10.220.33.3 on July 4, 2017
resting energy expenditure was lower in elderly men than
young men relative to the level of energy imbalance.
Similarly, the decrease in resting energy expenditure with
negative energy balance was reduced in the elderly subjects. These changes can be predicted to result in greater
fluctuations in body weight and fat mass with overeating
and undereating in the elderly, due to reduced compensation from adaptive changes in energy expenditure. The
differences between the age groups were statistically explained by differences in muscle mass between the
groups, suggesting that 1) muscle is an important site of
adaptive thermogenesis in humans and 2) the declines in
muscle mass with age explain the reduced capacity for
changes in energy expenditure with negative energy balance. However, when the results of these studies were
separated into those obtained during overfeeding and
underfeeding, the age-group difference in change in resting energy expenditure was only significant in the overfeeding group. Thus the question of whether alterations in
energy expenditure responsiveness to changes in energy
balance are general or specific to negative energy balance
was unresolved.
To further examine this issue, the same group conducted a second, longer study to examine changes in the
capacity for reducing energy expenditure with negative
energy balance in young and elderly subjects. The results
of this second study were consistent with the combined
overfeeding/underfeeding analysis, showing an attenuated reduction in BMR during negative energy balance in
the elderly subjects compared with young subjects (27).
One theoretical expectation from these findings is that
elderly people should lose more weight for the same
decrement in energy intake. Consistent with this prediction, the second, longer underfeeding study in the series
documented greater weight loss during underfeeding in
elderly subjects than in young subjects despite the fact
that compliance with the study diet appeared to be no
different between the age groups.
661
662
SUSAN B. ROBERTS AND IRWIN ROSENBERG
decrease in fat oxidation after taking fat mass into account (which is positively correlated with fasting fat oxidation in younger subjects; see Ref. 162).
The fact that the apparent impairments in fat oxidation in old age are associated with reduced muscle mass
and fitness suggest that alterations in fuel availability with
age may underlie differences in fat oxidation, and therefore that exercise may help reverse or attenuate the ageassociated effects through alterations in insulin sensitivity. Consistent with this view, several previous studies,
Physiol Rev • VOL
V. SUMMARY, CONCLUSIONS,
AND FUTURE DIRECTIONS
Several lines of evidence demonstrate that dysregulation of energy intake occurs in old age even in apparently healthy individuals and increase the risk of energy
imbalance. There is also emerging data suggesting equivalent dysregulation of body energy expenditure and substrate oxidation in old age. The extent to which body
weight and fat increases or decreases in response to
age-related energy dysregulation will depend on the prevailing environmental circumstances and health of the
86 • APRIL 2006 •
www.prv.org
Downloaded from http://physrev.physiology.org/ by 10.220.33.3 on July 4, 2017
FIG. 5. Individual values for fat oxidation (corrected for postprandial energy expenditure) in relation to meal size and study duration in 16
young and older women. There was a significant age group by meal size
interaction (P ⬍ 0.02), and the older women had significantly lower
values for fat oxidation after consumption of the 4,148-kJ meal than did
the young women (P ⬍ 0.02). [From Melanson et al. (97).]
including one in elderly subjects, have reported increased
fasting fat oxidation with improved fitness, resulting from
increased muscle mass and increased activity of fat oxidative enzymes in muscle (60, 63, 181). Additional evidence comes from another study documenting impaired
fat oxidation in association with persistently high levels of
circulating glucose for several hours in the postmeal period after consumption of a moderate-large meal size (95).
The young women in that study responded to increasing
meal size with appropriately increased circulating insulin
and minimal changes in circulating glucagon, with the
result that circulating levels of glucose increased only
slightly with increasing meal size and showed the expected pattern of a small initial increase followed by a
rapid return to baseline. Appropriate patterns of insulin,
glucagon, and glucose were also seen in the older women
during the fasting experiment and after consumption of
the 1,046 kJ meal. In contrast, consumption of the
2,092-kJ meal, and to an even greater extent the 4,184-kJ
meal, caused a substantial prolonged increase in circulating levels of both insulin and glucagon (but not free fatty
acids) in the older group. The trend toward elevation in
glucagon with meal consumption is noteworthy because
it is in direct contradiction to the expected meal-induced
suppression of glucagon secretion in individuals without
non-insulin-dependent diabetes (25) and may well be a
contributor to the persistent postmeal elevation in circulating glucose. The net effect of these changes, coupled
with the expected underlying modest degree of insulin
resistance in older individuals (41), was a substantial
increase in the peak circulating glucose during the postmeal period and a persistent elevation of circulating glucose throughout the 5-h postprandial study period. Thus,
although classified as normally glucose tolerant in an oral
glucose tolerance test performed during the screening
examination, these older women did in fact exhibit abnormal glucose profiles when challenged with mixed
meals of 2,092 kJ or greater. Since fat oxidation is suppressed by high levels of circulating glucose (45), these
high levels of glucose help explain why fat oxidation was
suppressed.
AGING AND ENERGY REGULATION
individual. Since body weight change is associated with
such undesirable consequences as micronutrient deficiencies, frailty, increased hospital admission, an increased
risk of disability from falls, delayed recovery from injury,
and premature death (32, 112, 115, 178), further research
is clearly needed to identify the specific underlying causes
of aging-associated energy dysregulation. Current research also points to the potential for manipulation of
dietary factors such as variety, taste, and meal size for
preventing weight loss or weight gain through compensatory changes in energy intake.
ACKNOWLEDGMENTS
REFERENCES
1. Arey LB, Tremaine MJ, and Monzingo FL. The numerical and
topographical relations of taste buds to human circumvallate papillae throughout the life span. Anat Rec 64: 9 –25, 1936.
2. Bergmann JF, Chassany O, Petit A, Triki R, Caulin C, and
Segrestaa JM. Correlation between echographic gastric emptying
and appetite: influence of psyllium. Gut 33: 1042–1043, 1992.
3. Blaak EE, van Baak MA, and Saris WH. Beta-adrenergically
stimulated fat oxidation is diminished in middle-aged compared to
young subjects. J Clin Endocrinol Metab 84: 3764 –3769, 1999.
4. Black AE and Cole TJ. Within- and between-subject variation in
energy expenditure measured by the doubly-labelled water technique: implications for validating reported dietary energy intake.
Eur J Clin Nutr 54: 386 –394, 2000.
5. Black AE, Coward WA, Cole TJ, and Prentice AM. Human
energy expenditure in affluent societies: an analysis of 574 doublylabelled water measurements. Eur J Clin Nutr 50: 72–92, 1996.
6. Blanc S, Colligan AS, Trabulsi J, Harris T, Everhart JE,
Bauer D, and Schoeller DA. Influence of delayed isotopic equilibration in urine on the accuracy of the 2H218O method in the
elderly. J Appl Physiol 92: 1036 –1044, 2002.
7. Blanton CA, Horwitz BA, Blevins JE, Hamilton JS, Hernandez EJ, and McDonald RB. Reduced feeding response to neuropeptide Y in senescent Fischer 344 rats. Am J Physiol Regul
Integr Comp Physiol 280: R1052–R1060, 2001.
8. Blanton CA, Horwitz BA, and McDonald RB. Neurochemical
alterations during age-related anorexia. Proc Soc Exp Biol Med 221:
153–165, 1999.
9. Blanton CA, Horwitz BA, Murtagh-Mark C, Gietzen DW,
Griffey SM, and McDonald RB. Meal patterns associated with the
age-related decline in food intake in the Fischer 344 rat. Am J
Physiol Regul Integr Comp Physiol 275: R1494 –R1502, 1998.
10. Blundell JE. Understanding anorexia in the elderly: formulating
biopsychological research strategies. Neurobiol Aging 9: 18 –20,
1988.
11. Boghossian S, Veyrat-Durebex C, and Alliot J. Age-related
changes in adaptive macronutrient intake in swimming male and
female Lou rats. Physiol Behav 69: 231–238, 2000.
Physiol Rev • VOL
12. Bonadonna RC, Groop LC, Simonson DC, and DeFronzo RA.
Free fatty acid and glucose metabolism in human aging: evidence
for operation of the Randle cycle. Am J Physiol Endocrinol Metab
266: E501–E509, 1994.
13. Bosy-Westphal A, Eichhorn C, Kutzner D, Illner K, Heller M,
and Muller M. The age-related decline in resting energy expenditure in humans is due to the loss of fat-free mass and to alterations
in its metabolically active components. J Nutr 133: 2356 –2362,
2003.
14. Bouchard C, Tremblay A, Despres JP, Nadeau A, Lupien PJ,
Theriault G, Dussault J, Moorjani S, Pinault S, and Fournier
G. The response to long-term overfeeding in identical twins. N Engl
J Med 322: 1477–1482, 1990.
15. Brand JG, Cagan RH, and Naim M. Chemical senses in the
release of gastric and pancreatic secretions. Annu Rev Nutr 2:
249 –276, 1982.
16. Brierley EJ, Broughton DL, James OFW, and Alberti KGMM.
Reduced awareness of hypoglycaemia in the elderly despite an
intact counter-regulatory response. Q J Med 88: 439 – 445, 1995.
17. Brown EL. Factors influencing food choices and intake. Geriatrics
31: 89 –92, 1976.
18. Calles-Escandon J, Arciero PJ, Gardner AW, Bauman C, and
Poehlman ET. Basal fat oxidation decreases with aging in women.
J Appl Physiol 78: 266 –271, 1995.
19. Campfield LA and Smith FJ. Blood glucose dynamics and control of meal initiation: a pattern detection and recognition theory.
Physiol Rev 83: 25–58, 2003.
20. Campfield LA, Smith FJ, Rosenbaum M, and Hirsch J. Human
eating: evidence for a physiological basis using a modified paradigm. Neurosci Behav Rev 20: 133–137, 1996.
21. Christensen CM and Navazexh M. Anticipatory salivary flow to
the sight of different foods. Appetite 5: 307–315, 1984.
22. Clarkson WK, Pantano MM, Morley JE, Horowitz M, Littlefield JM, and Burton FR. Evidence for the anorexia of aging:
gastrointestinal transit and hunger in healthy elderly vs. young
adults. Am J Physiol Regul Integr Comp Physiol 272: R243–R248,
1997.
23. Considine RV, Sinha MK, Heiman ML, Kriauciunas A, Stephens TW, Nyce MR, Ohannesian JP, Marco CC, McKee LJ,
Bauer TL, and Caro JF. Serum immunoreactive-leptin concentrations in normal-weight and obese humans. N Engl J Med 334:
292–295, 1996.
24. Cook CG, Andrews JM, Jones KL, Wittert GA, Chapman IM,
Morley JE, and Horowitz M. Effects of small intestinal nutrient
infusion on appetite and pyloric motility are modified by age. Am J
Physiol Regul Integr Comp Physiol 273: R755–R761, 1997.
25. Cryer PE. Glucose homeostasis and hypoglycemia. In: William’s
Textbook of Endocrinology (8th ed.), edited by Wilson JD and
Foster DW. Philadelphia, PA: Saunders, 1992, p. 1223–1253.
26. Cunningham JJ. A reanalysis of the factors influencing basal
metabolic rate in normal adults. Am J Clin Nutr 33: 2372–2374,
1980.
27. Das SK, Moriguti JC, McCrory MA, Saltzman E, Mosunic C,
Greenberg AS, and Roberts SB. An underfeeding study in
healthy men and women provides further evidence of impaired
regulation of energy expenditure in old age. J Nutr 131: 1833–1838,
2001.
28. Das SK and Roberts SB. Energy metabolism. In: Present Knowledge in Nutrition (8th ed.), edited by Bowman BA and Russell RB.
Washington, DC: ISLI, 2001.
29. Davison KK, Ford ES, Cogswell ME, and Dietz WH. Percentage
of body fat and body mass index are associated with mobility
limitations in people aged 70 and older from NHANES III. J Am
Geriatr Soc 50: 1802–1809, 2002.
30. De Castro JM and de Castro ES. Spontaneous meal patterns of
humans: influence of the presence of other people. Am J Clin Nutr
50: 237–247, 1989.
31. De Jong N, Mulder I, de Graaf C, and van Staveren WA.
Impaired sensory functioning in elders: the relation with its potential determinants and nutritional intake. J Gerontol A Biol Sci Med
Sci 54: B324 –B331, 1999.
86 • APRIL 2006 •
www.prv.org
Downloaded from http://physrev.physiology.org/ by 10.220.33.3 on July 4, 2017
We thank all the members of the Energy Metabolism Laboratory at the Jean Mayer USDA Human Nutrition Research
Center on Aging at Tufts University for their invaluable contributions to the studies described in this review, in particular,
Paul Fuss, Gaston Bathalon, Nicholas Hays, Kathleen Melanson,
Megan McCrory, and Edward Saltzman. We also gratefully acknowledge the enduring inspiration of our late colleague and
friend Vernon R. Young.
Address for reprint requests and other correspondence:
S. B. Roberts, Energy Metabolism Laboratory, USDA Human Nutrition Research Center on Aging at Tufts University, 711 Washington St., Boston, MA 02111 (e-mail: [email protected]).
663
664
SUSAN B. ROBERTS AND IRWIN ROSENBERG
Physiol Rev • VOL
57. Halaas JL, Gajiwala KD, Maffei M, Cohen SL, Chait BT, Rabinowitz D, Lallone RL, Burley SK, and Friedman JM. Weightreducing effects of the plasma protein encoded by the obese gene.
Science 269: 543–546, 1995.
58. Hays NP, Bathalon GP, Roubenoff R, McCrory MA, and Roberts SB. Eating behavior and weight change in healthy postmenopausal women: results of a 4-year longitudinal study. J Gerontol. In
press.
59. Heyman M, Young VR, Fuss P, Tsay R, Joseph L, and Roberts
SB. Underfeeding and body weight regulation in normal weight
young men. Am J Physiol Regul Integr Comp Physiol 263: R250 –
R257, 1992.
60. Holloszy JO. Utilization of fatty acids during exercise. In: Biochemistry of Exercise. VIII. International Series on Sports Sciences. Champaign, IL: Human Kinetic Books, 1990, p. 319 –327.
61. Horowitz M, Jones K, Edelbroek MA, Smout AJ, and Read
NW. The effect of posture on gastric emptying and intragastric
distribution of oil and aqueous meal components and appetite.
Gastroenterology 105: 382–390, 1993.
62. Horwitz BA, Blanton CA, and McDonald RB. Physiologic determinants of the anorexia of aging: insights from animal studies.
Annu Rev Nutr 22: 417– 438, 2002.
63. Hurley BF, Nemeth PM, and Martin WH. Muscle triglyceride
utilization during exercise: effect of training. J Appl Physiol 60:
562–567, 1986.
64. Janowitz HD, Hollander F, and Orringer D. A quantitive study
of the gastric secretory response to sham-feeding in a human
subject. Am J Gastroenterol 16: 104 –116, 1950.
65. Kaneda T, Makino S, Nishiyama M, Asaba K, and Hashimoto
K. Differential neuropeptide responses to starvation with ageing.
J Neuroendocrinol 13: 1066 –1075, 2001.
66. Kant AK and Graubard BI. Eating out in America, 1987–2000:
trends and nutritional correlates. Prev Med 38: 243–249, 2004.
67. Kerckhoffs DA, Blaak EE, Van Baak MA, and Saris WH. Effect
of aging on beta-adrenergically mediated thermogenesis in men.
Am J Physiol Endocrinol Metab 274: E1075–E1079, 1998.
68. Keys A, Taylor HL, and Grande F. Basal metabolism and age of
adult man. Metabolism 22: 579 –587, 1973.
69. Klausen B, Toubro S, and Astrup A. Age and sex effects on
energy expenditure. Am J Clin Nutr 65: 895–907, 1997.
70. Kumar MV, Moore RL, and Scarpace PJ. B3-adrenergic regulation of leptin, food intake, and adiposity is impaired with age.
Pflügers Arch 438: 681– 688, 1999.
71. Kutsuzawa T, Shioya S, Kurita D, Haida M, and Yamabayashi
H. Effects of age on muscle energy metabolism and oxygenation in
the forearm muscles. Med Sci Sports Exercise 33: 901–906, 2001.
72. LeBlanc J and Brondel L. Role of palatability on meal induced
thermogenesis in human subjects. Am J Physiol Endocrinol Metab
248: E333–E336, 1985.
73. Leibowitz SF. Brain neurotransmitters and eating behavior in the
elderly. Neurobiol Aging 9: 20 –22, 1988.
74. Leibowitz SF. Brain neurotransmitters and hormones in relation
to eating behavior and its disorders. In: Obesity, edited by Bjorntorp P and Brodoff BN. Philadelphia, PA: Lippincott, 1992, p. 184 –
205.
75. Levadoux E, Morio B, Montaurier C, Puissant V, Boirie Y,
Fellmann N, Picard B, Rousset P, Beaufrere B, and Ritz P.
Reduced whole-body fat oxidation in women and in the elderly. Int
J Obes Relat Metab Disord 25: 39 – 44, 2001.
76. Li H, Matheny M, Tumer N, and Scarpace PJ. Aging and fasting
regulation of leptin and hypothalamic neuropeptide Y gene expression. Am J Physiol Endocrinol Metab 275: E405–E411, 1998.
77. Lifson N. Theory of use of the turnover rates of body water for
measuring energy and material balance. J Theoret Biol 12: 46 –74,
1966.
78. Lifson N, Gordon GB, and McClintock R. Measurement of total
carbon dioxide production by means of D218O. J Appl Physiol 7:
704 –710, 1955.
79. Lifson N, Gordon GB, Visscher MB, and Nier AO. The fate of
utilized molecular oxygen and the source of oxygen of respiratory
carbon dioxide, studied with the aid of heavy oxygen. J Biol Chem
180: 803– 811, 1949.
86 • APRIL 2006 •
www.prv.org
Downloaded from http://physrev.physiology.org/ by 10.220.33.3 on July 4, 2017
32. Delmi M, Rapin CH, Bengoa JM, Delmas PD, Vasey H, and
Bonjour JP. Dietary supplementation in elderly patients with fractured neck of the femur. Lancet 335: 1013–1016, 1990.
33. Department of Health and Human Services. Physical Activity
and Health: A Report of the Surgeon General Atlanta, Georgia:
USDHSS, Centers for Disease Control and Prevention. Washington, DC: DHHS, 1996, p. 1–77.
34. Department of Health and Human Services. Department of
Health and Human Services Website, Administration of Aging Division (www.DHHSA.aoa.dhhs.gov).
35. DiPietro L, Anda RF, Williamson DF, and Stunkard AJ. Depressive symptoms and weight change in a national cohort of
adults. Int J Obesity 16: 745–753, 1992.
36. Doty RL, Shaman P, Applebaum SL, Giberson R, Sikorski L,
and Rosenberg L. Smell identification ability: changes with age.
Science 226: 1441–1443, 1984.
37. Durnin JVGA. Low energy expenditures in free-living populations.
Eur J Clin Nutr 44: 95–102, 1990.
38. Evans MA, Triggs EJ, Cheung M, Broe GA, and Creasey H.
Gastric emptying rate in the elderly: implications for drug therapy.
J Am Geriatr Soc 29: 201–205, 1981.
39. Fanelli MT and Stevenhager KJ. Characterizing consumption
patterns by food frequency methods: core foods and variety of
foods in diets of older Americans. J Am Diet Assoc 85: 1570 –1576,
1985.
40. FAO, WHO, and UNU. Energy and protein requirements. Report of
a joint FAO/WHO/UNU expert consultation. Technical Report Series 724. Geneva: World Health Organization, 1985.
41. Ferrannini E, Vichi S, Beck-Nielsen H, Laakso M, Paolisso G,
and Smith U. Insulin action and age. Diabetes 45: 947–953, 1996.
42. Finkelstein JA and Schiffman SS. Workshop on taste and smell
in the elderly: an overview. Physiol Behav 66: 173–176, 1999.
43. Flatt JP. Dietary fat, carbohydrate balance, and weight maintenance: effects of exercise. Am J Clin Nutr 45: 296 –306, 1987.
44. Flatt JP. Importance of nutrient balance in body weight regulation. Diabetes Met Rev 4: 571–581, 1988.
45. Flatt JP. McCollum Award Lecture, 1995: Diet, lifestyle, and
weight maintenance. Am J Clin Nutr 62: 820 – 836, 1995.
46. Flegal KM, Carroll MD, Kuczmarski RJ, and Johnson CL.
Overweight and obesity in the United States: prevalence and
trends, 1960 –1994. Int J Obesity 22: 39 – 47, 1998.
47. Friedman MI. Control of energy intake by energy metabolism.
Am J Clin Nutr 62: 1096S–1100S, 1995.
48. Fukagawa NK, Bandini LG, and Young JB. Effect of age on body
composition and resting metabolic rate. Am J Physiol Endocrinol
Metab 259: E233–E238, 1990.
49. Fukagawa NR, Bandini LG, Lim PH, Roingeard F, Lee MA, and
Young JB. Protein-induced changes in energy expenditure in
young and old individuals. Am J Physiol Endocrinol Metab 260:
E345–E352, 1991.
50. Geary N. Pancreatic glucagon signals postprandial satiety. Neurosci Biobehav Rev 14: 323–338, 1990.
51. Golay A, Schutz Y, and Meyer HU. Glucose induced thermogenesis in nondiabetic and diabetic obese subjects. Diabetes 31: 1023–
1028, 1982.
52. Golden JK, Das SK, McCrory MA, Roberts SB, and Saltzman
E. Fasting ghrelin change after weight loss is attenuated in the
elderly. North American Association for the Study of Obesity 2005
Annual meeting, Vancouver Canada.
53. Goran MI, Beer WH, Wolfe RR, Poehlman ET, and Young VR.
Variation in total energy expenditure in young healthy free-living
men. Metabolism 42: 487– 496, 1993.
54. Gorbien MJ. Anorexia of aging: a simple approach to management. Cleve Clin J Med 61: 253, 1994.
55. Gruenewald DA, Marck BT, and Matsumoto AM. Fasting-induced increases in food intake and neuropeptide Y gene expression
are attenuated in aging male Brown Norway rats. Endocrinology
137: 4460 – 4467, 1996.
56. Gruenewald DA, Naai MA, Marck BT, and Matsumoto AM.
Age-related decrease in neuropeptide-Y gene expression in the
arcuate nucleus of the male rat brain is independent of testicular
feedback. Endocrinology 134: 2383–2389, 1994.
AGING AND ENERGY REGULATION
Physiol Rev • VOL
101. Minaker KL, Meneilly GS, and Rowe JW. Endocrine systems. In:
Handbook of the Biology of Aging, edited by Finch C and Hayflick
L. New York: Van Nostrand Reinhold, 1984, p. 433– 456.
102. Mintz SW and Du Bois CM. The anthropology of food and eating.
Annu Rev Anthropol 31: 99 –119, 2002.
103. Moller N, O’Brien P, and Nair KS. Disruption of the relationship
between fat content and leptin levels with aging in humans. J Clin
Endocrinol 83: 931–934, 1998.
104. Moore JG, Tweedy C, Christian PE, and Datz FL. Effect of age
on gastric emptying of liquid-solid meals in man. Dig Dis Sci 28:
340 –344, 1983.
105. Moran TH, Ladenheim EE, and Schwartz GJ. Within-meal gut
feedback signaling. Int J Obes Relat Metab Disord 25: S39 –S41,
2001.
106. Morgan JB and York DA. Thermic effect of feeding in relation to
energy balance in elderly men. Ann Nutr Metab 27: 71–77, 1983.
107. Moriguti JC, Das SK, Saltzman E, Corrales A, McCrory MA,
Greenberg AS, and Roberts SB. Effects of a 6-week hypocaloric
diet on changes in body composition, hunger and subsequent
weight regain in healthy young and older adults. J Gerontol 55A:
8580 – 8587, 2000.
108. Morley JE. Anorexia of aging: physiologic and pathologic. Am J
Clin Nutr 66: 760 –773, 1997.
109. Morley JE. The role of nutrition in the prevention of age-associated diseases. In: Geriatric Nutrition: A Comprehensive Review,
edited by Morley JE, Glick Z, and Rubenstein LZ. New York: Raven,
1990, p. 89 –103.
110. Morley JE, Kumar VB, Muttammal M, Farr S, Morley PM, and
Flood JF. Inhibition of feeding by L-NAME: effects of aging. Eur
J Pharmacol 311: 15–29, 1996.
111. Morley JE and Silver AJ. Anorexia in the elderly. Neurobiol
Aging 9: 9 –16, 1988.
112. Mowe M, Bohmer T, and Kindt E. Reduced nutritional status in
an elderly population (⬎70 y) is probable before disease and
possibly contributes to the development of disease. Am J Clin Nutr
59: 317–324, 1994.
113. Neumann RO. Experimentalle bejtrage zur lehre von dem taglichen nahoungsbedarf des menschen unter besonder berucik sichtigung def notwendiger eiweissmenge. Arch Hyg Bakteriol 45:
1– 87, 1902.
114. Ouslander JG, Hepps K, Raz S, and Su HL. Genitourinary dysfunction in a geriatric outpatient population. J Am Geriatr Soc 34:
507–514, 1986.
115. Pamuk ER, Williamson DF, Madans J, Serdula MK, Kleinman
JC, and Byers T. Weight loss and mortality in a national cohort of
adults, 1971–1987. Am J EpidemIOL 136: 686 – 697, 1992.
116. Pannemans DLE and Westerterp KR. Energy expenditure, physical activity and basal metabolic rate of elderly subjects. Br J Nutr
73: 571–581, 1995.
117. Pavlov I. The Work of the Digestive Glands. London: Griffin, 1902,
p. 20 – 44.
118. Pich EM, Messori B, Zoli M, Ferraguti F, Marrama P, Biagini
G, Fuxe K, and Agnati LF. Feeding and drinking responses to
neuropeptide Y injections in the paraventricular hypothalamic nucleus of aged rats. Brain Res 575: 265–271, 1992.
119. Poehlman ET. Energy expenditure and requirements in aging
humans. J Nutr 122: 2057–2065, 1992.
120. Poehlman ET, Melby CL, and Bradylak SF. Relation of age and
physical exercise status on metabolic rate in younger and older
healthy men. J Gerontol 46: B54 –B58, 1991.
121. Poehlman ET, Viers HF, and Detzer M. Influence of physical
activity and dietary restraint on resting energy expenditure in
young nonobese females. Can J Physiol Pharmacol 69: 320 –326,
1991.
122. Reilly JJ, Lord A, Bunker VW, Prentice AM, Coward WA,
Thomas AJ, and Briggs RS. Energy balance in healthy elderly
women. Br J Nutr 69: 21–27, 1993.
123. Riedy CA, Chavez M, Figlewicz DP, and Woods SC. Central
insulin enhances sensitivity to cholecystokinin. Physiol Behav 58:
755–760, 1995.
124. Rising R, Tataranni P, Snitker S, and Ravussin E. Decreased
ratio of fat to carbohydrate oxidation with increasing age in pima
indians. J Am Coll Nutr 15: 309 –312, 1996.
86 • APRIL 2006 •
www.prv.org
Downloaded from http://physrev.physiology.org/ by 10.220.33.3 on July 4, 2017
80. Lissner L, Levitsky DA, Strupp BJ, Kalkwarf HJ, and Roe DA.
Dietary fat and the regulation of energy intake in human subjects.
Am J Clin Nutr 46: 886 – 892, 1987.
81. Louis-Sylvestre J, Giachetti I, and LeMagnen J. Sensory versus
dietary factors in cafeteria-induced overweight. Physiol Behav 32:
901–905, 1984.
82. Ludwig DS, Majzoub JA, Al-Zahrani A, Dallal GE, Blanco I,
and Roberts SB. High glycemic index foods, overeating, and
obesity. Pediatrics 103: E261–E266, 1999.
83. MacIntosh CG, Andrews JM, Jones KL, Wishart JM, Morris H,
Jansen JB, Morley JE, Horowitz M, and Chapman IM. Effects
of age on concentrations of plasma cholecystokinin, glucagon-like
peptide 1, and peptide YY and their relation to appetite and pyloric
motility. Am J Clin Nutr 69: 999 –1006, 1999.
84. MacIntosh CG, Morley JE, Wishart J, Morris H, Jansen JB,
Horowitz M, and Chapman IM. Effect of exogenous cholecystokinin (CCK)-8 on food intake and plasma CCK, leptin, and insulin
concentrations in older and young adults: evidence for increased
CCD activity as a cause of the anorexia of aging. J Clin Endocrinol
Metab 86: 5830 –5837, 2001.
85. Marker JC, Cryer PE, and Clutter WE. Attenuated glucose
recovery from hypoglycemia. Diabetes 41: 671– 678, 1992.
86. Markson EW. Functional, social, and psychological disability as
causes of loss of weight and independence in older communityliving people. Clin Geriatr Med 13: 639 – 652, 1997.
87. Martinez M, Hernanz A, Gomex-Cerezo J, Pena JM, Vazquez
JJ, and Arnalich F. Alterations in plasma and cerebrospinal fluid
levels of neuropeptides in idiopathic senile anorexia. Regul Pept 49:
109 –117, 1993.
88. Matsumoto AM, Marck BT, Gruenewald DA, Wolden-Hanson
T, and Naai MA. Aging and the neuroendocrine regulation of
reproduction and body weight. Exp Gerontol 35: 1251–1265, 2000.
89. Mattes RD. Dietary compensation by humans for supplemental
energy provided as ethanol or carbohydrate in fluids. Physiol Behav 59: 179 –187, 1996.
90. Mayer J. Glucostatic mechanisms of the regulation of food intake.
N Engl J Med 249: 13–16, 1953.
91. McCrory MA, Fuss PJ, Hays NP, Vinken AG, Greenberg AS,
and Roberts SB. Overeating in America: association between
restaurant food consumption and body fatness in healthy adult
men and women ages 19 to 80. Obesity Res 7: 564 –571, 1999.
92. McCrory MA, Fuss PJ, McCallum JE, Yao M, Vinken AG, Hays
NP, and Roberts SB. Dietary variety within food groups: association with energy intake and body fatness in adult men and women.
Am J Clin Nutr 69: 440 – 447, 1999.
93. McCrory MA, Fuss PJ, Saltzman E, and Roberts SB. Dietary
determinants of energy intake and weight regulation in healthy
adults. J Nutr 130: 276S–279S, 2000.
94. Meijer EP, Westerterp KR, and Verstappen FT. Effect of exercise training on physical activity and substrate utilization in the
elderly. Int J Sports Med 21: 499 –504, 2000.
95. Melanson KJ, Greenberg AS, Ludwig DS, Saltzman E, Dallal
GE, and Roberts SB. Blood glucose and hormonal responses to
small and large meals in healthy young and older women. J Gerontol 53: B299 –B305, 1998.
96. Melanson KJ, Saltzman E, Russell R, and Roberts SB. The
effects of age on postprandial thermogenesis at four graded energetic challenges: findings in young and older women. J Gerontol
53B: 409 – 414, 1998.
97. Melanson KJ, Saltzman E, Russell RR, and Roberts SB. Fat
oxidation in response to four graded energy challenges in younger
and older women. Am J Clin Nutr 66: 860 – 866, 1997.
98. Melanson KJ, Westerterp-Plantenga MS, Camfield LA, and
Saris WHM. Appetite and blood glucose profiles in humans after
glycogen-depleting exercise. J Appl Physiol 87: 947–954, 1999.
99. Meneilly GS, Cheung E, and Tuokko H. Altered responses to
hypoglycemia of healthy elderly people. Clin Endocrinol Metab 78:
1341–1348, 1994.
100. Meneilly GS, Cheung E, and Tuokko H. Counterregulatory hormone responses to hypoglycemia in the elderly patient with diabetes. Diabetes 43: 403– 410, 1994.
665
666
SUSAN B. ROBERTS AND IRWIN ROSENBERG
Physiol Rev • VOL
149.
150.
151.
152.
153.
154.
155.
156.
157.
158.
159.
160.
161.
162.
163.
164.
165.
166.
167.
168.
169.
170.
171.
172.
mined by using the doubly labeled water method. Am J Clin Nutr
62: 338 –344, 1995.
Scarpace PJ, Matheny M, Moore RL, and Tumer N. Impaired
leptin responsiveness in aged rats. Diabetes 49: 431– 435, 2000.
Scarpace PJ, Matheny M, Zhang Y, Tumer N, Frase CD, Shek
EW, Hong B, Prima V, and Zolotukhin S. Central leptin gene
delivery evokes persistent leptin signal transduction in young and
aged-obese rats but physiological responses become attenuated
over time in aged-obese rats. Neuropharmacology 42: 548 –561,
2002.
Schiffman SS. Changes in taste and smell: drug interactions and
food preferences. Nutr Rev 52: S11–S14, 1994.
Schiffman SS. Food recognition by the elderly. J Gerontol 32:
586 –592, 1977.
Schiffman SS. Taste and smell losses in normal aging and disease.
JAMA 278: 1357–1362, 1997.
Schiffman SS, Moss J, and Erickson RP. Thresholds of food
odors in the elderly. Exp Aging Res 2: 389 –398, 1976.
Schiffman SS and Pasternak M. Decreased discrimination of
food odors in the elderly. J Gerontol 34: 73–79, 1979.
Schiffman SS and Warwick ZS. Effect of flavor enhancement of
foods for the elderly on nutritional status: food intake, biochemical
indices, and anthropometric measures. Physiol Behav 53: 395– 402,
1993.
Schiffman SS and Warwick ZS. Use of flavor-amplified foods to
improve nutritional status in elderly patients. In: Nutrition and the
Chemical Senses in Aging: Recent Advances and Current Research Needs, edited by Murphy C, Cain WS, and Hegstead DM.
New York: NY Acad. Sci., 1989, p. 267–276.
Schnelle JF, Traughber B, Sowell VA, Newman DR, Petrilli
CO, and Ory M. Prompted voiding treatment of urinary incontinence in nursing home patients. A behavior management approach
for nursing home staff. J Am Geriatr Soc 37: 1051–1057, 1989.
Schoeller DA. Measurement of energy expenditure in free-living
humans by using doubly labeled water. J Nutr 118: 1278 –1289,
1988.
Schoeller DA, Bandini LG, and Dietz WH. Inaccuracies in selfreported intake identified by comparison with the doubly labelled
water method. Can J Physiol Pharmacol 68: 941–949, 1990.
Schutz Y, Bessard T, and Jequier E. Diet-induced thermogenesis
measured over a whole day in obese and nonobese women. Am J
Clin Nutr 40: 542–552, 1984.
Schutz Y, Flatt JP, and Jequier E. Failure of dietary fat intake to
promote fat oxidation: a factor favoring the development of obesity. Am J Clin Nutr 50: 307–314, 1989.
Schwartz MW, Figlewicz DP, Woods SC, Porte DJ, and Baskin
DG. Insulin, neuropeptide Y, and food intake. Ann NY Acad Sci
692: 60 –71, 1993.
Schwartz RS, Jaegar LF, and Veith RC. The thermic effect of
feeding in older men: the importance of the sympathetic nervous
system. Metabolism 39: 733–737, 1990.
Sepple CP and Read NW. Gastrointestinal correlates of the development of hunger in man. Appetite 13: 183–191, 1989.
Shafer RB, Levine AS, Marlette JM, and Morley JE. Effects of
xylitol on gastric emtying and food intake. Am J Clin Nutr 45:
744 –747, 1987.
Shek EW and Scarpace PJ. Resistance to the anorexic and thermogenic effects of centrally administrated leptin in obese aged
rats. Regul Pept 92: 65–71, 2000.
Shulman JL, Carleton JL, Whitney G, and Whitehorn JC.
Effect of glucagon on food intake and body weight in man. J Appl
Physiol 11: 419 – 421, 1957.
Silver AJ and Flood JF. Effect of gastrointestinal peptides on
ingestion in old and young mice. Peptides 9: 221–225, 1988.
Smith GP and Gibbs J. The satiating effects of cholecystokinin.
Curr Concepts Nutr 16: 35– 40, 1988.
Soares MJ, Piers LS, O’Dea K, and Collier GR. Plasma leptin
concentrations, basal metabolic rates and respiratory quotients in
young and older adults. Int J Obes Relat Metab Disorders 24:
1592–1599, 2000.
Strubbe JH. Parasympathetic involvement in rapid meal-associated conditioned insulin secretion in the rat. Am J Physiol Regul
Integr Comp Physiol 263: R615–R618, 1992.
86 • APRIL 2006 •
www.prv.org
Downloaded from http://physrev.physiology.org/ by 10.220.33.3 on July 4, 2017
125. Roberts SB. Effects of aging on energy requirements and the
control of food intake in men. J Gerontol 50A: 101–106, 1995.
126. Roberts SB. Energy regulation and aging: recent findings and their
implications. Nutr Rev 58: 91–97, 2000.
127. Roberts SB. High glycemic index foods, hunger and obesity: is
there a connection? Nutr Rev 58: 163–169, 2000.
128. Roberts SB. Influence of age on energy requirements. Am J Clin
Nutr 62 Suppl: 1053A–1058A, 1995.
129. Roberts SB. Use of the doubly labeled water method for measurement of energy expenditure, total body water, water intake, and
metabolizable energy intake in humans and small animals. Can
J Physiol Pharmacol 67: 1190 –1198, 1989.
130. Roberts SB and Dallal GE. The effects of age on energy balance.
Am J Clin Nutr 68: 975S–979S, 1998.
131. Roberts SB, Fuss P, Dallal GE, Atkinson A, Evans WJ, Joseph
L, Fiatarone MA, Greennberg AS, and Young VR. Effects of age
on energy expenditure and substrate oxidation during experimental overfeeding in healthy men. J Gerontol 51A: B148 –B157, 1996.
132. Roberts SB, Fuss P, Heyman MB, Evans WJ, Tsay R, Rasmussen H, Fiatarone M, Cortiella J, Dallal GE, and Young VR.
Control of food intake in older men. JAMA 272: 1601–1606, 1994.
133. Roberts SB, Hajduk CL, Howarth NC, Russell R, and McCrory
MA. Dietary variety predicts low body mass index and inadequate
micronutrient intakes in community-dwelling older adults. J Gerontol 60: 613– 621, 2005.
134. Roberts SB and Hays NP. Regulation of energy intake in old age.
In: Functional Neurobiology of Aging, edited by Hof PR and Mobbs
CV. San Diego, CA: Academic, 2001, p. 829 – 838.
135. Roberts SB, Heyman MB, Evans WJ, Fuss P, Tsay R, and
Young VR. Dietary energy requirements of young adult men, determined by using the doubly labeled water method. Am J Clin
Nutr 54: 499 –505, 1991.
136. Roberts SB, Nicholson M, Staten M, Sawaya AL, Heyman MB,
Fuss P, and Greenberg AS. Relationship between circulating
leptin and energy expenditure in adult men and women aged 18
years to 81 years. Obes Res 5: 459 – 463, 1997.
137. Roberts SB, Young VR, Fuss P, Fiatarone MA, Richard B,
Rasmussen H, Wagner D, Joseph L, Holehouse E, and Evans
WJ. Energy expenditure and subsequent nutrient intakes in overfed young men. Am J Physiol Regul Integr Comp Physiol 259:
R461–R469, 1990.
138. Roberts SB, Young VR, Fuss P, Heyman MB, Fiatarone MA,
Dallal GE, and Evans WJ. What are the dietary energy needs of
elderly adults? Int J Obesity 16: 969 –976, 1992.
139. Rolls BJ, Dimeo KA, and Shide DJ. Age-related impairments in
the regulation of food intake. Am J Clin Nutr 62: 923–931, 1995.
140. Rolls BJ and McDermott TM. Effects of age on sensory specific
satiety. Am J Clin Nutr 54: 988 –996, 1991.
141. Rolls BJ and Rowe EA. Variety in a meal enhances food intake in
man. Physiol Behav 26: 215–221, 1981.
142. Rolls BJ, van Duijvenvoorde PM, and Rowe EA. Variety in the
diet enhances intake in a meal and contributes to the development
of obesity in the rat. Physiol Behav 31: 21–27, 1983.
143. Roth GS. Hormone action during aging: alterations and mechanisms. Mech Ageing Devel 9: 497–514, 1979.
144. Roubenoff R, Hughes VA, Dallal GE, Nelson ME, Morganti C,
Kehayias JJ, Singh MA, and Roberts SB. The effect of gender
and body composition method on the apparent decline in lean
mass-adjusted resting metabolic rate with age. J Gerontol A Biol
Sci Med Sci 55: M757–M760, 2000.
145. Sahyoun NR, Serdula MK, Galuska DA, Zhang XL, and Pamuk
ER. The epidemiology of recent involuntary weight loss in the
United States population. J Nutr Health Aging 8: 510 –517, 2004.
146. Saltzman E and Roberts SB. Effects of energy imbalance on
energy expenditure and respiratory quotient in young and older
men: a summary of data from two metabolic studies. Aging Clin
Exp Res 8: 370 –378, 1996.
147. Sawaya AL, Fuss PJ, Dallal GE, and Roberts SB. Meal palatability, substrate oxidation and blood glucose in young and older
men. J Physiol Behav 70: 1– 8, 2001.
148. Sawaya AL, Saltzman E, Fuss P, Young VR, and Roberts SB.
Dietary energy requirements of young and older women deter-
AGING AND ENERGY REGULATION
Physiol Rev • VOL
189.
190.
191.
192.
193.
194.
195.
196.
197.
198.
199.
200.
distribution, and physical activity level. Am J Clin Nutr 61: 772–
778, 1995.
Warwick ZS, Hall WG, Pappas TN, and Schiffman SS. Taste and
smell sensations enhance the satiating effect of both a high-carbohydrate and high-fat meal in humans. Physiol Behav 53: 553–563,
1993.
Wegener M, Borsch G, Schaffstein J, Luth I, Rickels R, and
Ricken D. Effect of aging on the gastro-intestinal transit of a
lactulose-supplemented mixed solid-liquid meal in humans. Digestion 39: 40 – 46, 1988.
Weiffenbach JM, Baum BJ, and Burghauser R. Taste thresholds: quality specific variation with human aging. J Gerontol 37:
372–377, 1982.
Westerterp KR and Meijer EP. Physical activity and parameters
of aging: a physiological perspective. J Gerontol A Biol Sci Med Sci
56: 7–12, 2001.
Willis MW, Ketter TA, Kimbrell TA, George MS, Herscovitch
P, Danielson AL, Benson BE, and Post RM. Age, sex and laterality effects on cerebral glucose metabolism in healthy adults.
Psychiatry Res 114: 23–37, 2002.
Wolden-Hanson T, Marck BT, and Matsumoto AM. Blunted
hypothalamic neuropeptide gene expression in response to fasting,
but preservation of feeding responses to AgRP in aging male Brown
Norway rats. Am J Physiol Regul Integr Comp Physiol 287: R138 –
R146, 2004.
Wolden-Hanson T, Marck BT, Smith L, and Matsumoto AM.
Cross-sectional and longitudinal analysis of age-associated changes
in body composition of male brown Norway rats: association of
serum leptin levels with peripheral adiposity. J Gerontol 54: B99 –
B107, 1999.
Wolden-Hanson TB, Marck T, and Matsumoto AM. Troglitazone treatment of aging Brown Norway rats improves food intake
and weight gain after fasting without increasing nypothalamic NPY
gene expression. Exp Gerontol 37: 679 – 691, 2002.
Wooley SC and Wolley OW. Salivation to the sight and thought of
food: a new measure of appetite. Psychosom Med 35: 136 –142,
1973.
Wurtman JJ, Lieberman H, Tsay R, Nader T, and Chew B.
Calorie and nutrient intakes of elderly and young subjects measured under identical conditions. J Gerontol 43: B174 –B180, 1988.
Zhang Y, Proenca R, Maffei M, Barone M, Leopold L, and
Friedman JM. Positional cloning of the mouse obese gene and its
human homologue. Nature 372: 425– 432, 1994.
Zurlo F, Lillioja S, Puente AE, Nyomba BL, Raz I, Saad MF,
Swinburn BA, Knowler WC, Bogardus C, and Ravussin C. Low
ratio of fat to carbohydrate oxidation as predictor of weight gain:
study of 24-h RQ. Am J Physiol Endocrinol Metab 259: E650 –E657,
1990.
86 • APRIL 2006 •
www.prv.org
Downloaded from http://physrev.physiology.org/ by 10.220.33.3 on July 4, 2017
173. Stunkard AJ and Messick S. The three-factor eating questionnaire to measure dietary restraint, disinhibition and hunger. J Psychosom Res 29: 71– 83, 1985.
174. Stunkard AJ, van Itallie TB, and Reis BB. The mechanism of
satiety: effect of glucagon on gastric hunger contractions in man.
Proc Soc Exp Biol Med 89: 258 –261, 1955.
175. Sturm K, MacIntosh CG, Parker BA, Wishart J, Horowitz M,
and Chapman IM. Appetite, food intake, and plasma concentrations of cholecystokinin, ghrelin, and other gastrointestinal hormones in undernourished older women and well-nourished young
and older women. J Clin Endocrinol Metab 88: 3747–3755, 2003.
176. Sturm K, Parker B, Wishart J, Feinle-Bisset C, Jones KL,
Chapman I, and Horowitz M. Energy intake and appetite are
related to antral area in healthy young and older subjects. Am J
Clin Nutr 80: 656 – 667, 2004.
177. Surrao J, Sawaya AL, Dallal GE, and Roberts SB. The use of
food quotients in human doubly labeled water studies: does it
matter which food intake method is used? J Am Diet Assoc 98:
1015–1020, 1998.
178. Tayback M, Kumanyika S, and Chee E. Body weight as a risk
factor in the elderly. Arch Intern Med 150: 1065–1072, 1990.
179. Teff KL and Engelman K. Palatability and dietary restraint: effect
on cephalic phase insulin release in women. Physiol Behav 60:
567–573, 1996.
180. Thorne A and Wahren J. Diminished meal-induced thermogenesis in elderly man. Clin Physiol 10: 427– 437, 1990.
181. Tremblay A, Despres JP, Leblanc C, Craig CL, Ferris B,
Stephans T, and Bouchard C. Effect of intensity of physical
activity on body fatness and fat distribution. Am J Clin Nutr 51:
153–157, 1990.
182. Tuttle WW, Horvath SM, Presson LF, and Daum K. Specific
dynamic action in men past 60 years of age. J Appl Physiol 5:
631– 634, 1953.
183. Tzankoff SP and Norris AH. Effect of muscle mass decrease on
age-related BMR changes. J Appl Physiol 43: 1001–1006, 1977.
184. Van Liere EJ and Northup DW. The empyting time of the stomach of old people. Am J Physiol 134: 719 –722, 1941.
185. Vansant G, VanGaal L, VanAcker K, and DeLeeuw I. Importance of glucagon as a determinant of resting metabolic rate and
glucose-induced thermogenesis in obese women. Metabolism 40:
672– 675, 1991.
186. Vaughan L, Zurlo F, and Ravussin E. Aging and energy expenditure. Am J Clin Nutr 53: 821– 825, 1991.
187. Veyrat-Durebex C and Alliot J. Changes in pattern of macronutrient intake during aging in male and female rats. Physiol Behav
62: 1273–1278, 1997.
188. Visser M, Deurenberg P, van Staveren WA, and Hautvast
JGAJ. Resting metabolic rate and diet-induced thermogenesis in
young and elderly subjects: relationship with body composition, fat
667