CHAPTER
I
ABSTRACT
In recent decades,
life expectancy in the USA and Europe has been prolonged in men and women to
approximately 74 years and 80 years, respectively. Many factors contribute to
this development, but medical progress seems to be the most effective one. Demographical data indicate
that the elderly are the most rapidly growing segment of the population in
industrialized countries.
Age-related changes in body composition
can be considered the consequence of changes in energy and protein metabolism,
while also having a leverage effect on protein and energy requirements. Changes
in organ and systems weights obviously affect energy balance regulation.
Considered at the system level, age-related changes are numerous, but it is
still debated whether they are related to aging per se or to conditions (such
as poor nutrition, disease, drug treatments etc.) that prevail in elderly
persons. It is likely that most changes occur in the gastrointestinal,
circulatory and immune system do not affect energy and protein requirements at
rest. However, aging is associated with difficulties in adapting to new
environmental conditions that lead to stress. Repeated episodes of stress might
lead to accumulation of deficits that can affect energy and protein balances.
.
CHAPTER
II
INTRODUCTION
Metabolism
is the set of chemical reactions that happen in
living organisms
to maintain life. These processes allow organisms to grow and reproduce,
maintain their structures, and respond to their environments.
The metabolism of an organism determines which
substances it will find nutritious and which it will find poisonous. For
example, some prokaryotes use hydrogen
sulfide as a nutrient, yet this gas is poisonous to animals. The speed of
metabolism, the metabolic rate, also influences how
much food an organism will require.
Nowadays so many diseases related
with aging. So it is important for
us to understand the metabolic changes in elderly because the metabolism in young
people is different with
metabolism in elderly. In this paper I will try to explain about metabolic
changes in elderly. The material will be limited in carbohydrate metabolism,
protein metabolism and lipid metabolism.
Specifically we review glucose homeostasis, total body protein, and Adiposity
increases with age
CHAPTER
II
DISCUSSION
Carbohydrate metabolism
in the Elderly 1
The reduction in whole-body carbohydrate
metabolism in the elderly is one of the hallmarks of the aging process. Substantial
evidence has been provided showing that increasing age is associated with
decreased glucose tolerance. Figure 1 shows results of a 2h glucose tolerance
test in healthy men from the Baltimore Longitudinal Study of Aging across the
adult age span. There is a progressive decline in glucose tolerance from the
third decade through the ninth decade of age. The 2 h plasma glucose level
during an oral glucose tolerance test rises on average, 5.3 mg/dl per decade
and the fasting plasma glucose rises on average, 1mg/dl per decade. This
decline in glucose tolerance is also rejected in the NHANES III survey on the
prevalence of diabetes and impaired fasting glucose and impaired glucose
tolerance in US adults. Comparison of the percentage of physician-diagnosed diabetes
in middle-aged adults (40-49 y) and elderly adults (75 y) reveals an increase
of 3.9-13.2%. Likewise, the percentage of adults with undiagnosed diabetes (defined
as a fasting plasma glucose _126 mg/dl) rises from 2.5% to 5.7% and the
percentage of adults with impaired fasting glucose (defined as a fasting plasma
glucose of 110-125 mg/dl) rises from 7.1% to 14.1%. Therefore, approximately a
third of the elderly adults in the US have abnormal glucose tolerance as defined
by the American Diabetes Association.
Glucose Homeostasis 4
Increasing
age results in a progressive deterioration in the number and the function of
insulin producing beta cells. The capacity of these cells to recognize and
respond to changes in glucose concentration is impaired. In elderly subjects a greater
proportion of the insulin released into the circulation in response to a
glucose challenge is in the form of the inactive precursor proinsulin than in
their younger counterparts. Of perhaps even greater importance is the
development of progressive peripheral insulin resistance with age. Compared
with younger persons the elderly have a relative decrease in lean body mass
with a relative increase in adiposity. Since little change in the total number
of fat cells occurs with age, the increased adiposity appears due to an
increase in fat cell size. In general, as adipocytes enlarge they turn down
their insulin receptors. Thus, even in nonobese elderly persons there is peripheral
insulin resistance due to increased size of adipocytes with a relative decrease
in insulin receptors. The combination of abnormal beta cell function with peripheral
insulin resistance leads to increased glucose intolerance in normal aged
persons. Figure 2 is a nomogram for correcting the
glucose tolerance test for the age of the patient, an important consideration
in the diagnosis of diabetes in the elderly.
Protein Metabolism in
the Elderly 2
Body composition changes as people get
older. One of the noteworthy alterations is the reduction in total body
protein. A decrease in skeletal muscle is the most noticeable manifestation of
this change but there is also a reduction in other physiologic proteins such as
organ tissue, blood components, and immune bodies as well as declines in total
body potassium and water.
A decrease in skeletal muscle is the
most noticeable manifestation of the change in body composition but there is
also a reduction in other physiologic proteins such as organ tissue, blood
components, and immune bodies as well as declines in total body potassium and
water that are not readily apparent. Total body water decreases along with the
reduction of muscle mass, but total body fat may increase proportionally. The increase
in fat tends to be noticeable because it is laid down in the truncal area,
increasing fat tissue around organs and thickening the torso.
The most notable metabolics change
associated with a reduction of muscle mass is a decrease in energy
requirements. The most metabolically active body compartment is protein tissue
and when the protein compartment is reduced in mass, then basal energy
requirements needed to maintain the protein tissue decreases. The reduction of
protein compartments, including red blood cells, white blood cells, platelets,
stem cells, antigens, antibodies, hormones, enzymes and others, contributes to impaired wound
and fracture healing, loss of skin elasticity, an inability to fight infection,
muscle weakness potentially leading to falls, decreases in functional capacity,
and an inability to maintain tissue integrity. These changes may have a
profound effect on the health and well-being of older adults. Although it will take
longer for older patients to return to pre-injury status, they can heal wounds
and repair fractures although it will still require more time for older
patients to return to baseline status than it will for younger adults; if there
is a deficit of protein and energy, it will take even longer. Older adult
patients may also develop pressure ulcers rapidly due to a lack of adequate subcutaneous
fat pads, skin fragility, and poor muscle tissue integrity.
Ward and Richardson (1991) have
extensively reviewed changes in liver protein metabolism with age. It appears
that total protein synthesis is unequivocally reduced in in vitro systems (cell
free, liver slices, cultured hepatocytes, or perfused liver). However, a large
discrepancy is reported in in vivo studies. With respect to specific proteins,
out of 500 or more proteins synthetized in the liver, only about 10 have been
shown to be either increased or decreased. This aspect of specific proteins is
a matter of great interest in humans. Fu and Nair (1998) have demonstrated an
age related
reduction in fibrinogen fractional synthesis rate, while that of albumin is
unchanged. However, absolute synthesis rates did not differ and Boirie et al
(1998) have demonstrated a similar albumin and fibrinogen synthesis response to
feeding. These observations suggest that the increased postprandial utilization
of aminoacids by splanchnic tissues (Boirie et al, 1997) cannot be fully explained
by changes at the liver level. Apparently, there is no demonstrated age-related
change in protein degradation in the liver. This is however in conflict with
the constancy of protein concentration in liver cells, which suggests that protein
degradation should be decreased to match reduced synthesis. In humans, Fu and
Nair (1998) have suggested that protein degradation in the liver is reduced
with age since fibrinogen concentrations tend to increase. Therefore, although
liver is a key metabolic organ changes in protein and energy metabolism in the
liver, induced by age, are likely to be of little consequence at the whole body
level in standard conditions.
Lipid
metabolism in the elderly 2
Adiposity increases with age. The size
of the adipose tissue mass is determined by the balance between the recruitment
of lipid substrates (i.e. free fatty acids) from adipose tissue and their
subsequent oxidation by respiring tissues. Thus, change in the liberation of
free fatty acids from adipocytes, the capacity of respiring tissue to oxidize
free fatty acids or a combination of both may contribute to the age-related
increase in body fat.
Body fat accumulation, especially in the
abdominal region, increases the risk for cardiovascular disease and diabetes in
the elderly. Understanding the mechanisms regulating changes in adiposity with
age has important public health implications.
That age is associated with a reduced
capacity to mobilize free fatty acids from adipose tissue stores. Reduced free
fatty acid mobilization may, in turn, decrease fat oxidation by limiting
substrate supply. However, when the age-related impairment in free fatty acid
mobilization is examined in the context of the energy demands of the body, a
different conclusion is reached. That is, when examined relative to the energy
needs of the body, free fatty acid release is not impaired in the elderly. In
fact, free fatty acids are released in excess of energy needs in older
individuals when compared to younger controls. For example, under resting
conditions, free fatty acid rate of appearance is greater in older men and
women despite reduced resting energy expenditure. Moreover, during exercise of
the same caloric expenditure, the rate of appearance of free fatty acid was
greater in older compared to younger individuals. Finally, following a brief
fast, the rate of appearance of palmitate was 26% higher in older compared to
younger individuals when expressed relative to lean body mass, the
metabolically active component of body mass. Thus, when considered relative to
the energy demands of the body or the metabolically-active tissue mass, aging
is not associated with impaired free fatty acid release.
The mechanisms underlying the
age-related increase in free fatty acid release relative to the energy demands
of the body are not known. In humans, the release of free fatty acids is
primarily regulated by inhibitory modulators, such as insulin. Aging is
associated with reduced sensitivity to the anti-lipolytic effect of insulin in
isolated adipocytes. Moreover, in vivo studies show that both the time course
for the suppression of plasma free fatty acids and the dose ± response
suppression of free fatty acid appearance by insulin are diminished with age.
Thus, resistance to the anti-lipolytic effect of insulin may account for the
excess release of free fatty acids in older individuals. It should be pointed
out, however, that increased free fatty acid release in older individuals may
simply result from increased adipose tissue mass. Indeed, the rate of appearance of free
fatty acids is
either similar between older and younger individuals or greater in younger
individuals when expressed per unit adipose tissue mass. Whatever the
mechanism, reduced free fatty acid availability secondary to diminished release
of free fatty acids from adipose tissue does not appear to be a factor
contributing to reduced fat oxidation with age.
Consequences of
age-related changes in lipid metabolism
The picture that emerges from the above
discussion of changes in lipid metabolism with age is one of increased
availability of free fatty acids in excess of the energy needs or the oxidative
capacity of fat-free tissue (Figure 2).
Figure 2
Age-related changes in adipose tissue free fatty acid release, capacity of
tissues to oxidize free fatty acids and the metabolic effects of non oxidized
free fatty acids. Aging is associated with an increase in adipose tissue mass
and a reduction in the mass of oxidative tissue and its capacity to oxidize fat
(O2). The increased release of free fatty acids in older individuals in excess
of the energy needs and=or oxidative capacity of respiring tissues increases
the amount of non-oxidized free fatty acids. Excess non-oxidized free fatty
acids with age may have several adverse metabolic effects.
Aside from the effects that these
changes in lipid metabolism may have on body fat accumulation, their immediate
consequence is to increase plasma free fatty acid concentration and or the
non-oxidative disposal of free fatty acids. Increased plasma free fatty acid
concentration and increased non-oxidative disposal have several adverse
consequences.
An increase in plasma free fatty acid
concentration could lead to increased glucose production, impaired
insulin-stimulated glucose uptake and decreased hepatic insulin extraction. Together,
these changes would have the net effect of promoting the development of
hyperinsulinemia and insulin resistance. The primary route for the
non-oxidative disposal of free fatty acids is incorporation into
triglyceride-rich VLDL particles in the liver. Thus, increased non-oxidative
disposal of free fatty acids with age would contribute to the development of an
atherogenic lipid profile. Collectively, changes in lipid metabolism with age
that contribute to increased plasma free fatty acid concentrations or increased
non oxidative disposal may contribute to increased risk for the development of
diabetes and cardiovascular disease. Interventions that increase the capacity
of respiring tissues to utilize free fatty acids, therefore, may be beneficial
in preventing the development of chronic disease in the elderly.
CHAPTER
III
CONCLUSION
Age has
profound effects on glucose homeostasis approximately 18.8% of the US
population between the ages of 60 and 74 are diabetic. Another 14% have
impaired fasting glucose. These age-related changes in body composition are
responsible for a large portion of the decline in glucose tolerance seen in the
elderly. They are also potentially modifiable through a prudent combination of
diet and exercise.
Although
free fatty acid release is impaired with age under a number of experimental
conditions, when examined relative to the energy needs of the
metabolically-active tissue, the release of free fatty acids is actually
greater in older compared to younger individuals. Thus, free fatty acid
availability does not appear to be rate limiting for fat oxidation. Instead, a
reduction in the size and/or oxidative capacity of the metabolically-active
tissue mass is probably a more likely determinant of reduced fat oxidation. The
reduction in oxidative capacity of skeletal muscle with age, however, does not
appear to be an immutable consequence of the aging process
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2.Lipid metabolism in the
elderly. Available at: http://www.nature.com/ejcn/journal/v54/n3s/pdf/1601033a.pdf.
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3. Protein and older
adult. Available at: http://www.jacn.org/cgi/reprint/23/suppl_6/627S.pdf.
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4.
Age-Related
Physiological Changes and Their Clinical Significance. Available at: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1273316/pdf/westjmed00220-0011.pdf.
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