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Aging Syndrome
Mehmet Rami
Helvaci (1)
Orhan Ayyildiz (1)
Orhan Ekrem Muftuoglu (1)
Mustafa Yaprak (2)
Abdulrazak Abyad (3)
Lesley Pocock (4)
(1) Professor
of Internal Medicine, MD
(2) Assistant Professor of Internal Medicine,
MD
(3) Middle-East Academy for Medicine of Aging,
Chairman, MD, MPH, MBA, AGSF
(4) medi-WORLD International
Correspondence:
Mehmet
Rami Helvaci
Professor of Internal Medicine, MD
ALANYA, Antalya,
Turkey
Phone:
00-90-506-4708759
Email: mramihelvaci@hotmail.com
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Abstract
Aging
syndrome or accelerated endothelial damage
syndrome or metabolic syndrome is a chronic
inflammatory process on vascular endothelium
both at arterial and venous systems of
the body. It terminates with an accelerated
endothelial damage, an accelerated atherosclerosis,
end-organ insufficiencies, early aging,
and death. Male sex, sedentary life style,
animal-rich diet, overweight, obesity,
smoking, alcohol, white coat hypertension,
hypertension, impaired fasting glucose,
impaired glucose tolerance, diabetes mellitus,
hypertriglyceridemia, dyslipidemia, chronic
infections, chronic inflammations, chronic
depression, cancers, overuse of the body,
and sickle cell diseases may be the major
parameters of the metabolic syndrome.
Cirrhosis, chronic obstructive pulmonary
disease, chronic renal disease, myocardial
infarction, stroke, early aging, and death
may be the main terminal end-points of
the syndrome. As a conclusion, calendar
ages should not be accepted as the real
physiologic ages of patients with the
above parameters and terminal end-points
of the metabolic syndrome. On the other
hand, long term underweight in the absence
of any pathology such as anorexia nervosa,
sudden weight loss, malignancies, chronic
infections, chronic inflammations, or
chronic depression may even decelerate
the aging by decreasing insulin resistance,
mean arterial blood pressure, and vascular
endothelial damage and it may be a good
property for a long lifespan.
Key words: Aging
syndrome, accelerated endothelial damage
syndrome, metabolic syndrome
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Aging syndrome or accelerated endothelial damage
syndrome or metabolic syndrome is a chronic
inflammatory process on vascular endothelium
both at arterial and venous systems of the body.
It terminates with an accelerated endothelial
damage, an accelerated atherosclerosis, end-organ
insufficiencies, early aging, and death (1-2).
All factors accelerating the normal aging process
may mainly act on vascular endothelium and they
should be accepted as components of the metabolic
syndrome. If we can define parameters of the
metabolic syndrome exactly, we can prevent the
accelerated aging process. Sedentary life style,
animal-rich diet, and excess weight may be the
most common parameters of the syndrome. Overweight
and obesity may cause a low grade inflammation
on vascular endothelium that can be shown by
slightly increased C-reactive protein levels
in patients. Although main targets of the syndrome
may be both the afferent and efferent vascular
endothelial cells, afferent blood vessels including
capillaries may be much more affected due to
their much higher blood pressure. Mean arterial
blood pressure may be one of the significant
causes of endothelial damage and it may mostly
be affected by excess weight induced changes
of the body. Excess adipose tissue acts as an
endocrine organ anywhere in the body and induces
insulin resistance. Therefore limitation of
excess weight as abdominal obesity may be meaningless
in definition of the metabolic syndrome. Actually
excess weight should be defined by means of
body mass index. Although mean body weight is
greater in males due to their tallness, body
mass index is greater in females as a more valuable
indicator of excess fat in the body. On the
other hand, long term underweight in the absence
of any pathology such as anorexia nervosa, sudden
weight loss, chronic infections, chronic inflammations,
malignancies, or chronic depression may decelerate
aging by decreasing insulin resistance, mean
arterial blood pressure, and vascular endothelial
damage, and it may be a good property for a
long lifespan.
Smoking and alcohol are the other frequent parameters
of aging syndrome or accelerated endothelial
damage syndrome or metabolic syndrome since
they cause severe endothelial damage not only
in the vasculature of respiratory and gastrointestinal
tracts but all over the body (3-4). Smoking
and alcohol have similar adverse effects on
vascular endothelium with different severity
in different organs (5-7). Smoking causes cirrhosis
too and alcohol also causes chronic obstructive
pulmonary disease. Both of them affect both
arterial and venous endothelial cells of the
body. Smoking causes a chronic inflammatory
process in the respiratory tract, lungs, and
vascular endothelium all over the body, terminating
with an accelerated atherosclerosis, end-organ
insufficiencies, early aging, and death. Therefore
it must be included among the parameters of
the metabolic syndrome. On the other hand, smoking-induced
weight loss is probably related with the smoking-induced
endothelial inflammation all over the body,
since loss of appetite is one of the major symptoms
of inflammations in the body. In another explanation,
smoking-induced loss of appetite is an indicator
of being ill instead of being healthy during
smoking (8-10). Buerger's disease (thromboangiitis
obliterans) alone is clear evidence to show
the strong atherosclerotic effects of smoking
since this disease has not been shown in the
absence of smoking. Similarly, the alcoholic
cirrhosis alone is clear evidence to show strong
atherosclerotic effects of alcohol. Alcohol
causes a chronic inflammatory process in the
gastrointestinal tract, liver, and vascular
endothelium all over the body terminating with
early aging and death therefore it must also
be included among parameters of the metabolic
syndrome.
Male sex alone may also be a significant factor
for the accelerated atherosclerotic process
of the metabolic syndrome since females live
longer all over the world (11). Fear to protect
his family is a feature of male sex in human
beings and in all animal kinds. The feature
probably comes from testosterone. You cannot
see some females fighting with each other for
a male but you can easily see some males fighting
for a female in human beings and in animal species.
You can see soldiers or coalmine workers in
males but not in females. Males use their physical
force more in daily life. The dominant physical
role of male sex is also seen during sexual
activities. The overuse of body probably comes
as an accelerated atherosclerosis and a shortened
lifespan in males in front. The shortened survival
of male sex has even been shown in the sickle
cell patients although their significantly shorter
mean life expectancy may be caused by the current
health services (12). Smoking and alcohol consumption
are also more common in males all over the world
which may also indicate presence of some additional
pressures in society on them. But the longer
lifespan of females cannot be explained by the
strong atherosclerotic effects of smoking and
alcohol alone. Effects of testosterone may also
be important in the shortened survival in males.
So the dominant role of male sex, and smoking
and alcohol put them into the accelerated atherosclerotic
process whereas excess weight is the major problem
in females concerning the accelerated aging
process. In other words, overuse of the body
in males and underuse of the body in females
may accelerate the endothelial damage, atherosclerosis,
early aging, and death. Avoidance of smoking,
alcohol, and excess weight are essential in
protection from metabolic syndrome. The term
of regular exercise should be replaced with
daily and essential activities in the protection
of females since they actually need a lifestyle
change instead of exercise. Avoidance of animal-rich
diet, walking as much as possible in a day,
avoidance of using elevators, eating fruit even
with its peel to escape chronic constipation,
drinking black tea, finding regular daily responsibilities,
finding news targets to live, and forgetting
to use taxis should be thelifestyle of people
in risk of metabolic syndrome.
Chronic infections such as tuberculosis and
bronchiectasis, chronic inflammations such as
rheumatoid arthritis and sickle cell diseases,
chronic depression, and cancers induce an accelerated
endothelial damage, an accelerated atherosclerosis,
early aging, and death therefore they should
also be included among the parameters of the
aging syndrome or accelerated endothelial damage
syndrome or metabolic syndrome. If possible,
they should be treated effectively and indicators
of the systemic inflammation including acute
phase reactants should be normalized in serum
since the systemic inflammatory processes damage
vascular endothelial cells further.
An accelerated atherosclerotic process may be
the major pathology in the metabolic syndrome
and it may be the main cause of early aging
and death (13). Atherosclerosis is more important
than venosclerosis concerning the clinical manifestations
due to the rich collaterals of venous systems
in the body. Actually, vascular endothelial
damage develops in all arterial and venous systems
of the body. Of couse much higher blood pressure
of the arterial systems is also important for
the enhanced endothelial damage in the afferent
vasculature. But hyperglycemia, sickle cell
diseases, dyslipidemia, smoking, alcohol, and
activated immune cells in chronic infections,
inflammations, and cancers also damage venous
endothelium in addition to the arterial one.
Eventually, the syndrome terminates with end-organ
insufficiencies such as cirrhosis, chronic obstructive
pulmonary disease, chronic renal failure, myocardial
infarction, and stroke, clinically (14). Hepatosteatosis,
hepatomegaly, and left lobe hypertrophy are
probably some of the significant indicators
of the metabolic syndrome in the liver (15).
Not only alcohol, but also smoking, overweight,
obesity, hypertriglyceridemia, dyslipidemia,
white coat hypertension, hypertension, and diabetes
mellitus probably have cumulative effects in
the development of them via an accelerated endothelial
damage in the liver (16). Chronic renal disease
may be one of the other indicators of the metabolic
syndrome. Smoking, alcohol, animal-rich diet,
excess weight, dyslipidemia, hypertension, and
diabetes mellitus probably have cumulative effects
in the development via accelerated endothelial
damage in kidneys. These factors cause a chronic
low grade inflammation on vascular endothelium
terminating with an accelerated atherosclerosis.
Stroke and myocardial infarction are found among
the major terminal end-points of the metabolic
syndrome since neurons and myocardial cells
do not have the ability of regeneration. Actually
these hypoxic events develop in all organs of
the body but they are able to regenerate. Chronic
obstructive pulmonary disease is also found
among the terminal end-points of the metabolic
syndrome. Not only smoking and air pollution,
but also alcohol, excess weight, dyslipidemia,
hypertension, and diabetes mellitus probably
have cumulative effects in the development via
accelerated endothelial damage in lungs.
Male sex, sedentary life style, animal-rich
diet, overweight, obesity, smoking, alcohol,
white coat hypertension, hypertension, impaired
fasting glucose, impaired glucose tolerance,
diabetes mellitus, hypertriglyceridemia, dyslipidemia,
chronic infections, chronic inflammations, chronic
depression, cancers, overuse of the body, and
sickle cell diseases accelerate the normal aging
process via an accelerated atherosclerotic process
all over the body. Therefore the individuals
with the above problems are actually elder than
their calendar ages, physiologically. Pack-year
of smoking should be added to calendar ages
to calculate physiological ages of the patients.
Drink-year of alcohol should be added to calendar
ages of the patients to calculate their physiological
ages in the syndrome. Already developed diabetes
mellitus, hypertension, cirrhosis, chronic obstructive
pulmonary disease, chronic renal disease, coronary
heart disease, and other end-organ insufficiencies
also increase the calendar ages in the syndrome.
Sickle cell diseases may be the prototypes for
the terminal end-points of the syndrome (17-18).
We can observe the terminal consequences of
disseminated endothelial damage in early years
of age in the sickle cell patients. Disseminated
endothelial damage may probably be the main
cause of accelerated aging in the sickle cell
diseases. Although arterial involvement is prominent
in the metabolic syndrome, venous involvement
is also seen in the sickle cell diseases due
to the hard red blood cells induced endothelial
damage. Physiologic ages of patients with sickle
cell diseases are much higher than their calendar
ages due to the hard red blood cells induced
endothelial damage all over the body. The hard
red blood cells damage vascular endothelial
cells especially at the capillary level since
the capillary systems are the main distributors
of the hard cells into the tissues (19). An
accelerated metabolic syndrome-like picture
is seen in the sickle cell patients in their
much earlier years of age since the accelerated
endothelial damage initiates just after birth
in their bodies.
Metformin should be the first drug to treat
the metabolic syndrome. The main action of metformin
is the loss of appetite. Although metformin
provides significant weight loss in most cases,
approximately 30% of patients cannot continue
to use it due to the loss of appetite since
they like eating. Metformin should not be used
in patients above the age of 70 years together
with multiple diseases. It should be used in
patients in those we can see the benefits of
weight loss in the longterm. Up to now, we have
not seen any significant side effects of metformin.
Thus it is found among one of the most prescribed
drugs in the world today. Since metformin decreases
body weight by suppressing the appetite, it
also decreases blood pressure and serum triglyceride
levels. Actually, metformin should be the drug
of treatment for white coat hypertension in
cases of overweight or obesity. Hypertriglyceridemia
and dyslipidemia should also be treated with
metformin in patients with overweight or obesity.
Low dose aspirin and metformin should be initiated
in all patients with overweight and obesity
above the age of 50 years to prevent development
of irreversible end-points of metabolic syndrome
such as diabetes mellitus, hypertension, stroke,
and other end-organ insufficiencies.
Acarbose should be the second choice of drug
for the treatment of metabolic syndrome in case
of metformin intolerance or insufficiency. So
acarbose can be used alone or together with
metformin. Since acarbose and metformin have
different actions in the body, their cumulative
effects will be stronger if used together. Since
acarbose decreases absorption of complex sugars
in the small intestine, it will also be useful
for the treatment of chronic constipation which
is also frequent above the age of 50 years due
to the decreased daily activities. Acarbose
is also effective on metabolic parameters including
serum triglyceride levels and mean arterial
blood pressure by decreasing body weight significantly.
If a patient cannot tolerate acarbose, it is
highly possible that the patient does not want
to use any drug since the side effects of acarbose
are very rare.
As a conclusion, male sex, sedentary life style,
animal-rich diet, overweight, obesity, smoking,
alcohol, white coat hypertension, hypertension,
impaired fasting glucose, impaired glucose tolerance,
diabetes mellitus, hypertriglyceridemia, dyslipidemia,
chronic infections, chronic inflammations, chronic
depression, cancers, overuse of the body, and
sickle cell diseases may be the major components
of the metabolic syndrome. Aging syndrome or
accelerated endothelial damage syndrome may
be other names of the syndrome. Cirrhosis, chronic
obstructive pulmonary disease, chronic renal
disease, myocardial infarction, stroke, early
aging, and death may be the major terminal end-points
of the syndrome. Finally, calendar ages should
not be accepted as the real physiologic ages
of patients with the above parameters and terminal
end-points of the syndrome. On the other hand,
long term underweight in the absence of any
pathology such as anorexia nervosa, sudden weight
loss, malignancy, chronic infections, chronic
inflammations, or chronic depression may decelerate
aging by decreasing insulin resistance, mean
arterial blood pressure, and vascular endothelial
damage and it may be a good property for a long
lifespan.
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