Aging of the Nervous, Locomotive, Cardiovascular, Respiratory, Digestive, Urinary and Hematopoirtic Systems
Abstract
Aging is a slowly progressive natural process that is associated with
adverse effects on different system organs. It induces changes in
nearly every tissue in the body. Reactive oxygen species and
mitochondrial damage are still the accepted two theories of aging.
Age-related diseases include dementia and Alzheimer's disease,
osteoarthritis and osteoporosis, hypertension, atherosclerosis and heart
failure, chronic obstructive pulmonary disease and emphysema,
hyperchlorhydria, hepatitis and hepatocellular carcinoma,
glomerulosclerosis and chronic kidney disease, anemia and increased rate
of carcinogenesis. Biomarkers of aging are available. Exercise, caloric
restriction and drug dose modifications are recommended in the elderly.
Abbreviations: AD: Alzheimer's Disease;
ApoE: Apolipoprotein E; BBB: Blood-Brain Barrier; BCSFB:
Blood-Cerebrospinal Fluid Barrier; CF: Cystic Fibrosis; CKD: Chronic
Kidney Disease; COPD: Chronic Obstructive Pulmonary Disease; CR: Caloric
Restriction; CVD: Cardiovascular Disease; EE: Energy Expenditure; GH:
Growth Hormone; HF: Heart Failure; IGF-I: Insulin-like Growth Factor-1;
JOA: Japanese Orthopaedic Association; NPC: Niemann-Pick Type C; RNS:
Reactive Nitrogen Species; ROS: Reactive Oxygen Species; SA:
Sino-Atrial, SSA: Senile Systemic Amyloidosis; TRH:
Thyrotropin-Releasing Hormone
Introduction
Aging is described as a multifactorial, complex, progressive, natural
and irreversible process that is injurious to the human body. Apart
from immuno-senescence and age-related reproductive changes which we
have previously reviewed [1,2], aging has a negative impact on nearly
every tissue and organ in the body Globally, increased longevity has
been accompanied by increased incidence of age-related diseases which
represent a costly burden on healthcare services. The etiology of aging
is still not fully explained. Reactive oxygen species (ROS) and
mitochondrial theories are the two valid theories of aging. Mitochondria
are the major site for production of ROS in the cell. The vicious
circle of oxidative stress theory includes that inside the mitochondria
ROS induces mitochondrial damage and accumulation of oxidative damage
particles which in turn increases the liberation of ROS, leading to more
mitochondrial damage.
ROS impairs organ functions and increases the morbidity and mortality
rates. ROS-related aging is mentioned to be ameliorated by general
hygiene as well as environmental, nutritional and drug remedies [3-5].
Oxidative stress occurs when there is an oxidants/ antioxidants
imbalance [6]. ROS and reactive nitrogen species (RNS) are reported to
be predominantly harmful but to lesser extent beneficial to tissues and
organs [7]. Genetic and environmental factors contribute to the type and
rate of functional decline with aging and to the development of
age-associated diseases [8]. Air and water pollution, tobacco and
alcohol, heat and cold, medications and chemicals, pesticides and
radiation are mentioned as harmful factors in the elderly [9]. These
toxicants induce oxidative stress leading to reduction of the
regenerative capacity of the stem cells and enhancement of aging [10].
Autophagy is fundamental to maintain organ function through elimination
of accumulated damaged particles; thus, prolonging lifespan [11].
Autophagy becomes less efficient with age [12]. Apolipoprotein E
(ApoE) is greatly involved in age-related inflammation and
atherosclerosis, and in rheumatoid arthritis, macular degeneration and
cancer [13]. Oral or parental thyrotropin-releasing hormone (TRH) has
proved to possess an antiaging property in old mice, it increased the
testicular weight, structure and function and cured renal amyloid and
hyaline degenerations [14]. Aging is reported to start at the age of
30-40. It induces alterations in organs of the nervous, locomotive,
cardiovascular, respiratory, digestive, urinary, and hematopoietic
systems. These organ changes could be aggravated into diseases that
develop even in healthy elderly [15].
Aging of the Nervous System
Aging of the brain is assumed to be the referee of death, it finally
leads to neurodegeneration and dementia [16]. Health condition of
patients with highly impaired cognitive function and coming from
unhealthy families is reported to be worse than that of individuals with
less impaired cognition [17]. Aging worsens human brain function due to
the release of ROS. Flavonoids in foods are antioxidants that delay the
age-related decline of cognitive functions and the development of
neurodegenerative diseases [18]. Blood-brain barrier (BBB) and
blood-cerebrospinal fluid barrier (BCSFB) are documented to play a great
role in the progression of age-associated neurodegeneration and
Alzheimer's disease [19]. Age-related Alzheimer's disease (AD) is
associated with silent microbleeds from small cerebral blood vessels and
with stiffness of the aorta and great arteries [20]. The co-incidence
of AD and osteoporosis increases in the elderly. In these two
degenerative diseases. amyloid plaques and aggregations are deposited in
the brain and in the skeletal elements. Vitamin D deficiency is
diagnosed in AD or AD with osteoporosis [21].
Aging also results in disturbances in the autonomic nervous system.
In aging rats, significant changes were demonstrated in the sympathetic
noradrenergic innervation of the thymus, spleen, and mesenteric lymph
nodes resulting in immunosuppression [22]. Age-related tachycardia,
constipation, erectile dysfunction, fluid retention, systemic
inflammation, type-2 diabetes mellitus, insomnia, AD, atherosclerosis,
and cancer are consequences of loss of the parasympathetic function and
unmasking of the basic sympathetic function [23]. Motor neurons and
innervated muscle fibers exhibit age-related decline in number in
addition to muscle fiber atrophy [24].
Aging of the Locomotive System
With aging, there is a diminished function of the skeletal muscles
leading to decreased physical fitness, sarcopenia, frailty and
eventually disability thus, independence and quality of life are
affected in the elderly [25]. Sarcopenia is reported to begin at the
fourth decade of life and to be featured by decreased muscle mass and
strength, decreased total body protein and decreased muscle and
mitochondrial protein synthesis. Mitochondria plays a crucial role in
aging of the skeletal muscles [26]. Exercise is recommended in both
young and older individuals, it increases muscle strength but does not
correct all age-induced changes [27]. Vitamin D supplements are
prescribed to the elderly to protect against the incidence of
osteoporosis [28]. The Japanese Orthopaedic Association (JOA) provides
loco-check and loco-training programs to minimize the incidence of the
geriatric locomotive syndrome in the elderly suffering from joint
disorders [29]. Aging is also associated with a decline in the levels of
growth hormone (GH) and serum insulin-like growth factor-1 (IGF-I)
resulting in osteoporosis and muscle atrophy. GH and IGF-I supplements
are also recommended for the elderly [30].
Aging of the Cardiovascular System
Aging is associated with diminished elasticity of the arterial tree,
decreased left ventricular diastole, declined function of the
sino-atrial (SA) node and decreased effect of beta-adrenergic
stimulation. Old patients with cardiovascular disease (CVD) are prone to
develop heart failure (HF) [31]. HF is a multiple organ disease, it
increases with aging, most likely due to increased insulin/ IGF-1
signalling and due to reduced functions of extracardiac organs [32].
Accumulation of ROS, with aging, increases the vulnerability to CVD and
heart failure [33].
Aging of the Respiratory System
With aging, the respiratory system exhibits a decrease in gas
exchange area, respiratory volumes and maximal oxygen consumption. Lung
is one of the most important sites to show amyloid deposition in senile
systemic amyloidosis (SSA). In pulmonary amyloidosis of the elderly,
autoptic lung specimens demonstrated abnormal amyloid deposits around
the bronchi, bronchioles, alveoli and pulmonary vessels but not around
lymphatics [34]. In Niemann-Pick Type C (NPC) disease, caused by
deficiency of either of NPC1 or NPC2 proteins, accumulation of
unesterified cholesterol was observed in the lungs of mice; the disease
had started early in the lungs, preceded other tissues and worsened with
the advance of age [35].
Chronic obstructive pulmonary disease (COPD) is 2-3 times more
frequent above the age of 60 years than in younger population. Aging
elevates basal levels of inflammation and oxidative stress
(inflammaging) and increases immuno-senescence [36]. Environmental
gases, like cigarette smoke and kitchen vapours, are thought to enhance
aging of the lungs via reduction of the resolution of inflammation,
diminution of the anti-oxidant capacity and failure of disposal of
damaged proteins; eventually leading to aggravation of COPD [37,38].
With aging, senile emphysema entails dilatation of the alveolar spaces
and decreased lung elasticity, whereas COPD includes destruction of the
alveolar walls and fibrosis of the respiratory passages [39]. Moreover,
cystic fibrosis (CF) of lungs in adults is augmented with the advance of
age leading to more decline in lung functions [40].
Aging of the Digestive System
Aging of the gastrointestinal tract in man is featured by prevalence
of gastric atrophy and hypochlorhydria because of Helicobacter pylori
infection and constipation. Constipation is thought to be mainly caused
by the sedentary lifestyle and diet rather than by aging process. With
aging there are decreased motility, weakened mucosal barrier and
increased incidence of colonic cancer [41]. Aged patients with liver
diseases exhibit significant decrease in liver volume and blood flow
thus, increasing vulnerability to drug-induced hepatitis, viral
hepatitis, autoimmune liver diseases and hepatocellular carcinoma [42].
Aging impairs the well-known regenerative capacity of the liver
following partial hepatectomy due to decreased cell cycle as well as
increased apoptosis and autophagy. Old mice, when compared to young
ones, showed significant reduction in the relative liver/body weight
ratio and marked elevation of liver cell damage markers at 48 h and 72 h
after partial hepatectomy [43]. In rats, aging of the liver was
observed to be associated with increased uptake function and decreased
metabolic function of the hepatocytes but the excretory function was
unaffected [44].
Aging of the Kidneys
Aged kidneys suffer from decreased renal blood flow and glomerular
filtration rate, decreased tubular ability to conserve and dilute urine,
and diminished ability to regulate the pH and serum sodium level. The
age- related changes that occur in the kidneys are the results of
natural organ senescence and atherosclerosis or diabetes mellitus that
are commonly associated with aging
[45] . Glomerulosclerosis as a part of vascular aging is the cause of
frequent incidence of chronic kidney disease (CKD) in the elderly
[46] .
Aging of the Hematopoietic System
Aging induces alterations in the hematopoietic stem cells and
progenitors leading to anemia, immuno-senescence, and myeloid diseases
[47]. Organ-specific changes in the levels of ferritin (protein) and
ferritin-bound iron have been reported pointing out to different
pathways selected by different organs to keep pace with aging. In old
rat spleens and livers, these levels were greater than in young rats
whereas in the tongues, sternohyoid muscles and esophagus were lower
than in young rats; in the larynx the levels were the same in both young
and old animals [48].
Aging and Caloric Restriction
Total energy expenditure (EE), in man, is decreased with the advance
of age due to reductions in activity and resting metabolic rate (RMR).
The reducted RMR is most likely caused by a diminution in the mass of
individual organs and reduction of the metabolic rates of individual
tissues, favoring increased fat mass and reduced lean mass [49,50].
Advanced glycation end products (AGEs), especially produced in abnormal
glucose metabolism and over-ingested in foods, are elevated in the
circulation of the elderly leading to increased incidence of chronic
diseases. Dietary restriction of AGEs and drug treatment with
AGE-inhibitors and AGE-breakers are recommended [51]. Caloric
restriction (CR) was found to prevent age-related diseases and to extend
life-span in most animals, it has an anti-inflammatory effect,
modulates mitochondrial activity and reduces oxidative damage [52].
Prolonged CR or rapamycin treatment had increased the proliferation of
the hippocampal neural stem and progenitor cells (neurogenesis) in the
brain dentate gyrus of aging female mice, leading to improvement of age-
related cognitive deficits [53]. Obesity enhances the development of
age-related cardiovascular, respiratory and musculoskeletal diseases,
type 2 diabetes mellitus, and some types of cancer [54]. Preadipocytes
constitute about 15-50�x0025; of cells in fat tissue and can give rise
to newly formed fat cells. Age-related changes in preadipocyte function
can contribute to age-related fat tissue redistribution and metabolic
diseases.[55].
Aging and Cancer
It has been observed that carcinogenesis is enhanced with age in both
man and experimental animals. Aging facilitates the progression of
cancer through: accumulation of damaged cells in the tissues and
alterations in immune and endocrine homeostatic mechanisms [56,57].
Aging and Drugs
Elderly patients are greatly affected by the frequently prescribed
psychotropic drugs (like benzodiazepines, antidepressants,
antipsychotics and lithium), and cardiovascular drugs (like warfarin,
diuretics and p-blockers). Dose adjustment of these pharmaceuticals is
mandatory in the elderly [58]. Aging increases body fat and decreases
total body water and lean mass. Consequently, hydrophilic drugs have a
smaller while lipophilic drugs have a larger volume of distribution and a
prolonged half-life. Added to this, aging is associated with a decline
in renal function. Therefore, the old drug dosing aphorism " start low,
go slow in elderly" becomes now valid [59].
Aging Biomarkers
Aging is typically associated with an increase in the production of
pro-inflammatory cytokines and inflammatory markers (inflammaging) [60].
Biomarkers of aging are available to determine the biological age of
individuals and organs, to assess the influence of various determinants
and interventions on the rate and type of aging, and to evaluate life
expectancy and future rate of morbidity [61]. There are biomarkers of
the cardiovascular system, metabolic processes, inflammation,
hypothalamic-pituitary activity, sympathetic nervous system, and
individual organ functioning (like kidney, lung, liver and heart) [62].
Conclusion
An adequate knowledge of the etiology and adverse effects of aging is
necessary to understand the derangement that occurs in individual
system organs, to avoid unnecessary morbidity and disabilities, and to
improve the quality life in the elderly.
Switching from Allopurinol to Febuxostat:
A Comparison of The Rate of Renal Functional
Decline in Patients With Moderate and Severe
Chronic Kidney Disease - https://biomedres01.blogspot.com/2020/02/switching-from-allopurinol-to.html
More BJSTR Articles : https://biomedres01.blogspot.com
No comments:
Post a Comment
Note: Only a member of this blog may post a comment.