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Physiology of Aging - Lecture 10
Terms in this set (105)
How common is hearing problems among the elderly?
Hearing vision is very common among the elderly. It becomes more common as age increases, especially among men
age-related loss in hearing; it is progressive over time and primarily affects the ability to hear high-frequency sounds. There are greater changes in men than women
sound decibels and aging
the minimum detectable decibel level of a sound increases with aging, especially in the high-frequency ranges
the way in which we measure the amplitude of sound. Rated on a scale from 0 to 120.
Greater differences in hearing loss
begin around age 35
Possible causes of greater differences in hearing loss:
(1) work-related environmental noise, because elderly in noise-free rural areas have less hearing loss than those in urban areas
(2) hearing loss and inner ear diseases are more common in those with high cholesterol and vascular disease
Presbycusis is not associeated with:
(1) changes in the outer ear (tympanic membrane)
(2) changes in the middle ear (ossicles)
Presbycusis is often due to changes in:
(1) the inner ear (cochlea)
(2) central auditory system
How does the ear transduce sound?
(1) Sound waves vibrate the tympanic membrane (outer ear)
(2) tympanic membrane then vibrates the ossicles (small bones of the middle ear), which amplify the sound and vibrate the oval window
(3) vibration of the oval window is transferred to the fluid in the cochlea (inner ear)
(4) fluid movement causes movement of the tectotorial membrane
(5) when the tectotorial membrane moves, it bends the stereocilia of the underlying hair cells
(6) hair cells fire and send signals up hte auditory nerve, to the medulla, then on to the audityory cortex and other areas of the brain
(7) hair cells along the length of the cochlea respond to different wave-length frequencies
Types of Presbycusis:
(1) Sensory Presbycusis
(2) Neural Presbycusis
(3) Metabolic (striatal) Presbycusis
(4) Cochlear Conductive Presbycusis
What is the typical type of presbycusis
the neural or sensory type
is a major, sudden loss of hearing in the high-frequency range; only have a hard time hearing high-pitch sounds
characteristics of sensory presbycusis
(1) selective deficit in transducing high frequency sound
(2) normal speech discrimination
(3) associated with loss of hair cells of the organ of corti, particularly in the first quadrant, which is a region specialized for high frequency sound transduction
(4) these hair cells also show accumulation of lipofuscin
involves a decrease in hearing of pure tones of all frequencies, though this loss is greater in the high frequency range
characteristics of neural presbycusis:
(1) speech discrimination is typeically reduced by abou 60% of normal
(2) it is associated with loss and degeneration of hair cells and dendrites of the auditory nerve fibers
(3) associated with loss of myelin on the auditory nerve
(4) accumulation of lipofuscin is found in these cells
(5) have a hard time understanding speech
a decline in sound detection (of all sound) that increases the minimum detectable decibel level by about 30-40 dB at all frequencies
characteristics of metabolic presbycusis:
(1) it is associated with atrophy of the vascular supply to the cochlea (this is the cause)
(2) speech discrimination is not affected
(3) It is greatly affected by cardiovascular disease
Cochlear conductive Presbycusis
this is also called mechanical presbycusis, and includes some loss of hearing at all frequencies, so of all sounds, but there is greater loss at higher frequencies
characteristics of cochelar conductive presbycusis
(1) speech discrimination is not affected
(2) It is due to changes int he mechanical properties of the basilar membrane of the cochlea. This membrane thickens, especially at the base of the cochlea, and it may also have calcification and fatty deposits
(3) there is no change in hair cells or sensory neurons, so all of the hair cells are still present
this is the membrane that hair cells sit on. a healthy basilar membrane should not calcify or get stiff
Hearing in the 40s
At this time, with aging, there is a decrease in the ability to localize sound. This may be due to asymmetrical loss of hearing, meaning hearing loss in greater in one ear than in the other
Treatment for hearing loss
(1) hearing aids
(2) cochlear implants
conventional hearing aids amplify all sounds, though elderly may have a difficult time discriminating sounds in the presence of background noise. Therefore, hearing aids sometimes can provide only a limited benefit to people with hearing loss
devises that bypass the inner ear and directly stimulate the auditory nerve through a microphone that is worn on the body. Is essentially an artificial ear.
with the nervous system, the endocrine system acts to maintain homeostasis, regulate responses to internal (genes) and external signals, and controls reproduction
an organ that produces and secretes hormones that are released into the blood and act on remote target cells/tissues
endocrine glands in the human body:
pituitary, adrenals, thyroid/parathyroid, pancreas, testes, ovaries. There are other tissues of the body that have also been shown to have an endocrine function. Examples of these are fat cells and skeletal muscles.
to be a hormone...
it has to circulate in the blood so it can reach all of the tissues in the body
hormones with aging
with aging, many hormonal responses diminish. Measurement of blood level of a hormone is not a sufficient parameter to assess the function of a specific hormonal system, because of the complexity of hormone pathways. Hormone levels may be maintained, while the action/impact of the hormone may be reduced due to a diminished function of the downstream steps, like receptors, etc.
Changes that can occur in Hormonal pathways with aging:
(1) changes in the endocrine gland, especially ones involved in stress, metabolism, and glucose control.
(2) blood plasma hormone levels don't usually change much with aging, though there are some exceptions
(3) a single hormone may act on different tissues and have different actions in different tissues or cell types. It is therefore possible that one cell/tissue type may have an altered response to a given hormone, while the responses in other cell/tissue types are well preserved.
(4) Both secretory and clearance rates often decrease simultaneously with aging, so the net effect is a maintenance of hormone level. If there is a mismatch in the decline, there can be alterations in blood levels
(5) On a target tissue or cell, the number or affinity of the receptors for a given hormone may change. Even if blood levels are maintained, the action of the hormone may be depressed if receptor number is decreased.
changes that can occur in endocrine glands with aging:
(1) atrophy/cell loss
(2) vascular changes
(4) sometimes tumors
Hormones released by the "Hypothalamic-Pituitary-Adrenal Axis"
mediate the body's response to stress (environmental, internal physiological conditions like blood sugar, and also psycho-social) it also interacts with, and affects, the immune system.
life and responding to stress
the ability to respond appropriately to stress is essential for life.
typicla stress response is represented by:
alarm rxn --(neural endocrine response)--> enhanced adaptive capacity --(prolongation)--> exhaustion
unable to maintain homeostasis
if homeostatic mechanisms are sufficient...
a state of enhanced adaptivie capacity is attained
when is a state of exhaustion reached?
if the stressor is too intense, prolonged, or homeostatic mechanisms are impaired.
lies above the kidneys and secretes several hormones:
(1) epinephrine (catecholamine)
(2) norepinephrine (catecholamine)
(3) cortisol (glucocorticoid)
(4) aldosterone (mineralocorticoid)
(5) androgens (sex hormones)
catecholamines are reduced by the..
glucocorticoids, mineralacorticoids, and sex hormones are released from..
various layers of the cortex
region of the adrenal that is considered a sympathetic ganglion, is a component of the sympathetic nervous system, and is involved in the fight/flight/fright response
adrenal medulla, when stimulated by the sympathetic nervous system (SNS)..
releases epinephrine and norepinephrine
effect of epinephrine and norepinephrine
they act on many tissues and cause an increase in blood pressure, heart rate and contractility, and respiration, mobilize liver glycogen and fat cell free fatty acids, inhibit gastrointestinal function, widen the pupils, and accommodate to far vision, though they are not essential for life, but it does facilitate the response to stress
adrenal medulla is an extension of:
the sympathetic nervous system
what does the sympathetic nervous system release?
the catecholaimes, epinephrine and norepinephrine.
adrenal medulla with aging:
(1) at rest, plasma epinephrine and norephinephrine levels are variable; they can be hi, low, and unchanged among the elderly population.
(2) in response to stress, there is an increase in epinephrine, while norepinephrine tends to be exaggerated and will return to rest levels at a slower rate, so elderly people don't respond well ot stress.
cause of high catecholamines among the elderly
it is unknown whether high catecholamines in the elderly is due to increased release or decreased clearance
adrenal cortex, with aging:
(2) nodules (adenomas)
the adrenal cortex is very susceptive to these
major category of hormones released from the adrenal cortex:
glucocorticoids and stress
stress is sensed by the limbic system, leads to activation of the hypothalamus and the release of corticotrophin releasing hormone (CRH). CRH causes release of adrenocorticotropic hormone (ACTH) from the pituitary gland. ACTH is released in the blood and causes the release of cortisol and DHEA (androgens) from the adrenal cortex
actions of cortisol:
metabolic action of cortisol
cortisol increases amino acid uptake and gluconeogenesis by the liver, decreases amino acid uptake and protein synthesis in muscle, inhibits somatic growth, and mobilizes lipids
anti-inflammatory action of cortisol
it inhibits leukocytes, lymphocytes, and antibody production
excitatory action of cortisol
it excites the central nervous system, mainly the hippocampus, which has many receptors for cortisol
prolonged elevation of cortisol causes...
tissue breakdown, and is toxic to hippocampal cells. Hippocampal cells also inhibit the release of CRH, so loss of hippocampal cells can lead to a further increase in cortisol levels.
effects of chronically increased cortisol are similar to...
changes seen with aging, and they are the basis of the "glucocorticoid cascade hypothesis of aging"
unchanged aspects of the adrenal cortex with aging:
(1) plasma cortisol/ACTH levels
(2) circadian levels or ACTH/cortisol
(3) response to CRH injection
(4) number and affinity of glucocorticoid receptors in tissues
cortisol and aging
there is some evidence that the secretion and clearance of cortisol decreases with aging, and results in the maintenance of normal plasma levels.
normal acute physiological response to stress:
(1) increased sympathetic output (increases vigilance, arousal)
(2) decreased parasympathetic output
(3) decreased insulin secretion
(4) increased glucocorticoid secretion from adrenal cortex
(5) increased blood norepinephrine and epinephrine (released from sympathetic nerves and adrenal medulla)
(6) increased glucagons (released from pancreas)
(7) release of growth hormone
all of these responses act to mobilize energy
what happens when the response to stress does not restore homeostasis/stress is chronic?
(1) adaptation to stress is incomplete
(2) there are symptoms of poor health, which include:
-type II diabetes
-ulcers, colitis, diarrhea
-inhibition of growth (childhood)
-osteoporosis (old age)
-decreased LHRH and testosterone
physiological changes similar to those seen in aging that occur in young animals that are exposed to chronic severe stress:
(1) decreased thymus size and impaired immune function
(2) exaggerated hormonal response to acute stress
(3) adrenal hypertrophy
(4) vascular inflammation
parameters associated with a decrease in homeostatic ability in humans:
(1) elevated blood pressure (index of cardiovascular function)
(2) increased waist-hip ratio (index of long-term metabolic function and lipid deposition; chronic increase in cortisol can lead to fat accumulation in the abdominal region)
(3) increased total cholesterol and decreased HDL cholesterol (index of vascular disease risk)
(4) glycosylated hemoglobin (index of chronically elevated glucose and impaired glucose metabolism)
(5) decreased DHEA (index of Hypothal.-Pit-Adrenal axis function)
(6) increased 2-hour urinary cortisol, epinephrine, norepiinephrine (index of H-P-A Axis activity)
when all of these factors are outside of the desired range, they endanger health and shorten life
what else supports the neuro-endocrine-immune theories of aging?
the loss of hippocampal cells and impaired immune function with chronic stress
newer theories on neuro-endocrine-immune aging
propose that there is not a generalized, random loss of neuro-endocrine-immune function, ut instead there are pacemaker cells in the brain that control the aging process through the neuroendocrine and immune systems.
successful aging involves...
coping with stress
characteristics of animals raised in a nurturing environment:
(1) lower levels of stress hormones in response to acute stress
(2) faster recovery after stress
(3) enhanced sensitivity of glucocorticoid feedback
early learned stress management carries throughout life, and a lifetime of stress management ins considered an important component of successful aging
Two parts of the pituitary gland:
anterior pituitary and posterior pituitary
these two regions release different hormones
located in the brain and is often considered a master gland because it controls the activity of other glands, like the adrenal cortex, thyroid, gonads, and other target tissues. The pituitary gland is closely linked with the hypothalamus
composed of secretory cells
contains cells that are extensions of neurons from the hypothalamus
structure of pituitary gland with aging
its structures tends to be generally well-preserved, except for the cells that release gonadotropes and growth hormone
GH (growth hormone)
it is a growth hormone during development, but is considered a stress hormone in adults, because its release is stimulated by stress.
stress causes the release of...
GRH from the hypothalamus, which causes the release of GH and GIH (Growth hormone inhibiting hormone) from the pituitary
this hormone inhibits the release of GRH (negative feedback).
GH can act dirrectly on..
tissues, and it also causes the release of IGF1 (Insulin-like growth factor 1) from tissues. GH and IGF1 have similar actions on target tissues.
Actions of GH and IGF1 before adulthood:
they allow for growth, and the protein anabolism of tissues. Without them, an individual with have dwarfism and/or mental retardation
actions of GH and IGF1 in adulthood:
they increase lean mass and BMR by:
-decreasing blood cholesterol
-increasing liver glucose production
-have an anti-insulin effect in muscle, causing there to be
less glucose uptake)
- they stimulate pancreatic beta cells, which, if exhausted,
can result in diabetes
GH with aging
GH response to stress is blunted. The GH peak during hte night is also blunted; this is because it occurs during stages III and IV sleep, which are shortened with aging. GH is reduced with obesity, so the prevalence of obesity in the elderly might be a factor in the decreased levels of GH.
The decreased GH surge with aging is often associated with...
decreased bone synthesis, decreased lean body mass, decreased bone formation, and an increase in adiposity.
Why has GH replacement been tried as a counter-measure to the previously listed effects of decreased GH surge in aging...
because the effects of GH would oppose these changes.
long-term (6 mo.) effects of GH supplementation...
increases muscle and bone mass, and decreases fat mass in elderly men and women. This effect is small, however, and requires constant treatment/supplementation with GH.
role of decreased GH in aging..
because GH replacement has no proven effects on lifespan, its role in aging is unclear.
side effects of GH replacement
joint swelling and pain, cardiac arthymmias, and insulin resistance.
animal models for growth hormone is suppressed
snell dwarf mice, Pit1 mice
human models for suppressed growth hormone
people with laron syndrome
these models have...
longer lives, so the drop in growth hormone with age may actually be protective.
located at the base of the neck and secretes thyroid hormones, T3 and T4.
the thyroid hormone that is more abundant and stable in the blood. Converted into T3 within cells
the active thyroid hormone
T3 and T4 are released in response to..
thyroid sitmulating horone (TSH), which is released from the anterior pituitary
what do T# and T4 do, when they are at sufficient levels?
suppress the release of TSH and TRH
function of thyroid hormones during development
they are necessary for whole body growth, organ growth, and the maturation of the central nervous system
function of thyroid hormones in adults
they are essential for metabolic function (regulates tissue oxygen consumption), and this controls BMR and body temperature
are thyroid hormones essential for life?
no, but people are negatively affected when thyroid hormones do not function properly, or are not present
children without thyroid hormones
can have dwarfism and/or mental retardation
adults without thyroid hormones
have poor resistance to cold, and have mental and pysical lethargy, as well as decreased BMR
release of thyroid stimulating hormone (TSH)
its release from the hypothalamus is chronic under normal conditions, but it can be up-regulated in infants in response to cold, and it can be down-regulated in adults in response to stress
Types of changes in the thyroid with aging:
(3) Changes in BMR
morphological changes in the thyroid with aging:
(1) distention of follicles
(2) flattening of epithelial cells
(3) decreased mitosis
(4) increased fibrosis
(5) atherosclerotic changes in gland
secretory changes in the thyroid with aging:
(1) decreased T3 levels (low normal, so it is not always pathological)
(2) decreased secretion and clearance of T4 (normal blood levels)
(3) decreased conversion of T4 to T3, so there will be less of the active thyroid hormone T3
(4) T3 nuclear receptors don't upregulate
(5) increased TSH levels by about 10%
Changes in BMR with aging:
(1) there is a progressive decline in BMR with aging
(2) this may be partly due to decreased T3 levels
(3) it may also be due to increased adipose tissue, which is less metabolically active
Injections of high doses of T4 in young animals:
causes an increased appetite and growth
injections of high doses of T4 in adult animals
causes muscle wasting and catabolism
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