Lectures 14-26

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Midterm 2 Exam ReviewLectures 14-26

Neurons that can proliferate into adulthood include:

• Neuroblasts in the subventricular zone (SVZ) and subgranular layer which migrate towards the olfactory bulb and hippocampus respectively

• Dormant Neuroprogentior cells • Neuroglia

The rate of degeneration far exceeds the ability of these cells to compensate for neuronal loss

Research seeking to activate/increase proliferation of these cells to regenerate lost brain tissue (neural stem cells) in neurodegenerative diseases

Neurons:

Axons- transmit signal, only one per cell

Dendrites- receive signal, numerous projections per cell

Glial Cells:

Astrocyte- structural/nutritional support for neurons

Oligodendrocyte- sheath axons, allow for faster action potential transmittance- protective roles

Microglia- neuronal immune cells

• In normal aging, moderate neuronal loss occurs in the:

Locus Ceruleus: nucleus in the brain stem (inferior to the cerebellum in the caudal midbrain/rostral pons) apparently responsible for the physiological reactions involved in stress and panic. This nucleus is the major location of neurons that release norepinephrine throughout the brain. Implicated in wide ranging disorders: depression, panic, anxiety disorders, Posttraumatic stress disorder

Substantia Nigra: A dark band of gray matter deep within the brain where cells manufacture the neurotransmitter dopamine for movement control. Degeneration of cells in this region may lead to a neurologic movement disorder such as Parkinson's disease

Nucleus basalis of meynert:Lateral part of the tuber cinereum that provides most of the acetylcholine to the cerebral cortex. Decrease in production seen in Alzheimer’s disease and Lewy Body dimentia.

Hippocampus: The part of the brain that assists in storing memory by sorting and sending new bits of information to be stored in appropriate sections of your brain and recalling them when necessary

Major functional deficits/ pathologies involve:

Motility (e.g. Parkinson’s Disease)

Senses and communication

Cognition (e.g. dementias)

Affect and mood (e.g. depression)

Blood circulation (stroke, multi-infarct dementia)

Pathological and Cellular Pathological and Cellular Changes with Normal AgingChanges with Normal Aging

Pathological and Cellular Pathological and Cellular Changes with Normal AgingChanges with Normal Aging

• Increased intracellular deposits of lipofuscinIncreased intracellular deposits of lipofuscin• Intracellular formation of PHFsIntracellular formation of PHFs• Accumulation of amyloid deposits in the neuritic Accumulation of amyloid deposits in the neuritic

plaques and surrounding the cerebral blood vesselsplaques and surrounding the cerebral blood vessels• Accumulation of Lewy bodiesAccumulation of Lewy bodies• Cell death (apoptosis, necrosis)Cell death (apoptosis, necrosis)

• Increased intracellular deposits of lipofuscinIncreased intracellular deposits of lipofuscin• Intracellular formation of PHFsIntracellular formation of PHFs• Accumulation of amyloid deposits in the neuritic Accumulation of amyloid deposits in the neuritic

plaques and surrounding the cerebral blood vesselsplaques and surrounding the cerebral blood vessels• Accumulation of Lewy bodiesAccumulation of Lewy bodies• Cell death (apoptosis, necrosis)Cell death (apoptosis, necrosis)

Key terms:

Lipofuscin: Lipofuscin are brown pigment granules representing lipid-containing residues of lysosomal digestion and considered one of the aging or "wear and tear" pigments; found in the liver, kidney, heart muscle, adrenals, nerve cells, and ganglion cells.

PHF: Paired helical filaments (PHF) are abnormal, approximately 20-25-nm wide periodically twisted

filaments, which accumulate in Alzheimer's disease (AD) brain and other neurodegenerative disorders, including corticobasal degeneration (CBD). PHF are primarily composed of highly phosphorylated tau

protein, proteins that interact with and stabilize microtubules, promote tubulin assembly (MAP).

Amyloid:insoluble fibrous protein aggregations sharing specific structural traits (cross-beta quaternary structure) commonly found in Alzheimer’s disease. Main constituent of amyloid plaques are Abeta (Amyloid beta)proteins, formed after cleavage of amyloid prescursor protein (APP). Autosomal-dominant mutations can cause early onset AD.

Lewy Body: abnormal aggregates of protein that develop inside nerve cells. A Lewy body is composed of the protein alpha-synuclein associated with other proteins such as ubiquitin, neurofilament protein, and alpha B crystallin. Linked to Parkinson’s disease.

Short video on Parkinson’s Disease and GDNF therapy:http://www.youtube.com/watch?v=gnDHMveS9_M

Parkinson’s Disease:

Parkinson's disease (also known as Parkinson disease or PD) is a degenerative disorder of the central nervous system that often impairs the sufferer's motor skills and speech

Symptoms:

•Tremor

•Rigidity

•Bradykinesia/akinesia: respectively, slowness or absence of movement

•Postural Instability

•Gait abnormalities

•Fatigue

•Soft speech/Drooling

•Results from the loss of pigmented dopamine-secreting (dopaminergic) cells

•Neurons project to the striatum and their loss leads to alterations in the activity of the neural circuits within the basal ganglia that regulate movement, in essence an inhibition of the direct pathway and excitation of the indirect pathway.

•The direct pathway facilitates movement and the indirect pathway inhibits movement, thus the loss of these cells leads to a hypokinetic movement disorder.

•The lack of dopamine results in increased inhibition of the ventral lateral nucleus of the thalamus, which sends excitatory projections to the motor cortex, thus leading to hypokinesia.

•The mechanism by which the brain cells in Parkinson's are lost may consist of an abnormal accumulation of the protein alpha-synuclein bound to ubiquitin in the damaged cells. The alpha-synuclein-ubiquitin complex cannot be directed to the proteosome. This protein accumulation forms proteinaceous cytoplasmic inclusions called Lewy bodies.

Alzheimer's disease (AD), also known simply as Alzheimer's, is a neurodegenerative disease characterized by progressive cognitive deterioration together with declining activities of daily living and neuropsychiatric symptoms or behavioral changes. It is the most common type of dementia. The ultimate cause of the disease is unknown

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Anatomo-Histology

Brain atrophy, flattening of gyri,widening of sulci,

& cerebral ventricles

Loss of cholinergic neurons, in nucleus of Meynert, hippocampus & association cortices

Loss of adrenergic neurons, in locus

ceruleus

Denudation of neurons, stripping of dendrites,

damage to axons

Increased microglia

Pathology

Accumulation of cell inclusions: lipofuscin, Hirano and Lewy bodies, altered cytoskeletal

Tau proteins, ubiquitin

Neurofibrillary tangles, neuritic plaques with

amyloid,

Perivascular amyloid, distributed throughout

the brain, but especially in frontal,

prefrontal lobes, Hippocampus,

association cortices

Metabolism

Decreased oxidative metabolism, slower enzyme activity (Ch.

7)

Free-radical accumulation (Ch. 5)

Impaired iron homeostasis (Ch. 7) Other minerals, zinc,

aluminum

Reduced level/metabolism/

activity of neurotransmitters

Increased amyloid peptide with

accumulation of amyloid proteins

Increased prion protein

Altered immune response

Dementia (from the Latin de-mens, without mind) is a clinical syndrome that refers to a global deterioration of intellectual and cognitive functions characterized by a defect of all five major mental functions:

• Orientation• Memory• Intellect• Judgment• AffectBut with persistence of a clear consciousness.

TABLE 8-8 Type s of Cognitive Impairment in the Elderly to be Differentiated from Alzheimer’s Disease

• Delirium: an acute or subacute alter ation of mental status

characterizedby clouding of conscious ,ness fluctuation of symptoms and improvement of ment al function after removal of

( cause reversibledementia).

• Depression: a specific psychiatric entity that can precede or be associated withdem , entia and th at can be differentiall y

diagnosed and treat .ed

• Benign Senescent Forgetfulness: not progressive and not of sufficient severity to interfere with every .day functions

• Paranoid States and Psychoses: psychiatric diseases

• Amnesic Syndrome: short- term memorylosses without delirium or

dementi .a

TABLE 8-9 Characteristics of Multi-Infarct Dementia

History of abrupt onset or stepwise deterioration History of transient ischemic attack or stroke Presence of hypertension or arrhythmia Presence of any neurologic focal symptoms or signs

FAST ---------------------> SLOW

Neural recruitment

Information processing speed

LESS ---------------------> MORE

Memory Load2 6 2 6

500

750

1000

1250

1500

Young Old

Reaction Time (msec)

FASTEST SLOWEST

YOUNG

OLD

ApoptosisProgrammed Cell Death - executed in such a way as to

safely dispose of cell corpses and fragments.

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•Evolutionarily conserved

•Occurs in all multicellular animals studies (plants too!)

•Stages and genes conserved from nematodes (worms)and flies to mice and humans

•Important in embryogenesis

•Selection/ Eliminates non-functional cells

•Immunity-eliminates dangerous cells

•Organ size - eliminates excess cells

•Tissue remodeling - mammary gland/ prostate

APOPTOSIS: Role in Disease

TOO MUCH: Tissue atrophy

TOO LITTLE: Hyperplasia

NeurodegenerationThin skin

etc

CancerAthersclerosis

etc

APOPTOSIS: Role in DiseaseAGING

Aging --> both too much and too little apoptosis(evidence for both)

Too much (accumulated oxidative damage?)---> tissue degeneration

Too little (defective sensors, signals?---> dysfunctional cells accumulatehyperplasia (precancerous lesions)

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Average refractive error becomes more hyperopic with age. A refractive error means that the shape of your eye does not bend light correctly, resulting in a blurred image

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•The lens becomes more yellow with age and absorbs more light, accelerating after the age of 60

•Increased lens fluorescence with age. The fluorescence of the human lens is caused by accumulation of advanced glycation end products formed by non-enzymatic glycation on lens proteins. Advanced glycation end products are important for the pathogenesis of diabetic long-term complications

•Amplitude of accommodation (AA) is a measurement of the eye ﾕ s ability to focus clearly on objects at near distances - decreases linearly with age

Visual acuity declines modestly in high contrast conditions - larger losses seen in low contrast conditions due to higher loss of rods over cones with age

Rods - type of specialized photoreceptors in the retina that provide peripheral vision and the ability to see objects in dim light, used extensively for night vision. The rods lie outside the fovea in the more peripheral parts of the retina. Most nocturnal animals rely solely on the use of rods for their vision as this allows them to perceive as much as possible visual information in conditions of low illumination

Cones - cone-shaped light-sensitive cells in the retina particularly in the macula area; cone function predominates in daylight with a small pupil allowing one to make out details and shapes, especially colors

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Color vision changes with age are most commonly of the blue-yellow variety

Cyanopsia

Xanthopsia

Recommendations to accommodate for age-related declines in vision:

Wear appropriate optical correction

Improve contrast in critical areas

Increase ambient light levels

Avoid rapid changes in light levels

Avoid pastel or muddy colors

Functions of the CV system• Transports O2 & nutrients to the tissues

& returns C02 to the lungs and other products of metabolism to the kidney

• Regulates body temperature

• Distributes hormones and other agents that regulate cell function

Components:

Heart

Pump that circulates the blood throughout the body

Vascular System

Transports blood to the body tissues

Central Nervous System (CNS)

Particularly the centers in the medulla that regulate the function of the heart and blood vessels

Key words:

Arteriosclerosis: a chronic disease characterized by abnormal thickening and hardening of the arterial walls with a resultant loss of elasticity

Atherosclerosis: A form of arteriosclerosis characterized by the deposition of atheromatous plaques containing cholesterol and lipids on the innermost layer of the walls of large and medium-sized arteries.

Atherosclerosis can cause:Gangrene-a death of body tissue that usually occurs when there has been

an interruption of blood supply, followed by bacterial invasionAneurysm-Weakness or injury to the wall of a blood vessel causing

dilatation or ballooning and, in severe cases, threatening the integrity of the circulatory system resulting in hemorrhage or stroke. A weakened point of an artery, vein or the heart.

Stroke-Also called a "brain attack" and happens when brain cells die because of inadequate blood flow. 20% of cases are a hemorrhage in the brain caused by a rupture or leakage from a blood vessel. 80% of cases are also know as a "schemic stroke", or the formation of a blood clot in a vessel supplying blood to the brain

Myocardial infarction-destruction of heart tissue resulting from obstruction of the blood supply to the heart muscle

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Gangrene of the fingers and toes

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Aneurysm - notice ballooning of the blood vessel

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Stroke

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Theories of Atherosclerosis:

-Lipid accumulation

-Myoclonal (muscle contraction irregularities)

-Thrombogenic (blood clots)

-Inflammation

-ROS/Free Radicals

Table 16-11 Major Risk Factors inCoronary Heart Disease

AgeGenetic predispostion

HypertensionDiabetes mellitus

HypercholesterolemiaCigarette smoking

Also:Obesity

Poor physical fitness and lack of exercisePersonality type (?)

Key terms:

Triglycerides - The storage form of fat consisting of three fatty acids and glycerol

Cholesterol - Cholesterol is a sterol (a combination steroid and alcohol) and a lipid found in the cell membranes of all body tissues, and transported in the blood plasma of all animals

Lipids - Lipids are a class of hydrocarbon-containing organic compounds

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Chylomicron - large lipoprotein particles (having a diameter of 75 to 1,200nm) that are created by the absorptive cells of the small intestine. Chylomicrons transport exogenous lipids to liver, adipose, cardiac and skeletal tissue where they are broken down by lipoprotein lipase.

Low density lipoprotein - a class of lipoprotein particles that varies in size (18-25 nm in diameter) and contents (while carrying fatty acid molecules in blood and around the body). The LDL contains the apolipoproteins B-100 and Apo E.It is commonly referred to as bad cholesterol as high LDL levels can lead to cardiovascular disease.

High density lipoprotein-class of lipoproteins, varying somewhat in their size (8-11 nm in diameter), that carry cholesterol from the body's tissues to the liver.]It is hypothesised that HDL can remove cholesterol from atheroma within arteries, and transport it back to the liver for excretion or re-utilization; the main reason why HDL-bound cholesterol is sometimes called "good cholesterol", or HDL-C. A high level of HDL-C seems to protect against cardiovascular diseases, and low HDL

cholesterol levels [less than 40 mg/dL] increase the risk for heart disease. Apolipoprotein-ipid-binding proteins which are the constituents of the plasma

lipoproteins. The amphipathic (detergent-like) properties of apolipoproteins solubilize the hydrophobic lipid constituents of lipoproteins, but apolipoproteins also serve as enzyme co-factors, receptor ligands, and lipid transfer carriers that regulate the intravascular metabolism of lipoproteins and their ultimate tissue uptake.

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Key components involved:Lipoprotein lipase (LPL) -enzyme which hydrolyzes lipids in lipoproteins, like those found in chylomicrons and very low density lipoproteins (VLDL), into three fatty acids and one glycerol molecule.

Lecithin cholesterol acyltransferase (LCAT)- enzyme which converts free cholesterol into cholesteryl ester (a more hydrophobic form of cholesterol) which is then sequestered into the core of a lipoprotein particle

eventually making the newly synthesized HDL spherical. LDL receptor-mosaic protein that mediates the endocytosis of cholesterol-rich LDL. It is a cell-surface receptor that recognises the apoprotein B100 which is embedded in the phospholipid outer layer of LDL particles.

ABCA1 transporter- Essential for moving excess intracellular cholesterol and phospholipid to the plasma membrane. Acts as a flipase, flipping cholesterol and phospholipid from inner leaflet of plasma membrane to outer leaflet. Necessary for removing excess cholesterol from foam cells and preventing early steps in atherosclerosis.

Scavenger receptor A1 (SR-A1) - The scavenger receptor recognizes modified and/or oxidized LDL and internalizes the modified LDL.

Key pharmacological therapies:

Statins (atorvastatin, etc.) - target the liver, inhibits cholesterol biosynthesis, increases LDL receptors

Bile Acid Sequestrants (colestipol, etc.)-bind and remove bile in intestine, increases cholesterol conversion to bile, increases LDL clearance, lowers plasma cholesterolTriglyceride Reducers (gemfibrozil, etc.)- Reduces synthesis of VLDL in liver, increases catabolism of VLDL, lowers plasma TG, increases HDL

Cholesterol Absorption Inhibitor (ezetimibe)- Blocks uptake of dietary cholesterol in small intestine, inhibits ABC transporter receptors on surface of intestinal absorptive cells, lowers plasma cholesterol

Reverse Cholesterol TransportDelivery of peripheral tissue cholesterol to the liver for catabolism

Requires HDL, apoA-I and LCAT

Peripheral Cell UC HDL

HDLCE

HDLUC

ABCA1

LiverVLDLor LDL apoB LDLr

SR-B1

UC

PL

CE

TG

diffusion

LCAT

LCAT

CE

CE

apoA-I

UC = unesterified cholesterolCE = esterified cholesterolPL = phospholipidLDLr = LDL receptor

NascentHDL

Bile to gut

Macrophage/ Foam cell

Chol

Bile acids

HDL Protective RoleFitting the pieces together

oxLDL = oxidized LDLUC = unesterified cholesterol

ABCA1apoA-I

Endothelialcells

HDL

HDL

UC

PL

UC

Nascent HDL

HDL + UC

Macrophage foam cell

oxLDL

Monocyte

Arterywall

Exercise

VO2 Max can be maintained at high levels with age with prolonged exercise

Decreases morbidity, offers protection against developing CV diseases

Decreases mortality, offers protection against dying from CV diseases

Helps to control age-related increases in body fat

Reduces the occurrence of type II diabetes

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Exercise:

• Increases strength

• Increases prevalence of fast and slow twitch muscles

• Increases bone density

• Improves coordination, greater prevention of falls and injuries

• Increases in mitochondrial mass

• Increased expression of antioxidant enzymes

• Helps control age-related decreases in lean muscle mass• Improves mood

• Experimentally found to increase expression of neurotrophic factors (BDNF) in the mouse hippocampus

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Key termsSatellite cells - found in the mature muscle around the muscle fibres,

and differentiate from myoblasts. These cells are involved in the normal growth of muscle, as well as regeneration following injury or disease

Sarcopenia - degenerative loss of muscular strength and mass with age- Loss fastest in fast-twitch fibers- Due to inactivity, decreased protein synthesis, and neural, hormonal, and nutritional factors

Myoplasticity -ability of muscle to alter the quantity and type of its protein in response to stimulation. Physical activity leads to an increase in cross-sectional area and increase in muscular mass with changes in myosin type. Myoplasticity may involve change in amount of protein, change in type of protein, and combination of both.

-RESISTANCE training: increases amount of contractile proteins permitting increasing efforts.-ENDURANCE training: increases the velocity of contraction, increases the number of mitochondria, and increases the capacity to oxidize substrate

Physiological Changes with AgeParameter 20 years 60 years

VO2 Max (mL x kg x min) 39 29

Maximum Heart Rate 194 162

Resting Heart Rate 63 62

Max. Cardiac Output (L x min)

22 16

EJECTION FRACTION 70-80% 50-55%

Resting BP 120/80 130/80

Total Lung Capacity (L) 6.7 6.5

Vital Capacity (L) 5.1 4.4

Residual Lung Volume (L) 1.5 2.0

Body Fat % 20.1 22.3

Hypertension: most common treatable cardiovascular change in the elderlyDefinition: values above 140/90

In young, if standing BP increases slightly but in elderly it may drop up to 20 mmHg

Hypotension: diminished baro-reflex response in the elderly. With age, cerebral blood flow but autoregulation acts in a compensatory fashion; some patients maybe affected by symptomatic orthostatic hypotension

Orthostatic hypotension: drop of 20 mmHg in the systolic and 10 or more in the diastolic BP on standing upright

The baroreflex or baroreceptor reflex is one of the body's homeostatic mechanisms for maintaining blood pressure. It provides a negative feedback loop in which an elevated blood pressure reflexively causes blood pressure to decrease; similarly, decreased blood pressure depresses the baroreflex, causing blood pressure to rise.

Cardiomyopathy: A general diagnostic term designating primary myocardial disease, often of obscure or unknown etiology- technical term for heart failure. The heart may be dilated (poor pumping power), restrictive (impaired ability of the heart to fill) and hypertrophic (enlarged heart). Generally includes any heart muscle disorder not caused by coronary artery disease, hypertension or

congenital valvular or pericardial diseases. Hypertrophic cardiomyopathy common cause of sudden death due to severe arrythmia in old and young

Syncope: Light-headedness or fainting caused by insufficient blood supply to the brain (cerebral isechemia)

Can be caused by orthostatic hypotension

Vasovagal reflex:When we sit or stand, blood settles in the legs and abdomen. As a result, less blood returns to the heart. The blood vessels leaving the heart have detectors in them called baroreceptors that detect a decrease in blood pressure. The baroreceptors send a message to the brain, which in turn sends a signal to the heart to increase the heart rate, and tighten up the blood vessels. This process occurs constantly in all of us as we adapt to changes in posture.

In vasovagal syncope, an abnormal reflex occurs that results in withdrawal of the message that speeds up the heart and tightens up the vessels, often because of an overshoot in the reflex that compensates for the fall in blood pressure ･ The resultant decrease in blood flow to the brain will result in dizziness or lightheadedness if mild, and progress to fainting or loss of consciousness if more severe ･ There are several variants of vasovagal syncope that can trigger the same reflex, including situations such as the sight of blood, injury, blood testing (needles), going to the washroom and several others that are quite uncommon

Myocardium: Cardiac muscle syncytium (multi-nucleated)

Endocardium: Internal layer of heart

Pericardium: External connective tissue layer of heart

Valves: openings between cardiac chambers (atrial ventricular) or between heart the arteries (aorta and pulmonary)

Conduction system: sinoatrial node (SA) is the pacemaker; also atrial ventricular node (AV), Bundle of His, Purkinje system

Sinoatrial Node: A specialized cluster of cells in the heart that initiates the heart beat. Known as the heart's natural pacemaker. Increased fibrous tissue in aged heart.

Atrio-Ventricular Node: tissue between the atria and the ventricles of the heart, which conducts the normal electrical impulse from the atria to the ventricles - slight increase in collagen fibers w/age

Bundle of His: Specialized muscle fibers in the wall between the ventricles that carry the electric impulse to the ventricles - fibrous tissue accumulation

Bundle Branch Block: Normally, the electrical impulse travels down both the right and left bundle branches at the same speed and the ventricles contract at the same time. If there is a block in one of the branches, it is called a bundle branch block. A bundle branch block causes one ventricle to contract just after the other ventricle

Aortic stenosis: Narrowing of the aortic valve opening, causing obstruction of blood flow into the circulation. The condition causes the heart to work harder and the muscle in the wall of the left ventricle (lower chamber) to thicken

Valvular sclerosis: fibrosis, accumulation of collagen and elastic tissue often with calcification of valves, age-related

Function of skeletal system:•Body Support•Body Movement•Storage of Calcium and other minerals:

•Storage of Calcium provides upon request Calcium to blood. •Blood Calcium is important for regulating numerous cellular activities

•Maintenance of Acid/Base balance in association with lungs and kidneys

•Regulation and phosphate and carbonate for buffers

•Storage of bone marrow

Composed of bones, tendons, joints

Key terms:

Osteoblasts: Cells responsible for laying down the protein matrix upon which calcium salts, particularly calcium phosphates, are deposited to form bone

Osteoclasts: Cells associated with bone that are responsible for the breakdown or resorption of bone. (Bone remodeling is a continuous process of resorption and formation.)

Osteocytes: star-shaped cell, is the most abundant cell found in bone. Once osteoblasts become trapped in the matrix they secrete, they become osteocytes. Actively involved in the maintenance of bony matrix.

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Parathyroid hormone: hormone that activates the bone resorption process, increasing calcium in the blood

Calcitonin: A hormone made in the thyroid gland that increases calcium deposition in bone and increases urinary calcium.

Calcitriol: The active form of vitamin D. Calcitriol is formed in the kidneys. It is used to increase calcium levels in the body in order to treat skeletal and tissue-related calcium deficiencies.

Osteoporosis

-A reduction in bone mass and deterioration bone microstructure

-Clinically recognized as bone fragility with an increased susceptibility to fracture

Osteopenia

Low bone density, leads to osteoporosis

Age-related causes

-Senescence of osteoblasts

-Increases levels of PTH

-also related to genetics, lifestyle, mechanical

usage, reproductive factors, etc.

Young normal

Elderly osteoporotic

1. The following are morphological changes that occur in the brain of healthy (non affected by CNS neurodegenerative diseases) elderly individuals, EXCEPT:

A. Intracellular accumulation of lipofuscinB. Intracellular accumulation of neurofibrillary tangles C. Intracellular accumulation of neuritic plaques

D. Dendritic and synaptic lossesE. Extracellular accumulation of neuritic plaques

4. Which of the following shows the largest age-related decline in visual function?

A. Glare sensitivity/Glare recoveryB. Flicker sensitivityC. Standard visual fieldD. High contrast acuityE. All of the above

5. Choose the answer that best describes how the lens contributes to changes in visual function with age.

A. Increased light scatter causes glare sensitivity B. Yellow pigment accumulates, affecting color perception C. Diameter decreases in size, reducing night vision D. A + B E. A + C

6. How does functional MRI measure changes in brain activity? A. Monitors local temperature B. Detects electrical activity C. Scans for changes in blood circulation D. Staining for neurotransmitter release E. All of the above

9. Localized factors contributing to atherosclerotic lesions include: A. Marginal vascularization of the arterial wall B. Relative ischemia (insufficient blood supply) C. Blood turbulence and mechanical stress D. All of the above E. None of the above

12. The endothelial cells of the intima have very important functions in maintaining the plasticity of the arterial wall and the fluidity of the blood. With aging:

A. The imbalance of vascular tone is manifested by increased vasodilation

B. Cell proliferation for repair is increased C. Maintenance of blood fluidity is disrupted D. Blood coagulation and thrombosis are increased E. C and D

20. Sarcopenia, or loss of skeletal muscle mass, may be due to all the following factors, EXCEPT:

A. Reduced physical activityB. Loss of peripheral motor nervesC. Reduced muscle protein synthesisD. Decreased number of circulating red blood cellsE. decreased mitochondrial mass

22.T/F Acetylcholine, nor-epinephrine, serotonin, and glutamate are major neurotransmitters in cerebral synapses 23.T/F Neuron loss with aging is universal (occurs in all brain areas) 24.T/F Free radicals are capable of initiating a chain reaction of oxidation events 25.T/F Endothelial derived relaxation factors (ERRFs) promote hypertension 26.T/F Good blood cholesterol is indicated by low serum HDL and high serum LDL 27.T/F Poor diet and lack of exercise is one of the leading causes of death in the U.S. 28.T/F Macrophages recognize oxidized lipids by the scavenger receptor 29.T/F Denudation is the process of neuron dendrite formation

35. (12 points) Standard visual field does NOT decline with age, however, attentive visual field DOES decline with age. Based on Dr. D’Esposito's lecture on imaging the aging brain, how might changes in brain function result in the loss of attentive visual field with age? Specifically: 1) What type of brain function decreases with age? 2) What area of the brain is affected? 3) How might this reduce attentive visual field?

36. (6 points) Sarcopenia may occur under several conditions, one being old age. a) List 3 major changes, structural or functional, that characterize the muscle (including the myoneural junction) of the elderly. 1. 2. 3. b) Disuse muscle atrophy is another type of sarcopenia that may occur at all ages. Explain what it means: Is it reversible/irreversible? Give an example of one condition that leads to disuse atrophy.