Physiology of AgingPhysiology of Aging

J.M. Cairo, Ph.D.J.M. Cairo, Ph.D.jcairo@lsuhsc.edu

504-568-4246504-568-4246

DemographicsDemographics

Life expectancy has nearly Life expectancy has nearly doubled since the beginning of doubled since the beginning of the 20the 20thth century century

It is estimated that by the year It is estimated that by the year 2020, 47% of the population 2020, 47% of the population will be >50 years of age.will be >50 years of age.

DemographicsDemographics

Population over 65 is fastest Population over 65 is fastest growing age group in the US: >85 growing age group in the US: >85 years is the fastest growing years is the fastest growing segment of this groupsegment of this group People over 65 years constitute 14% People over 65 years constitute 14%

of the total US population and will of the total US population and will account for 20% of the total US account for 20% of the total US population over the next 50 yearspopulation over the next 50 years

♂♂:♀ = 39:100; by the age of 85, this :♀ = 39:100; by the age of 85, this ratio shrinks progressively thereafterratio shrinks progressively thereafter

DemographicsDemographics

1 of 4 patients undergoing 1 of 4 patients undergoing surgery >65 yearssurgery >65 years

50% of patients over 65 years 50% of patients over 65 years have an operation in the have an operation in the remainder of their livesremainder of their lives

12% of patients >65 years use 12% of patients >65 years use 65% of the total medical 65% of the total medical resources each yearresources each year

Searching for Answers The medical literature is predominantly

composed of cross-sectional studies rather than longitudinal studies

Published studies indicated that cardiopulmonary, hepatic, renal, neurological, and immune functions are reduced in the elderly and susceptible to decompensation

Metabolism There is no consensus on the best method of

assessing nutritional status in the elderly Increased mortality in underweight people There is a progressive loss of skeletal mass, renal

mass, and liver mass with a reciprocal increase in lipid composition of the body Calcium and phosphorus metabolism are adversely

affected with age thus mineral levels in blood are maintained by drawing on the body’s resources (bones) leaving bones pitted, brittle, and porous

Metabolism 10-15% reduction in metabolic requirements

in elderly versus young Decrease in body heat production coupled

with impairment of thermoregulatory vasoconstriction

Delayed drug clearing due to reductions in hepatic and renal elimination

Aging and the Respiratory System

Mechanics of Breathing Pulmonary Circulation Gas Exchange Control of Breathing

Mechanics of Breathing

Rounding of the thorax Calcification of the costal cartilages

(Decreased thoracic compliance) Decreased space between the

spinal vertebrae and a greater degree of spinal curvature

Mechanics of Breathing

Progressive enlargement of the respiratory bronchioles and alveolar ducts

Loss of functional alveolar surface area and alveolar surface tension 15% reduction by the age of 70 years Negative effects on forced expiratory flow

Decreased respiratory muscle strength and endurance

Levitzky, MG: Pulmonary Physiology,7th Edition. New York, Lange, 2007

Pulmonary Circulation

Changes in the pulmonary circulation are difficult to separate from those attributable to the heart and circulatory system

In contrast to comparatively similar resting values with the young, older persons demonstrate significantly higher PA, PAWP, and PVR during exercise.

Gas Exchange

Gas exchange declines at 0.5%/yr Ventilation-perfusion ratios are adversely

affected by increasing age. Increased areas of high V/Q thus causing

an increase in physiological dead space from ~20% at 20 year old subject to 40% at 60 years of age.

There is also an increase in the proportion of alveoli that have a low V/Q resulting in an increase in venous admixture.

Gas Exchange

Baseline arterial oxygenation is lower with age PaO2 declines by 1 torr/yr after the age of

60 years The risk of hypoxemia and hypercarbia

is higher in patients >70 years and their respond to supplemental oxygen is reduced.

Control of Breathing

Elderly individuals have a significantly diminished response to hypoxia and hypercapnia Higher incidence of apnea and periodic

breathing with narcotics There is a markedly diminished

response for vocal cord closure thus increasing the risk of aspiration and its consequences

Implications for Clinicians

Decreased maximum breathing capacity, vital capacity, and maximal O2 uptake

Decreased mucociliary clearance and cellular and humoral lung defense mechanisms Increased risk for respiratory infections

Acute and chronic respiratory conditions can have severe consequences as a result of hypoxemia and hypercapnia

Aging and the Cardiovascular Aging and the Cardiovascular SystemSystem

HeartHeart Blood VesselsBlood Vessels

Central vessels (e.g., aorta)Central vessels (e.g., aorta) Peripheral vesselsPeripheral vessels

Aging and the HeartAging and the Heart

There is a linear loss of myocardial There is a linear loss of myocardial cells beginning during infancy (~38 cells beginning during infancy (~38 million per year)million per year)

The remaining myocardial cells The remaining myocardial cells hypertrophy (ventricular wall thickness hypertrophy (ventricular wall thickness is therefore preserved over time)is therefore preserved over time)

Increase in fibrous connective tissue Increase in fibrous connective tissue matrixmatrix

Aging and the HeartAging and the Heart

Systolic function is relatively Systolic function is relatively preservedpreserved

Velocity of myocardial shortening Velocity of myocardial shortening decreases but the duration of decreases but the duration of contraction is prolongedcontraction is prolonged

Aging and the HeartAging and the Heart

Delayed diastolic relaxation coupled Delayed diastolic relaxation coupled with increased myocardial stiffness with increased myocardial stiffness leads to increased venous filling leads to increased venous filling pressurespressures

The heart’s inotropic and chronotropic The heart’s inotropic and chronotropic responses, as well as, the vascular responses, as well as, the vascular responsiveness to catecholamines are responsiveness to catecholamines are reduced reduced sympathetic nervous system stimulation is sympathetic nervous system stimulation is

apparently related to receptor functionapparently related to receptor function

Aging and the VasculatureAging and the Vasculature

Changes in the systemic arterial wall Changes in the systemic arterial wall occur predominantly in the medial occur predominantly in the medial layerlayer The changes that occur with aging The changes that occur with aging

involve elastin fibers undergoing involve elastin fibers undergoing progressive disorientation, progressive disorientation, fragmentation, and degeneration, with fragmentation, and degeneration, with subsequent collagen deposition, subsequent collagen deposition, calcification, and cystic degeneration.calcification, and cystic degeneration.

Aging and the VasculatureAging and the Vasculature

Central elastic vessels dilate and Central elastic vessels dilate and become more tortuous. The increase in become more tortuous. The increase in stiffness of the aorta and central elastic stiffness of the aorta and central elastic arteries is not found in the peripheral arteries is not found in the peripheral arteries.arteries.

This results in a doubling of the pulse wave This results in a doubling of the pulse wave velocity in the aorta, a quadrupling of the velocity in the aorta, a quadrupling of the descending aorta impedance, and a descending aorta impedance, and a progressive rise in systolic pressure progressive rise in systolic pressure

Hemodynamic EffectsHemodynamic Effects

Resting cardiac output, stroke Resting cardiac output, stroke volume, and peak aortic flow may volume, and peak aortic flow may change little with agechange little with age

Systemic Blood PressureSystemic Blood Pressure Systolic pressure rises 6.0-7.0 mmHg per Systolic pressure rises 6.0-7.0 mmHg per

decadedecade Diastolic pressure remains relatively Diastolic pressure remains relatively

constant (it may actually fall with increases constant (it may actually fall with increases in systolic pressure) in systolic pressure)

Hemodynamic EffectsHemodynamic Effects

The cardiovascular response to The cardiovascular response to exercise declines progressivelyexercise declines progressively

Maximal HR, SV, CO, Ejection Fraction, and Maximal HR, SV, CO, Ejection Fraction, and VOVO22 decrease decrease

End-systolic and end-diastolic volumes End-systolic and end-diastolic volumes increaseincrease

The age-related diastolic dysfunction makes The age-related diastolic dysfunction makes the elderly more susceptible to the effects of the elderly more susceptible to the effects of tachycardiatachycardia

Cardiovascular Response to Exercise: Young versus Older Subjects

Effect of Conditioning on Heart Rate Response

Perioperative ImplicationsPerioperative Implications

Small decreases of venous filling from Small decreases of venous filling from narcotics, diuretics, volume depletion, narcotics, diuretics, volume depletion, and positive pressure ventilation can and positive pressure ventilation can have profoundly negative effects on have profoundly negative effects on stroke volume and cardiac output.stroke volume and cardiac output.

Inhalation anesthetics exaggerate the Inhalation anesthetics exaggerate the negative inotropic and chronotropic negative inotropic and chronotropic effects of calcium channel blockers effects of calcium channel blockers and beta-adrenergic blockersand beta-adrenergic blockers

Perioperative ImplicationsPerioperative Implications

Fluid overloads may precipitate heart Fluid overloads may precipitate heart failure and pulmonary edema in the failure and pulmonary edema in the elderly more easily than in young elderly more easily than in young subjectssubjects

Perioperative hypotension is more Perioperative hypotension is more frequent and severe in the elderly frequent and severe in the elderly than in the youngthan in the young

Renal SystemRenal System

Although kidney function declines Although kidney function declines with age, it does not cause any major with age, it does not cause any major problems unless blood flow is problems unless blood flow is severely restricted due to heart severely restricted due to heart problemsproblems

Renal SystemRenal SystemClinical ImplicationsClinical Implications

The capacity of the bladder does decline The capacity of the bladder does decline significantly (it may retain 100 mL of urine thus significantly (it may retain 100 mL of urine thus diminishing its overall capacity.diminishing its overall capacity. The frequency and urgency may be frustrating because The frequency and urgency may be frustrating because

the urgency to urinate does not occur until the bladder is the urgency to urinate does not occur until the bladder is near capacitynear capacity

Incontinence affects about 15% of patients over 65 Incontinence affects about 15% of patients over 65 years and 60% of all patients institutionalized over the years and 60% of all patients institutionalized over the age of 65 yearsage of 65 years

Bladder problems may result from weakness of the Bladder problems may result from weakness of the bladder outlet or distension of the bladder bladder outlet or distension of the bladder

In males, prostate problems may increase frequency or In males, prostate problems may increase frequency or loss of controlloss of control

Digestive SystemDigestive System

Eating habits may change due to changes in Eating habits may change due to changes in ability to taste food, loss of teeth due to ability to taste food, loss of teeth due to periodontal diseases, or the presence of periodontal diseases, or the presence of denturesdentures

There is an decrease in digestive enzymes and There is an decrease in digestive enzymes and the beginning of atrophy of glands in the the beginning of atrophy of glands in the stomach causing food to move slower through stomach causing food to move slower through the digestive tract.the digestive tract.

Increased incidence of diverticulitis and ruptureIncreased incidence of diverticulitis and rupture

Age-Related Neurological Age-Related Neurological and Psychological and Psychological

ChangesChanges• Decline in receptors, fewer afferent Decline in receptors, fewer afferent

conduction pathways, fewer brain cells conduction pathways, fewer brain cells (i.e., decreased mass and increase in (i.e., decreased mass and increase in CSF) and connections and slower CSF) and connections and slower corticospinal transmissioncorticospinal transmission

• Baroreceptor responsiveness, postural Baroreceptor responsiveness, postural response and vasoconstrictor response response and vasoconstrictor response are all impaired in rate and magnitudeare all impaired in rate and magnitude

• Sensory thresholds for stimuli are Sensory thresholds for stimuli are blunted (vision, hearing, taste, pain, blunted (vision, hearing, taste, pain, temperature)temperature)

Age-Related Neurological and Age-Related Neurological and Psychological ChangesPsychological Changes

• Psychomotor response-reaction timePsychomotor response-reaction time• Problem-solvingProblem-solving

• MemoryMemory• Cognitive impairmentCognitive impairment

• DeliriumDelirium• Can results from a variety of causes, including Can results from a variety of causes, including

hypoxia, electrolyte disturbances, hypoxia, electrolyte disturbances, hypotension, and pharmacologic toxicity hypotension, and pharmacologic toxicity

• Associated with increased perioperative Associated with increased perioperative mortalitymortality

• DementiaDementia• Can result from undernutrition, acute Can result from undernutrition, acute

situational stress, family history of mental situational stress, family history of mental illness, and personal history of substance illness, and personal history of substance abuseabuse

• DepressionDepression

Sensory IssuesSensory Issues

VisionVision Begins to change in mid 40’s in five major Begins to change in mid 40’s in five major

ways: ways: Lens thickensLens thickens Lens tends to harden and is more sensitive to Lens tends to harden and is more sensitive to

glareglare Lens becomes more yellow which changes Lens becomes more yellow which changes

color perceptioncolor perception Pupil becomes smaller letting in less lightPupil becomes smaller letting in less light Muscles controlling opening and closing Muscles controlling opening and closing

respond slower making it harder to perceive respond slower making it harder to perceive quick-moving objectsquick-moving objects

HearingHearing One in three people over 65 years have some One in three people over 65 years have some

degree of hearing impairment (i.e., degree of hearing impairment (i.e., conductive versus nerve loss).conductive versus nerve loss).

Sensory IssuesSensory Issues TouchTouch

As the skin thins and loses nerve cells, it is more As the skin thins and loses nerve cells, it is more difficult to distinguish changes in temperature. At difficult to distinguish changes in temperature. At the age of 25 years, a person can perceive a 1 the age of 25 years, a person can perceive a 1 degree drop in temperature by touch; at age 65 degree drop in temperature by touch; at age 65 years, it would take a 9 degree change to be years, it would take a 9 degree change to be equivalent.equivalent.

TasteTaste Loss of taste alters eating habits. A 30 year old Loss of taste alters eating habits. A 30 year old

has about 245 taste buds on each papilla on the has about 245 taste buds on each papilla on the tongue; the number begins to decrease at age 50 tongue; the number begins to decrease at age 50 and will progress to a loss of about 65% of those and will progress to a loss of about 65% of those taste buds at the age of 80 years. Of the four taste buds at the age of 80 years. Of the four basic taste sensations, sweet taste buds diminish basic taste sensations, sweet taste buds diminish the most, sour the least, with bitter and salty the most, sour the least, with bitter and salty fitting in the middle.fitting in the middle.

SmellSmell Odors must be 2 to 12 times more intense for a 70 Odors must be 2 to 12 times more intense for a 70

year old than a 25-35 year old. 25% of people year old than a 25-35 year old. 25% of people between 65 and 80 have major smell dysfunctions between 65 and 80 have major smell dysfunctions and after 80 years it increases to 50%.and after 80 years it increases to 50%.

Theories of Aging Metabolic Damage

Free-Radicals Glycation

Free Radicals and Aging

Theories of Aging Replicative Senescence

Telomere shortening Inadequate DNA repair

Toxic and Non-Toxic Garbage Accumulation Protein cross-linking and aggregation Advanced glycation Atherosclerotic and amyloid plaques Lipofuscin Metals DDT, PCBs, etc