Physiology of Aging

1. Physiology of Aging J.M. Cairo, Ph.D. jcairo@lsuhsc.edu 504-568-4246

2. Demographics • Life expectancy has nearly doubled since the beginning of the 20th century • It is estimated that by the year 2020, 47% of the population will be >50 years of age.

3. Demographics • Population over 65 is fastest growing age group in the US: >85 years is the fastest growing segment of this group • People over 65 years constitute 14% of the total US population and will account for 20% of the total US population over the next 50 years • ♂:♀ = 39:100; by the age of 85, this ratio shrinks progressively thereafter

5. Demographics • 1 of 4 patients undergoing surgery >65 years • 50% of patients over 65 years have an operation in the remainder of their lives • 12% of patients >65 years use 65% of the total medical resources each year

6. 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

7. 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

8. 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

9. Aging and the Respiratory System • Mechanics of Breathing • Pulmonary Circulation • Gas Exchange • Control of Breathing

10. 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

11. 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

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

13. 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.

14. 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.

15. 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.

16. 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

18. 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

19. Aging and the Cardiovascular System • Heart • Blood Vessels • Central vessels (e.g., aorta) • Peripheral vessels

20. Aging and the Heart • There is a linear loss of myocardial cells beginning during infancy (~38 million per year) • The remaining myocardial cells hypertrophy (ventricular wall thickness is therefore preserved over time) • Increase in fibrous connective tissue matrix

21. Aging and the Heart • Systolic function is relatively preserved • Velocity of myocardial shortening decreases but the duration of contraction is prolonged

22. Aging and the Heart • Delayed diastolic relaxation coupled with increased myocardial stiffness leads to increased venous filling pressures • The heart’s inotropic and chronotropic responses, as well as, the vascular responsiveness to catecholamines are reduced • sympathetic nervous system stimulation is apparently related to receptor function

23. Aging and the Vasculature • Changes in the systemic arterial wall occur predominantly in the medial layer • The changes that occur with aging involve elastin fibers undergoing progressive disorientation, fragmentation, and degeneration, with subsequent collagen deposition, calcification, and cystic degeneration.

24. Aging and the Vasculature • Central elastic vessels dilate and become more tortuous. The increase in stiffness of the aorta and central elastic arteries is not found in the peripheral arteries. • This results in a doubling of the pulse wave velocity in the aorta, a quadrupling of the descending aorta impedance, and a progressive rise in systolic pressure

25. Hemodynamic Effects • Resting cardiac output, stroke volume, and peak aortic flow may change little with age • Systemic Blood Pressure • Systolic pressure rises 6.0-7.0 mmHg per decade • Diastolic pressure remains relatively constant (it may actually fall with increases in systolic pressure)

26. Hemodynamic Effects • The cardiovascular response to exercise declines progressively • Maximal HR, SV, CO, Ejection Fraction, and VO2 decrease • End-systolic and end-diastolic volumes increase • The age-related diastolic dysfunction makes the elderly more susceptible to the effects of tachycardia

27. Cardiovascular Response to Exercise: Young versus Older Subjects

28. Effect of Conditioning on Heart Rate Response

30. Perioperative Implications • Small decreases of venous filling from narcotics, diuretics, volume depletion, and positive pressure ventilation can have profoundly negative effects on stroke volume and cardiac output. • Inhalation anesthetics exaggerate the negative inotropic and chronotropic effects of calcium channel blockers and beta-adrenergic blockers

31. Perioperative Implications • Fluid overloads may precipitate heart failure and pulmonary edema in the elderly more easily than in young subjects • Perioperative hypotension is more frequent and severe in the elderly than in the young

32. Renal System • Although kidney function declines with age, it does not cause any major problems unless blood flow is severely restricted due to heart problems

33. Renal SystemClinical Implications • The capacity of the bladder does decline significantly (it may retain 100 mL of urine thus diminishing its overall capacity. • The frequency and urgency may be frustrating because the urgency to urinate does not occur until the bladder is near capacity • Incontinence affects about 15% of patients over 65 years and 60% of all patients institutionalized over the age of 65 years • Bladder problems may result from weakness of the bladder outlet or distension of the bladder • In males, prostate problems may increase frequency or loss of control

34. Digestive System • Eating habits may change due to changes in ability to taste food, loss of teeth due to periodontal diseases, or the presence of dentures • There is an decrease in digestive enzymes and the beginning of atrophy of glands in the stomach causing food to move slower through the digestive tract. • Increased incidence of diverticulitis and rupture

35. Age-Related Neurological and Psychological Changes • Decline in receptors, fewer afferent conduction pathways, fewer brain cells (i.e., decreased mass and increase in CSF) and connections and slower corticospinal transmission • Baroreceptor responsiveness, postural response and vasoconstrictor response are all impaired in rate and magnitude • Sensory thresholds for stimuli are blunted (vision, hearing, taste, pain, temperature)

36. Age-Related Neurological and Psychological Changes • Psychomotor response-reaction time • Problem-solving • Memory • Cognitive impairment • Delirium • Can results from a variety of causes, including hypoxia, electrolyte disturbances, hypotension, and pharmacologic toxicity • Associated with increased perioperative mortality • Dementia • Can result from undernutrition, acute situational stress, family history of mental illness, and personal history of substance abuse • Depression

37. Sensory Issues • Vision • Begins to change in mid 40’s in five major ways: • Lens thickens • Lens tends to harden and is more sensitive to glare • Lens becomes more yellow which changes color perception • Pupil becomes smaller letting in less light • Muscles controlling opening and closing respond slower making it harder to perceive quick-moving objects • Hearing • One in three people over 65 years have some degree of hearing impairment (i.e., conductive versus nerve loss).

38. Sensory Issues • Touch • As the skin thins and loses nerve cells, it is more difficult to distinguish changes in temperature. At the age of 25 years, a person can perceive a 1 degree drop in temperature by touch; at age 65 years, it would take a 9 degree change to be equivalent. • Taste • Loss of taste alters eating habits. A 30 year old has about 245 taste buds on each papilla on the tongue; the number begins to decrease at age 50 and will progress to a loss of about 65% of those taste buds at the age of 80 years. Of the four basic taste sensations, sweet taste buds diminish the most, sour the least, with bitter and salty fitting in the middle. • Smell • Odors must be 2 to 12 times more intense for a 70 year old than a 25-35 year old. 25% of people between 65 and 80 have major smell dysfunctions and after 80 years it increases to 50%.

39. Theories of Aging • Metabolic Damage • Free-Radicals • Glycation

40. Free Radicals and Aging

41. 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