Myocardial collagen content increases with age.5,6 Collagen is the principal noncontractile protein occupying the cardiac interstitium.⁷ Increased myocardial collagen content renders the myocardium less compliant; therefore a decrease in myocardial compliance can adversely affect diastolic filling (through decreased distensibility and dilation) and myocardial relaxation. Consequently, the left ventricle must develop a higher filling pressure for a given increase in ventricular volume. Decreased left ventricular compliance may be evident in the older adult by the presence of an S₄ heart sound.⁸

The functional consequence of these changes could be an increase in myocardial oxygen consumption. Under normal physiological conditions, an increase in myocardial oxygen demand is met with a corresponding increase in coronary artery blood flow. However, in the presence of coronary artery disease, coronary artery blood flow can be limited because of atherosclerotic-mediated narrowing of the coronary arteries. Hence the older patient is at risk for developing myocardial ischemia and/or infarction. Clinical manifestations of myocardial ischemia include electrocardiographic (ECG) changes and chest pain. However, the sensation of chest pain may be altered in the older adult. Atypical symptoms, such as dyspnea, confusion, and failure to thrive are frequently the only symptoms associated with myocardial infarction in this high-risk population.⁹

The aging heart also undergoes a modest degree of hypertrophy that is similar to pressure overload-induced hypertrophy. Such hypertrophy entails a thickening of the left ventricular wall without appreciable changes in left ventricular cavity size.¹⁰ However, increases in left ventricular cavity size associated with aging occur only in men.⁹ The increase in left ventricular wall thickness is a result primarily of an increase in muscle cell size. In older individuals the myocardial hypertrophy may be caused by corresponding increases in aortic impedance and systemic vascular resistance.¹¹

Myocardial contractility depends on numerous factors. However, the most important determinants of myocardial contraction are the intracellular level of free calcium and the sensitivity of the contractile proteins for calcium.^11,12 Because peak contractile force in the senescent myocardium is unaltered, this suggests that neither the amount of intracellular free calcium during systole nor the sensitivity of the contractile proteins for calcium is altered. The prolonged duration of contraction (systole) is caused in part by a slowed or delayed rate of myocardial relaxation, which may be an adaptive mechanism to preserve contractile function compromised by age-related increases in afterload.^3,12

Resting (supine) heart rate decreases with age.13,14 Cinelli et al¹³ reported a decrease in the resting heart rate from 78.8 beats/min in young adults to 62.3 beats/min in older adults. Heart rate is an important determinant of cardiac output (CO), and the normal resting heart beats approximately 70 times a minute. At rest or with minimal activity, the older adult probably will not experience any untoward cardiovascular effect (i.e., a decrease in CO) with a heart rate of 62 beats/min. However, if the heart rate response is attenuated during exercise, the older person’s capacity for exercise may be limited.

Resting CO and stroke volume (SV) are not changed with advancing age. At rest, left ventricular end-diastolic volume (LVEDV, preload), end-systolic volume, and the ejection fraction are not affected by age.¹⁵ In the older human myocardium, the early diastolic filling period and isovolumic phase of myocardial relaxation are prolonged.^15–17 However, these changes, although suggestive of diastolic dysfunction, do not translate into decreases in end-diastolic volume or stroke volume.^16,17 Finally, aging is associated with a moderate increase in pulmonary artery pressure.¹⁸

Advancing age produces changes in the ECG. R-wave and S-wave amplitude significantly decrease in persons older than 49 years, whereas QT duration increases¹⁹ (Table 7-2). The incidence of asymptomatic cardiac dysrhythmias increases in older patients.²⁰ The most common dysrhythmia occurring in older individuals is the premature ventricular contraction (PVC). Carom et a1²¹ and Fleg and Kennedy²² report that 70% to 80% of all patients older than 60 years experience PVCs. Other common types of dysrhythmias are sinus node dysfunction (atrial fibrillation, atrial flutter, or paroxysmal supraventricular tachycardia) and atrioventricular conduction disturbances.^15,19,20 Because the majority of patients are asymptomatic, the use of antidysrhythmics is generally not recommended. The side effects and toxic effects of antidysrhythmics impose more of a risk, as compared with the risk of mortality or morbidity related to the dysrhythmia.^20,23 In contrast, for patients who are symptomatic and have malignant ventricular dysrhythmias (sustained ventricular tachycardia and/or fibrillation), pharmacological therapy is warranted.^20,23

Baroreceptor reflex function is altered with aging.24 Baroreceptors, located at the bifurcation of the common carotid artery and aortic arch, are mechanoreceptors that respond to stretch and other changes in the blood vessel wall.²⁵ Impulses arising in the baroreceptor region project to the vasomotor center (nucleus of tractus solitarius) in the medulla. Abrupt changes in blood pressure caused by increases in peripheral resistance, CO, or blood volume are sensed by the baroreceptors, resulting in an increase in the impulse frequency to the vasomotor center within the medulla. This increase inhibits vasoconstrictor impulses arising from the vasoconstrictor region within the medulla.²⁵ The result is a decrease in heart rate (HR) and peripheral vasodilation; both these effects return the blood pressure to within normal limits.

Postural hypotension was once thought to occur more frequently in older persons and to be related to age. However, recent studies have shown that the prevalence of postural hypotension is quite low in older persons.^26,27 The prevalence of orthostatic hypotension is greater in institutionalized older patients who are receiving antihypertensive medications.²⁸

In most individuals, aging is associated with a decline in exercise performance. The thickening of the left ventricular wall along with stiffening of the aortic and mitral valves makes the aging heart less able to provide adequate contractile strength.29 With advancing age the maximal HR achieved during exercise is attenuated; however, the decreased HR response is accompanied by an increase in LVEDV and SV. This augmentation in LVEDV and SV offsets the attenuated HR response and maintains CO in exercise.

Healthy older persons have no age-associated decline in CO during exercise, but other factors (e.g., neural functioning, skeletal/joint functioning, pulmonary function) may limit an older individual’s ability to exercise.

The effects of aging on the peripheral vascular system are reflected in the gradual but linear rise in systolic blood pressure.30,31 Diastolic blood pressure is less affected by age and generally remains the same or decreases.³¹

Important determinants of systolic blood pressure include the compliance of the vasculature and the blood volume within the vascular system. Similar to the heart, the compliance of the vasculature is determined by its cell type and tissue composition. With advancing age the intimal layer thickens, principally because of an increase in smooth muscle cells that have migrated from the medial layer, and the amount of connective tissue (collagen, elastic tissue) increases.³⁰ These changes occur in the intima of the large and distal arteries. This gradual decrease in arterial compliance, or “stiffening of the arteries,” is known as arteriosclerosis. Arteriosclerotic and atherosclerotic processes cause the arteries to become progressively less distensible, altering the vascular pressure-volume relationship. These changes are clinically significant because small changes in intravascular volume are accompanied by disproportionate increases in systolic blood pressure. The decrease in arterial compliance and disproportionate increase in systolic blood pressure may lead to an increase in afterload and the development of concentric (pressure-induced) ventricular hypertrophy in the elderly patient.³²

Arterial pressure is also governed by the amount of blood volume, which in turn is regulated by plasma levels of sodium and water and the activity of the renin-angiotensin system.³³ Plasma renin activity declines with age, and aging per se has no appreciable effect on sodium and water homeostasis.^34,35 As noted later, however, age-related changes occur in renal tubular function, and the glomerular filtration rate (GFR) decreases, both of which can affect overall sodium and water homeostasis. Circulating levels of sodium-regulating hormones, such as natriuretic hormone, aldosterone, and antidiuretic hormone (ADH), are not appreciably altered by advancing age.^35,36 However, a delayed natriuretic response after sodium loading and plasma volume expansion and a diminished renal response to ADH secretion have been reported in older persons.³⁶

Upper airway changes include weakening support of upper and lower cartilage, predisposing older persons to obstructive changes. Submucosal glands decrease production of mucus, leading to dryness and thickened secretions.38 With advancing age the chest wall (thoracic skeleton) and vertebrae undergo a small degree of osteoporosis, and at the same time the costal cartilages that connect the rib cage together become calcified and stiff. These changes may produce kyphosis and reduce chest wall compliance, respectively.^37,39,40 The functional effect is a decrease in thoracic wall excursion. Other factors, such as an increase in abdominal girth and change in posture, also decrease thoracic excursion. These anatomic changes are reflected by an increase in residual volume and decrease in vital capacity.

The strength of the respiratory muscles (diaphragm, external/internal intercostal muscles) gradually decreases. Respiratory muscle weakness begins as early as age 55.⁴¹ During aging, skeletal muscle progressively atrophies and its energy metabolism decreases, which may partially explain the declining strength of the respiratory muscles.^42,43 In addition, an age-associated decrease occurs in the effectiveness of the cough reflex, possibly caused by a decrease in ciliary responsiveness and motion.⁴⁴

With advancing age a diminished recoil (or increased compliance) of the lung occurs.45 The reduced recoil results from the increase in the ratio of elastin to collagen content that occurs with advancing age.⁴⁶ Collagen, elastin, and reticulin are the primary connective tissue proteins of the lung tissue.^47,48 They are responsible for the elasticity and performance of the airways of the lung. Whereas total lung collagen remains unaltered, the amount of elastin increases with age in the interlobular septa and pleura and possibly within the bronchi and their vessels. These anatomic changes are reflected by an increase in residual volume and a decrease in forced expiratory volume. With changes in cartilage the trachea and bronchi become stiffer and less compliant.³⁸ Also, the size of the alveolar ducts increases after age 40.³⁷ The bronchial enlargement displaces inhaled air volume away from the alveoli that line the alveolar ducts (Figure 7-2).

Ventilation and oxygen/carbon dioxide exchange (diffusion) depend on numerous factors, including the surface area available for diffusion. A displacement of inhaled air volume away from the alveoli limits the surface area available for gas exchange. This may partly explain the progressive and linear decrease in the pulmonary diffusion capacity, which depends on both surface area and capillary blood volume. Capillary blood volume and surface area have been reported to decrease with advancing age.⁴⁹

The arterial oxygen tension (PaO₂) decreases with age, such that the median PaO₂ for healthy persons older than 60 years is 74.3 mm Hg, as compared with 94 mm Hg for younger adults.50 In contrast, arterial carbon dioxide (PaCO₂) does not change with advancing age (see Table 7-2).⁵⁰ The decrease in Pao₂ may be the result of an increase of air trapping as the result of a ventilation/perfusion mismatch.^51,52 Consequently, dependent lung zones may be ventilated intermittently, leading to regional differences in ventilation. It is possible that alterations in blood volume and vascular resistance within the pulmonary circulation may also contribute to ventilation/perfusion (V/Q) mismatching. Other factors, such as smoking and pulmonary disease, also have an impact on the level of arterial oxygenation.

With advancing age, total lung capacity and tidal volume do not change.39 Residual volume (RV) increases with age, paralleling the decrease in chest wall compliance and reduced strength of the respiratory muscles. The increase in RV may also add to the diminished strength of the inspiratory muscles by stretching the diaphragm and altering the tension-length relationship.

GFR decreases with advancing age.58,59 In older persons the decrease in GFR is most likely caused by the decrease in nephron number as well as decreased renal blood flow.⁵⁸

Even though the remaining nephrons adapt to the loss of nephrons by glomerular hyperfiltration and increased solute load per nephron, the reduced GFR predisposes the elderly patient to adverse drug reactions and drug-induced renal failure. Some drugs are excreted unchanged in the urine, whereas other drugs have active or nephrotoxic metabolites that are excreted in the urine. In addition, the senescent kidney is more susceptible to injury by hypotensive episodes because of the age-related decrease in renal blood flow and reduced pressure gradient across the afferent arteriole.⁶⁰

Age-related changes also occur in tubular function. The age-related changes in tubular function become apparent when extreme changes occur in the body fluid composition or acid-base balance. For example, with systemic acidosis the rate and amount of total acid excretion (bicarbonate, titratable acid, ammonium) are reduced.^58,60 This predisposes the older patient to metabolic acidosis, volume depletion, and hyperchloremia. At a normal pH level, however, the kidney of an older person can maintain acid-base homeostasis.

The senescent kidney has diminished capability to excrete a free water load, conserve water during periods of dehydration, and conserve sodium during periods of low salt intake.⁵⁸ Older persons are at high risk for dehydration because of these renal changes, along with decreased overall total body water, decreased concentrating ability, and decreased thirst perception.⁶¹ Age-related changes also occur in extrarenal mechanisms, such as the decreased activity and responsiveness of the senescent kidney to the sympathetic nervous system and renin-angiotensin-aldosterone system, which are important in integrating overall fluid homeostasis and maintaining blood pressure in response to changes in body position.³⁴

With advancing age, both hepatocyte number and liver weight decrease.70 Total liver blood flow decreases by 50% between 25 and 65 years of age.^70–72 The liver has many complex functions, including carbohydrate storage, ketone body formation, reduction/conjugation of adrenal and gonadal steroid hormones, synthesis of plasma proteins, deamination of amino acids, storage of cholesterol, urea formation, and detoxification of toxins and drugs. Despite changes in hepatocyte number and blood flow, however, liver function is not appreciably altered.⁷² Several liver function tests, including serum bilirubin, alkaline phosphatase, and aspartate aminotransferase (AST) levels, are not altered with advancing age. However, because of the decrease in total liver blood flow, first-pass clearance of drugs is somewhat reduced. The most important age-related change in liver function is the decrease in the liver’s capacity to metabolize drugs.^73,74 Although liver function tests do not reflect this change in metabolism, it is well recognized that drug side effects and toxic effects occur more frequently in older adults than in young adults.⁷⁴

Cognitive functioning involves the process of transforming, synthesizing, storing, and retrieving sensory input. Additional components include perception, attention, thinking, memory, and problem solving. For the aging individual, cognition is altered by the speed at which information is processed and retrieved.75 Performance on timed tests declines slowly after age 20. Intelligence remains fairly stable after age 30 until the mid-80s. Although the rate at which complex tasks are completed may be diminished, these age-related changes are not synonymous with cognitive impairment.

Marked deterioration of any component of cognitive functioning is not a normal expectation of the aging process.⁷⁶ Cognitive impairment in older adults more often results from acute and chronic etiologies. Acute problems such as infection, electrolyte imbalance, and pharmacological toxicity are generally reversible once identified. Long-term chronic impairment develops from more organic causations, such as multi-infarct dementia or Alzheimer’s disease.⁷⁷

The brain decreases approximately 20% in size between 25 and 95 years of age (Figure 7-3).⁷⁸ The reduced brain weight may be related in part to the overall decrease in the number of neurons that occurs with advancing age. Neurons are lost from the hippocampus, amygdala, and cerebellum and from areas of the brainstem such as the locus ceruleus, dorsal motor nucleus of vagus nerve, and substantia nigra.⁷⁵ In contrast, very few neurons disappear with advancing age in areas such as the hypothalamus.⁷⁷ In addition, portions of the cerebral cortex atrophy, principally the frontal (superior frontal gyrus) and temporal (superior temporal gyrus) cortical association areas.⁷⁸

The cerebral ventricles enlarge and develop an asymmetric appearance. Cerebrospinal fluid (CSF) also accumulates in the ventricles, although total brain CSF is not increased.⁷⁹ Accompanying the loss of neurons are changes in the ultrastructure and intracellular structures of the neuron.⁸⁰ Also, neuron shrinkage and degenerative changes in the cell bodies and axons of certain acetylcholine-secreting neurons have been reported. There are also increases in norepinephrine and dopamine synthesis.⁸¹ These changes may explain alterations in processing and receiving information.⁷⁷

In the senescent brain, synaptogenesis (synaptic regeneration) still occurs after partial nerve degeneration. After a nerve fiber is damaged, neighboring undamaged neurons often sprout new fibers and form new connections. However, synaptogenesis occurs at a slower rate in the older brain.⁸⁰

Cerebral blood flow decreases with advancing age. This decrease parallels the decrease in brain weight and is most likely caused by the reduction in neuron number and metabolic needs of the cerebral tissue.82

Immune system function depends on many cell types with distinct functions. T cells are the primary effector of cell-mediated immunity, whereas bone marrow-derived B cells produce antibodies that are the effector cells of humoral-mediated immunity.83,85,87 With aging, cell-mediated immunity declines. Even though the total number of T cells remains unchanged with advancing age, T-cell function decreases.^85,87 For example, there is a decrease in T-cell production of interleukin-2 (IL-2) and in differentiation of T cells into effector cells. IL-2 is essential for activating B cells, which eventually differentiate into antibody-secreting cells. Subsets of T cells mature into cytotoxic cells, whereas other T cells activate B cells and stimulate B-cell proliferation. Changes in B-lymphocyte function are not as well understood, even though with age the ability of B cells to produce antibodies into new antigens declines.^83,85

Furthermore, inadequate emptying of urine secondary to bed rest, obstruction, or side effects from anticholinergic medications can result in stagnation of urine and recurrent urinary tract infections. Long-term placement of urinary catheters is a significant source of bacteriuria. However, treatment with antibiotic therapy is not indicated unless the patient becomes symptomatic with anorexia or cognitive impairment or has a history of a chronic illness such as diabetes or chronic obstructive pulmonary disease.^83,88