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Special Article |

Physiological Features of Aging Persons FREE

Oliver O. Aalami, MD; Tony D. Fang, MD; HanJoon M. Song, MD; Randall P. Nacamuli, MD
[+] Author Affiliations

From the Departments of Surgery, University of California, San Francisco[[ndash]]East Bay (Drs Aalami and Nacamuli), and Stanford University School of Medicine, Stanford, Calif (Drs Fang and Song).


Arch Surg. 2003;138(10):1068-1076. doi:10.1001/archsurg.138.10.1068.
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Between 1960 and 1994, the population of those 85 years and older in the United States grew 274%.1 Similarly, the fastest-growing sector of surgical patients older than 65 years is those older than 85 years.2 These figures are critical because elderly persons have the highest mortality in the adult surgical population (5.8%-6.2% in those >80 years in 500 consecutive patients requiring general or regional anesthesia and 8.4% in those >90 years in 795 in-house operations).35 Why do elderly persons face such high surgical mortality rates? In addition to a higher incidence and prevalence of disease, elderly persons experience baseline physiological changes associated with senescence.6 It is vital for the modern surgeon to be aware of the physiological changes associated with aging to minimize morbidity and mortality in the aging surgical population.

Multiple theories of aging exist, all of which are controversial and largely unproved. In general, theories of aging are divided into either extrinsic (stochastic) or intrinsic (developmental-genetic) causes. The stochastic theories point to cumulative cellular damage from free radicals and radiation, errors in protein synthesis, and protein cross-linking.79 Developmental-genetic theories hypothesize intrinsic, preprogrammed, genetic control of cellular aging. The neuroendocrine and immunologic theory and the concept of aging genes fit into this latter category.1012 Hayflick13 studied cellular senescence across multiple species, and noted that the maximum lifespan of a fibroblast varied among species. Specifically, there was a linear relationship between the maximum fibroblast population doubling and the maximum lifespan of a given species. Other cellular studies14 have introduced the concept of telomere shortening representing an internal cellular clock.

In this review, critical physiological changes of systems associated with aging are discussed. In addition, the blunted responses of each system in the face of perioperative stresses are examined.

Normal physiological changes occur in the cardiovascular system with aging. There is a progressive loss of myocytes with a reciprocal increase in myocyte volume in both ventricles.15 The large vessels stiffen, as does the myocardium. As a result, afterload is increased and early diastolic filling is impaired. The β-adrenergic responsiveness of the heart decreases, limiting the maximum achievable heart rate (HR). In addition, the number of pacemaker cells in the sinus node decreases with age. The duration of myocardial contractility is lengthened, but force does not decrease significantly in elderly persons. The heart partially compensates for lower HRs and maximal left ventricular (LV) contractility with exercise-induced dilatation of the left ventricle.16 Despite these compensatory mechanisms, and because of the prevalence of cardiac disease, myocardial infarctions have been reported as the leading cause of postoperative death among 80-year-old patients.4

Cross-sectional echocardiographic studies17 suggest that LV wall thickness progressively increases with age independent of cardiovascular risk factors such as hypertension. Furthermore, a histomorphometric analysis18 has revealed that enlarging cardiac myocytes (hypertrophy) rather than an increase in number (hyperplasia) accounts for ventricular wall thickening; however, the absolute number of myocytes actually decreases over time. In addition, the local collagen concentration and its properties are altered in elderly persons. The number of collagen fibers increases along with increases in nonenzymatic cross-linking. Although the myocyte-collagen ratio remains relatively unchanged, this is mainly because of increased myocyte size; as a result, hypertrophy rather than hyperplasia is more prominent in elderly persons. These anatomical and structural changes contribute to an increase in myocardial stiffness and a decrease in compliance.

Previous reports17 have estimated that the LV early diastolic filling rate progressively decreases and reaches only 50% of the peak rate by the age of 80 years. The LV end-diastolic volume does not reduce with age, but does mildly increase while at rest and during upright exercise.16 This is mainly because of increased atrial contraction during the latter phase of ventricular filling. The increased contractility of the atrium will lead to hypertrophy and enlargement of the chamber, which can be detected by an atrial gallop on auscultation.19 Although the LV ejection fraction ([LV end-diastolic volume − LV end-systolic volume]/LV end-diastolic volume) is relatively preserved with age, the maximum LV ejection fraction (the ejection fraction during exhaustive upright exercise) decreases. This is because of the dramatic reduction in ejection fraction reserve during aging.17 The stroke volume remains unchanged over time, and is achieved by increasing end-diastolic volume and maximally using the Starling curve.

The resting HR does not change with age, but the maximum achievable HR decreases, with the maximal HR that an 85-year-old person can achieve being approximately 70% of that of a 20-year-old person.17 Because the stroke volume does not change over time, the maximum cardiac output (stroke volume × HR) decreases during aging, indicating that the overall cardiac reserves diminish with age. The dysfunction of sympathetic modulation of the cardiovascular system with advanced age is consistent with increased spillover of catecholamine and impaired responses to α-adrenergic receptor stimulation.20,21 This results in further reduction of the contractility of the myocardium.17 Aging also affects the LV afterload and vascular-ventricular load matching. This mismatch leads to failures of LV elasticity (contractility) in response to increased afterload.22 In addition, the diastolic pressure decreases with age, compromising myocardial perfusion and worsening overall cardiac function.

Normal aging affects the arterial system. Intimal hyperplasia and thickening, with a concomitant decrease in vascular compliance and increased stiffness, develop with advanced age,23,24 with the intimal thickness of the carotid artery increasing 2 to 3 times between the ages of 20 and 90 years.25 Multiple studies19,25 have demonstrated that intimal thickening is a risk factor for silent coronary artery disease, and it is, therefore, considered a component of subclinical vascular disease. Microscopically, there are alterations in the vascular media. Increased nonenzymatic collagen cross-linking, similar to collagen-associated changes in the myocardium, is seen. The elastin content in the media decreases with age. This contributes to decreased vascular elasticity (compliance) and increased stiffness. Pulmonary vessels of elderly persons have a lower elastin content and experience a decrease in collagen content by 1% a year.26 Lower extremity arteries of patients older than 50 years commonly demonstrate medial calcifications and sclerosis.27 Dysfunctional endothelial vascular smooth muscle tone regulation (eg, a decrease in nitric oxide production with age) contributes to stiffer arterial walls independent of atherosclerotic changes.28,29

Peripheral vascular resistance and central artery stiffness are 2 main determinants of arterial blood pressure. Increases in peripheral vascular resistance lead to an increase in systolic and diastolic pressure, while increases in central artery stiffness lead to an elevation in systolic pressure but a reduction in diastolic pressure.25 Although blood pressure in younger individuals is primarily dictated by peripheral vascular resistance, with aging central arterial stiffness becomes the main determinant of pressure.25 Investigators30 have demonstrated that systolic blood pressure increases in adults of all ages, well into the 80s, while diastolic blood pressure peaks in the 50s and subsequently declines. Thus, the overall effect of aging (disallowing for hypertension) is an increase in systolic pressure and a decrease in diastolic pressure, which manifests as a widened pulse pressure. The most common form of hypertension in adults older than 50 years is isolated systolic hypertension.31 Increased systolic pressure, although used as a screening variable for increased cardiovascular disease risk, is not as good a predictor of coronary disease as is increased pulse pressure.3234

Normal aging results in changes in pulmonary mechanics, respiratory muscle strength, gas exchange, and ventilatory control. Increased rigidity of the chest wall and a decrease in respiratory muscle strength with aging result in an increased closing capacity and a decreased forced expiratory volume in 1 second (FEV1).35 The partial pressure of oxygen, arterial, decreases progressively with age because of the age-induced ventilation-perfusion mismatch, diffusion block, and anatomical shunt.36 Also, elderly patients have a diminished ventilatory response to hypercapnia and hypoxia.37

The large airways grow slightly with age, but the resulting increase in dead space is insignificant.38 The respiratory bronchioles and alveolar ducts, on the other hand, increase in size significantly over time, particularly after the age of 60 years. The fraction of lung consisting of alveolar ducts increases progressively over time. As the alveoli grow, the cumulative surface area available for gas exchange decreases by 15% by the age of 70 years.39

Changes associated with aging result in a diminishing pulmonary elastic recoil pressure.40 The fusion of adjacent alveoli, which occurs with aging, decreases surface tension forces and pulmonary elastic recoil.38 In addition, chest wall stiffness increases with advancing age, decreasing compliance. Chest wall stiffness increases because of the calcification of intercostal cartilages, arthritis of the costovertebral joints, and gradual atrophy and weakening of the intercostal muscles with advanced age. A patient with kyphosis or osteoporosis has an even more significant decrease in chest wall compliance.41 Elastin fiber concentration surprisingly increases with age, and is not believed to contribute to the age-related decrease in lung elasticity.42

Gradual atrophy and weakening of the intercostal muscles during aging demands greater contributions from the diaphragm and abdominal muscles for breathing. Unfortunately, the strength of the diaphragm declines with age, as measured by the maximum transdiaphragmatic pressure.43,44

Pulmonary function test changes are most affected by the age-related decreased compliance of the pulmonary system and muscle strength. Burr et al45 showed that the FEV1 and the forced vital capacity decline progressively with age. Knudson et al35 estimated that the FEV1 decreases by 30 and 23 mL/y in nonsmoking men and women, respectively, with an even greater decrease after the age of 65 years. This is equivalent to an 8% to 10% decline in FEV1 each decade. The forced vital capacity in nonsmokers is estimated to decrease about 15 to 30 mL/y.46,47 The vital capacity progressively decreases and the residual volume gradually increases, leading to a relatively unchanged total lung capacity (vital capacity + residual volume). The functional residual capacity also increases with age, although it is not as significant because of the counteraction of the increased stiffness of the chest wall.48

Immunohistochemical staining of type IV collagen in alveoli showed increased thickness of the alveolar basement membrane.49 Thickening of the alveolar basement membrane decreases gas-diffusing capabilities. The diffusing capacity of the lung is decreased about 2.03 mL/min per millimeter of mercury in men per decade and 1.47 mL/min per millimeter of mercury in women per decade.50 The resulting ventilation-perfusion mismatch leads to higher alveolar-arterial oxygen gradients. The partial pressure of oxygen, arterial, decreases during rest and exercise with age, becoming more prominent during exercise.

Collectively, the normal aging process changes the anatomical structures and tissue properties affecting respiratory physiological features in several aspects. Most important, expiratory flow rates decrease with age, as does the partial pressure of arterial oxygen. Both of these functional variables have been reported as risk factors for pulmonary complications.51 Age-related pulmonary function changes result in decreasing respiratory reserves. In the perioperative period, special care must be taken not to compromise the patient's respiratory function. Preventing aspiration and fluid overload and encouraging pulmonary toilet are just some examples.

The kidneys grow from 50 to 250 g in the first 50 years of life. In contrast, their weight decreases from the age of 50 years to 180 g.52 Dunnill and Halley53 have demonstrated that this absolute volume loss is primarily due to cortical tissue loss. The renal medulla, in comparison, maintains most of its volume. Cortical loss is due to glomerulosclerosis (acellular obliteration of glomerular capillary architecture).54 Shunts form around sclerotic glomeruli, decreasing cortical blood flow while maintaining flow to the medulla and the collecting system parenchyma.55,56 Hypertension, diabetes mellitus, and atherosclerosis accelerate the process of glomerulonephrosis.54 In addition, tubular senescence is seen in the elderly population.57 Histologically, tubular length decreases, interstitial fibrosis is seen, and tubular basement membrane constitution and anatomical features change with age.

Glomerulosclerosis directly affects the glomerular filtration rate (GFR). After the age of 40 years, the GFR decreases 1 mL/min per year.58 Because of the concomitant decrease in creatinine production in elderly persons, serum creatinine levels remain normal despite significantly reduced GFRs.54 The elderly patient undergoing surgery has a low filtration reserve and is, therefore, more sensitive to any ischemic or nephrotoxic insults. Fluid, electrolyte, and acid-base abnormalities result, with the onset of acute renal failure.

Tubular senescence blunts the reabsorption and secretion of solutes. Specifically, the capacity to reabsorb sodium decreases, as does the secretion of potassium and hydrogen ions.59 The juxtaglomerular apparatus in elderly patients produces less renin than in young patients, blunting the response to aldosterone.60 As a consequence, elderly patients are more susceptible to electrolyte and acid-base abnormalities. Antidiuretic hormone response is also attenuated in elderly persons, making sodium and water conservation difficult.61,62

Reduced renal reserve is seen in the disease-free elderly population. Glomerulosclerosis and senescence of tubules are the 2 main causes of decreased GFR with aging. In the face of surgery, fluid, electrolyte, and acid-base balance must be monitored closely to correct any abnormalities. Elderly patients poorly tolerate dehydration and volume loads. They are more likely to accumulate potassium, and have a blunted renin response. The response to aldosterone and vasopressin is also blunted. In addition, because of the diminished GFR of elderly persons, drugs that are cleared via the kidneys require dose modification based on creatinine clearance.63 If such precautions are not taken, toxic levels will accumulate in the circulation.

Alterations in normal gastrointestinal physiological features can be generally broken down into 3 areas: changes in neuromuscular function, changes in the structure of the gastrointestinal tract itself, and changes in the absorptive and secretory functions of the bowel. Neuromuscular changes primarily affect the upper gastrointestinal tract, particularly the esophagus, and can lead to symptoms consistent with numerous disease processes, such as reflux and achalasia. Changes in the structure of the bowel wall are most notable distally in the colon, and are responsible for the most common age-related colonic disorder, diverticula.64 Functional alterations in secretion and absorption are predominantly found in the stomach (secretion) and small bowel (absorption), although it is difficult to consistently link these age-related changes with pathological features.

Changes in Neuromuscular Function

Changes in function with aging of the oropharynx and esophagus are primarily related to neuromuscular degeneration and subsequent alterations in the ability to coordinate the complex reflexes that lead to successful swallowing and propulsion of food along the esophagus. Aberrant contraction can also be caused by weakness in the muscles. Failure to coordinate the reflexes regulating proper motility can lead to numerous pathological features, including diffuse esophageal spasm, achalasia, and reflux. Because these age-associated problems with esophageal motor function can also be caused by primary neurological conditions, it is especially important to delineate deficits in neurological function caused by cerebrovascular accidents and true central nervous system degenerative processes from age-related changes.65 The cricopharyngeus muscle, the primary muscle of the upper esophageal sphincter, is particularly susceptible to alterations in motility and may lead directly to problems such as aspiration, dysphagia, and pharyngoesophageal diverticula.66,67 Neuromuscular deficits of the lower esophagus include a decreased or even absent response to normal upper esophageal peristalsis, with a general weakness and slowing of contractions. Insufficient resting pressure in the lower esophageal sphincter can lead to gastroesophageal reflux and symptoms simulating hiatal hernia and achalasia.68

The other portion of the gastrointestinal tract thought to experience altered neuromuscular function with age is the stomach. However, the exact effect that aging has is unclear. Studies69,70 investigating the gastric emptying times of young and elderly patients have demonstrated increases and decreases in the rate of emptying. Furthermore, it has been challenging to link any alteration in gastric emptying with patient complaint or pathological features.68 At best, these data suggest that there may be perturbations in the homeostatic mechanisms regulating gastric emptying in elderly persons. The small bowel has been demonstrated to have unaltered rates of transit.69

Changes in Gastrointestinal Wall Structure

The upper alimentary tract does not experience significant structural changes as age progresses. As mentioned previously, weakening of the musculature of the oropharynx and upper esophagus can contribute to the formation of pharyngoesophageal diverticula and can cause functional problems. Similarly, although the gastric mucosa becomes atrophic with age, correlations between histologic change and disease processes, including atrophic gastritis, have been hard to establish.71 The primary structures affected by age in the small bowel are intestinal villi. Starting around the age of 60 years, there is a progressive decrease in the height of the villi, with a concomitant decrease in surface area available for absorption.68 Fibrous connective tissue can also be seen replacing normal mucosal parenchyma and smooth muscle cells.

The colon is the most consistently affected portion of the gastrointestinal tract with regard to age-related structural alterations. Mucosal changes are noted, but do not affect the absorptive capabilities of the colon.68 The primary process seen in the colon is a thickening of the muscular layers, particularly the muscularis propria and the muscularis mucosa. This thickening is due to elastogenesis and a buildup of elastin between myocytes in the bowel wall, not due to muscle cell hyperplasia or hypertrophy (although these may be caused by inflammation and fibrosis).64,72 Thickening is present throughout the life cycle, but becomes more rapid after the age of 60 years. The tinea coli are affected more than the circular muscle layers, and it is contraction in the longitudinal direction secondary to elastin accumulation that contributes to hard stool, constipation, and fecal impaction. Diverticular disease, the most common age-related colonic disease, occurs as a result of concomitant weakening of the muscularis propria at locations where arteries and veins cross the bowel wall.73

Changes in Secretion and Absorption

It is a common misconception that age-associated xerostomia is due to a primary deficit in the production of saliva. Although the composition of saliva is altered in elderly persons (they have higher levels of mucin, resulting in a more viscous secretion), overall production and flow rates are normal.74,75 Diminished salivation is almost always attributable to secondary factors, such as medication. Secretion of gastric acid and pepsin declines with age. This is more noticeable in women, and is manifested as an attenuation of peak and basal acid secretion.71 However, serious problems, such as achlorhydria, are not usually attributable to age alone and, thus, the underlying pathological features in patients with this type of condition must be determined. Decreases in pepsin secretion correlate with those patients in whom age-related mucosal atrophy is present.68

In the small bowel, a decrease in the height of villi and a reduction in surface area can lead to disorders of absorption. Specifically, absorption of calcium, carbohydrate, and D-xylose is impaired, although this may be inconsistent and may not be clinically significant.68,76 There are no significant changes in the absorptive capacity of the colon attributable to age.

Several changes in liver physiological features occur with aging. The size of the liver decreases after the age of 50 years, declining from roughly 2.5% of total body mass to a nadir of just more than 1.5%. Alterations in blood flow parallel this decrease. Interestingly, although the total number of hepatocytes in an aged liver is decreased, there is an increase in the mean cell volume, which some68 have interpreted as a cellular response to an increased biological demand on the remaining cells. Despite this potential increased demand, most liver function test results remain normal in elderly persons, as do standard function test results, such as those for hepatic filtration, detoxification, ethanol elimination, and conjugation.68,77 Hepatic synthesis of several proteins, including clotting factors, can be reduced, although this does not impair baseline function. However, perhaps because of the larger anabolic burden placed on fewer hepatocytes, hepatic synthesis of these factors is unable to increase significantly beyond baseline when challenged.78

No direct link between aging and major gallbladder function has been established, including absorption, mucosal physiological features, and contractile properties. Although there is an increase in the incidence of cholelithiasis in elderly persons (theoretically attributed to an increase in the ratio of lipid-cholesterol in bile), the underlying process by which this occurs has not been elucidated.68,79

Age-related changes that occur in various endocrine functions have been well documented in the literature. Perhaps the best studied of these include postmenopausal changes, resulting in an estrogen-deficient state. Menopause is characterized by a cessation of menses and a decline in estrogen levels with a concomitant increase in luteinizing hormone and follicle-stimulating hormone levels.80 During the first decade after the initiation of menopause, women undergo rapid bone loss, most likely reflecting diminished estrogen levels. Thereafter, a slow phase of bone loss occurs, primarily from a loss of estrogen-mediated calcium homeostasis.81 The decrease in skeletal mass associated with menopause occurs in conjunction with normal age-related bone loss, further compounding the problems of osteoporosis and pathological bone fractures in elderly persons. In addition to its effects on bone, menopause removes estrogen's cardioprotective effect, increasing low-density lipoprotein level, decreasing high-density lipoprotein level, and increasing overall atherogenesis.82 Further effects of low estrogen levels experienced in menopause include changes in vasomotor symptoms, urogenital atrophy, increased mood swings, and loss of libido.83,84 Hormone therapy alleviates many of these estrogen-deficient symptoms, although well-known risks have been documented, including increased risks of venous thrombosis, stroke, and breast cancer.8587

In men, serum testosterone, estradiol, dehydroepiandrosterone, and dehydroepiandrosterone sulfate levels slowly decline with advancing age, while sex hormone–binding globulin, luteinizing hormone, and follicle stimulating hormone levels increase.88 The decrease in sex hormone–binding globulin further decreases the level of free active testosterone. Low testosterone levels are associated with decreased libido, decreased hematocrit, muscle atrophy, osteoporosis, and possibly erectile dysfunction.83,89 In older men with testosterone-related hypogonadism or markedly low levels of testosterone, testosterone replacement has been shown to improve sexual drive, increase lean body mass, and possibly improve exercise-induced coronary ischemia.90 The benefits of testosterone supplementation for older men with normal to low-normal levels of testosterone without clinical signs of hypogonadism are less clear. Overall, the long-term effects of testosterone therapy are inconclusive and warrant further investigation.9092

In terms of pituitary function, an age-related decrease in growth hormone and its anabolic mediator, insulinlike growth factor 1, may be associated with the decreased lean body and bone mass and increased percentage body fat observed in aging persons.93,94 Rather than a defect in growth hormone release from the pituitary gland, changes in growth hormone–related regulatory hormones, such as growth hormone–releasing hormone and somatostatin, seem to mediate the age-related decrease in growth hormone.95 As for other pituitary hormones, baseline prolactin levels are similar as individuals age, although the increase in prolactin levels in response to mild surgical stress (eg, inguinal hernia repair) seems to be blunted in older individuals.96

For nondiabetic individuals, progressive impairment of glucose tolerance occurs with advancing age, independent of obesity and sex.83 A previous investigation97 comparing the response of older (those in their 80s) with that of younger (those in their 20s) individuals to oral glucose tolerance tests reported a 45% rate of impaired tolerance in older individuals. The pathogenesis of this age-related decline in glucose handling seems to result from increased insulin resistance rather than an impairment of insulin secretion.98 Possible explanations for this age-related insulin resistance include a decrease in fat-free mass, dietary and physical activity changes, neurohormonal changes, and a decreased capacity of the glucose uptake system.98,99 Overall, there is an age-related increase in fasting and postprandial glucose levels.83,100 As for enzymatic function of the pancreas, pancreatic lipase may be mildly decreased, possibly accounting for the slight impairment of fat absorption observed in elderly persons.68

The anatomical features and function of the thyroid also undergo age-related changes. The thyroid gland in elderly persons is characterized by mild atrophy, increased fibrosis, and decreased size of the follicles.101 Functionally, there is less peripheral conversion of thyroxine to triiodothyronine, decreased uptake of iodine, and overall lower levels of thyroxine and free thyroxine.68,101 However, whether the age-related decline in thyroid function translates to clinical relevance is unclear. Similar to the thyroid, the neighboring parathyroid glands also undergo age-related changes. Several studies102 have demonstrated an increase in parathyroid hormone level with age and increased parathyroid hormone release in response to serum calcium compared with younger individuals. The increased baseline levels and augmented response of parathyroid hormone to stimuli have been implicated in osteoporosis and bone loss in elderly persons.103 In contrast to parathyroid hormone, calcitonin levels seem to decrease with age.

Interestingly, adrenal function in advanced age leads to changes in the diurnal pattern of cortisol, which shifts earlier in the day and produces higher evening cortisol levels.68,104 Clinically, these sleep disturbances are manifested by a relatively earlier bedtime and awakening compared with younger individuals. In addition, there is a positive correlation between increases in baseline levels of epinephrine and norepinephrine and age; however, the response of epinephrine and norepinephrine release to stimulation is blunted.83,105 The attenuated sympathetic response of body stress manifests in several ways. For instance, older individuals have less cutaneous vasoconstriction to cold stimuli compared with younger individuals, making them more susceptible to hypothermia (also described in the "Neurological Changes" section).106 Also, less reserve in elderly persons translates into decreased capacity to efficiently regulate pulse rate, blood pressure, blood pH, and oxygen use.

Apart from decreased sympathetic responsiveness during stress in elderly persons, immune function also has an age-related decline. Advanced age leads to a functional impairment of T-lymphocyte–mediated immunity and an increased susceptibility to infections.107 The response of T lymphocytes to interleukin 2 also seems to be impaired in older individuals, as is the stress-related increase in natural killer cell activity.83,108 Furthermore, markers of the systemic response to surgical stress (tumor necrosis factor α, interleukin 6, and CD11b/CD18 expression) have been elevated after surgical stress in older compared with younger individuals.109 Investigators have, thus, postulated that activation of monocytes and the increases in cytokine responses to surgical stress may potentially contribute to systemic inflammatory response syndrome and an increased incidence of postoperative complications in elderly persons. Interleukin 6, an inflammatory cytokine, has been particularly well studied, and its age-related increase has been well documented.110 In terms of function, interleukin 6 has been postulated to modulate the endocrine response, with activation of the hypothalamic-pituitary-adrenal axis, stimulation of plasma cortisol levels, and augmentation of bone loss.83,111 The role of interleukin 6 has also been reported to be sex specific.112

Traditional theories of normal neuronal loss with aging have been challenged.113 Histological studies114 of brain specimens from subjects without dementia or other cerebral pathological features have shown minimal neuronal loss with normal aging. Neurodegenerative processes (Alzheimer, Parkinson, and Huntington diseases), though, are strongly associated with neuronal loss.115117 Cortical atrophy has been repeatedly demonstrated to progress with age.118120 A 6% to 11% loss of brain weight has been demonstrated in subjects older than 80 years.121 Coffey et al119 performed quantitative magnetic resonance imaging studies of the brain in subjects matched by Mini-Mental State Examination score and found statistical decreases in cerebral hemisphere volume, frontal region area, temporoparietal region area, and parieto-occipital region area with age. Increased lateral ventricle and third ventricle volumes in elderly persons were also shown in the same study.119 Cortical atrophy is said to precede neurodegeneration, if dementia has not already ensued.121 In patients with Alzheimer disease, Mouton et al122 have demonstrated a 20% to 25% greater cortical atrophy compared with age-matched control subjects. Interestingly, higher levels of education have been shown to protect against dementia.123 This concept is known as the reserve hypothesis.

Cerebral blood flow and cerebral oxygen consumption have been shown to decrease with age, particularly in areas with decreased gray and white matter.124126 This increases the risk for cerebrovascular accidents with associated vascular disease. Vision, auditory function, and vibrotactile sensation are blunted with age.121 The receptor cells of the retina, rods, and cones have been reported to undergo changes with aging.127 Stiffening of the tympanic membrane and sensory loss of the cochlea are a few examples of changes in the auditory system.128 Decreased mechanoreceptor density and sensitivity, and decreased peripheral nerve conductivity, have been shown in elderly patients with decreased vibrotactile sensation.129 Loss of labyrinth hair cells, nerve fibers, and vestibular ganglion cells has been shown to affect the vestibulo-ocular reflex in elderly persons.130 Decreased tactile and proprioceptive sensation has been reported in elderly persons.128,131 Kokmen et al132 reported decreased joint motion sensation in healthy aged individuals. They found a decrease in reflex time with age, but no difference in nerve fiber numbers.132

The autonomic neural responses are blunted in elderly persons. Collins et al133 found healthy elderly subjects to have significantly diminished beat-to-beat variation in response to postural change, decreased vasoconstrictor response to cooling, and reduced baroreflex sensitivity. Peripheral vascular resistance is maintained with postural changes in healthy community-dwelling elderly individuals, despite blunting of the baroreflexes with age.134,135 Orthostatic intolerance is far more common in debilitated patients older than 70 years who are institutionalized for the long term.136 Pfeifer et al137 reported an age-related increase in cardiovascular sympathetic activity and a decrease in cardiac parasympathetic activity. Brodde and Michel138 attribute the diminished sympathetic tachycardia response and the diminished vagal bradycardia response of the aging heart to the reduced responsiveness of α-adrenergic and muscarinic receptors, respectively. Thermoregulatory mechanisms become less responsive with age, predisposing elderly persons to hypothermia in cold environments.43,139141 The 2 primary responses to a cold challenge, vasoconstriction and shivering, are less effective.141,142 After a cold isotonic sodium chloride solution infusion in elderly patients, Frank et al143 reported a decreased maximum response intensity for vasoconstriction, total body oxygen consumption, and norepinephrine. In addition, decreased vasomotor responsiveness to norepinephrine and subjective sensory thermal perception were noted.143

Elderly persons have an increased threshold for pain.144 Adequate pain control is critical to minimize the risk for myocardial ischemia, tachycardia, hypertension, and pulmonary complications. In addition, effective analgesia encourages early patient mobilization, shortens hospital stays, and decreases medical costs.51 At the same time, caution must be taken not to overmedicate elderly persons. Overmedication with various agents may lead to hypoxia, hypercapnia, hypotension, or delirium. Agents with shorter elimination half-lives are recommended.145

In summary, cortical atrophy lowers the threshold to neurodegeneration in patients. The most common postoperative neural complications are cerebrovascular accidents and delirium. Perioperative insults, such as hypotension, hypoxia, hypothermia, and malnutrition, pose a greater risk to the central nervous system of elderly persons compared with young persons. The blunted sympathetic and parasympathetic responses to stimuli result in more moderate responses to stress and typically longer recovery times to baseline functionality.

Elderly persons experience normal physiological changes associated with aging in all of their solid organ systems. Together, these changes lead to a diminished physiological reserve. Patients with advanced age have the highest mortality rate within the adult surgical population.3 A major risk factor for perioperative mortality is, therefore, considered to be advanced age.146 The effects of postoperative stresses are more detrimental to some organ systems than others. Myocardial infarctions have been reported as the leading cause of postoperative death among 80-year-old patients.4 Among patients older than 60 years, the incidence of postoperative myocardial infarction after noncardiac surgery is reported to be 0.1% to 0.15%, with a subsequent mortality of 50% to 83%.147 Mortality secondary to pulmonary complications is reported as between 0% and 0.6%, depending on risk factors.148,149 Pulmonary complications, including pneumonia, hypoventilation, hypoxia, and atelectasis, are reported to occur in 2% to 10% of elderly patients.3 Cerebrovascular-related mortality in elderly patients undergoing urological procedures was reported to be 0.05%.3 Postoperative delirium varies between 5% and 61%, but only 1% of patients have persistent symptoms.150,151

The perioperative risk for mortality is heightened in the postoperative period.3 The postoperative period is physiologically most stressful, because this is when there are the greatest shifts in fluid, body temperature, adrenergic activity, and pulmonary function.152 Thorough preoperative assessment of organ function and reserve, intraoperative control of disease, close postoperative monitoring, and pain management are recommended to effectively decrease perioperative mortality.51

Corresponding author: Randall P. Nacamuli, MD, Children's Surgical Research, 257 Campus Dr, Stanford, CA 94305 (e-mail: Nacamuli@stanford.edu).

Accepted for publication April 27, 2003.

Bureau of the Census, Sixty-five Plus in the United States: Statistical Brief 95. Available at: http://www.census.gov/apsd/www/statbrief/sb95_8.pdf.
Weintraub  MKekoler  L Demographics of Aging.  Baltimore, Md Williams & Wilkins1997;
Pedersen  TEliasen  KHenriksen  E A prospective study of mortality associated with anaesthesia and surgery: risk indicators of mortality in hospital. Acta Anaesthesiol Scand. 1990;34176- 182
PubMed
Djokovic  JLHedley-Whyte  J Prediction of outcome of surgery and anesthesia in patients over 80. JAMA. 1979;2422301- 2306
PubMed
Hosking  MPLobdell  CMWarner  MA  et al.  Anaesthesia for patients over 90 years of age: outcomes after regional and general anaesthetic techniques for two common surgical procedures. Anaesthesia. 1989;44142- 147
PubMed
Rosenthal  RZenilman  MKatlic  M Principles and Practice of Geriatric Surgery.  New York Springer-Verlag NY Inc2001;
Harmon  D Aging: a theory based on free radical and radiation chemistry. J Gerontol. 1956;11298- 300
Orgel  L The maintenance of accuracy of protein synthesis and its relevance to aging. Proc Natl Acad Sci U S A. 1963;49517- 521
Bjorksten  J The cross linkage theory of aging. J Am Geriatr Soc. 1968;16408- 427
PubMed
Mobbs  C Neuroendocrinology of aging. Rowe  JHandbook of the Biology of Aging. San Diego, Calif Academic Press Inc1996;234- 282
Walford  RL Immunologic theory of aging: current status. Fed Proc. 1974;332020- 2027
PubMed
Finch  CERuvkun  G The genetics of aging. Annu Rev Genomics Hum Genet. 2001;2435- 462
PubMed
Hayflick  L The limited in vitro lifetime of human diploid cell strains. Exp Cell Res. 1965;37614- 636
Harley  CB Telomere loss: mitotic clock or genetic time bomb? Mutat Res. 1991;256271- 282
PubMed
Olivetti  GMelissari  MCapasso  JM  et al.  Cardiomyopathy of the aging human heart: myocyte loss and reactive cellular hypertrophy. Circ Res. 1991;681560- 1568
PubMed
Fleg  JLO'Connor  FGerstenblith  G  et al.  Impact of age on the cardiovascular response to dynamic upright exercise in healthy men and women. J Appl Physiol. 1995;78890- 900
PubMed
Lakatta  EGLevy  D Arterial and cardiac aging: major shareholders in cardiovascular disease enterprises, part II: the aging heart in health: links to heart disease. Circulation. 2003;107346- 354
PubMed
Olivetti  GGiordano  GCorradi  D  et al.  Gender differences and aging: effects on the human heart. J Am Coll Cardiol. 1995;261068- 1079
PubMed
Lakatta  EG Arterial and cardiac aging: major shareholders in cardiovascular disease enterprises, part III: cellular and molecular clues to heart and arterial aging. Circulation. 2003;107490- 497
PubMed
Lakatta  EG Cardiovascular regulatory mechanisms in advanced age. Physiol Rev. 1993;73413- 467
PubMed
Esler  MDTurner  AGKaye  DM  et al.  Aging effects on human sympathetic neuronal function. Am J Physiol. 1995;268 (pt 2) R278- R285
PubMed
Schulman  SPGerstenblith  G Relationship of age and sex on ventricular vascular coupling at rest and exercise. Circulation. 2000;102 (suppl II) 602
Lidman  D Histopathology of human extremital arteries throughout life: including measurements of cystolic pressures in ankle and arm. Acta Chir Scand. 1982;148575- 580
PubMed
Banks  JBooth  FVMacKay  EHRajagopalan  BLee  GD The physical properties of human pulmonary arteries and veins. Clin Sci Mol Med. 1978;55477- 484
PubMed
Lakatta  EGLevy  D Arterial and cardiac aging: major shareholders in cardiovascular disease enterprises, part I: aging arteries: a "set up" for vascular disease. Circulation. 2003;107139- 146
PubMed
Mackay  EHBanks  JSykes  B  et al.  Structural basis for the changing physical properties of human pulmonary vessels with age. Thorax. 1978;33335- 344
PubMed
Mazess  RBForman  SH Longevity and age exaggeration in Vilcabamba, Ecuador. J Gerontol. 1979;3494- 98
PubMed
Avolio  A Genetic and environmental factors in the function and structure of the arterial wall. Hypertension. 1995;2634- 37
PubMed
Gimbrone Jr  MA Vascular endothelium, hemodynamic forces, and atherogenesis. Am J Pathol. 1999;1551- 5
PubMed
Franklin  SSGustin  WTWong  ND  et al.  Hemodynamic patterns of age-related changes in blood pressure: the Framingham Heart Study. Circulation. 1997;96308- 315
PubMed
Sagie  ALarson  MGLevy  D The natural history of borderline isolated systolic hypertension. N Engl J Med. 1993;3291912- 1917
PubMed
Franklin  SSLarson  MGKhan  SA  et al.  Does the relation of blood pressure to coronary heart disease risk change with aging? the Framingham Heart Study. Circulation. 2001;1031245- 1249
PubMed
Sesso  HDStampfer  MJRosner  B  et al.  Systolic and diastolic blood pressure, pulse pressure, and mean arterial pressure as predictors of cardiovascular disease risk in men. Hypertension. 2000;36801- 807
PubMed
Franklin  SSKhan  SAWong  ND  et al.  Is pulse pressure useful in predicting risk for coronary heart disease? the Framingham Heart Study. Circulation. 1999;100354- 360
PubMed
Knudson  RJLebowitz  MDHolberg  CJBurrows  B Changes in the normal maximal expiratory flow-volume curve with growth and aging. Am Rev Respir Dis. 1983;127725- 734
PubMed
Sorbini  CAGrassi  VSolinas  E  et al.  Arterial oxygen tension in relation to age in healthy subjects. Respiration. 1968;253- 13
PubMed
Kronenberg  RSDrage  CW Attenuation of the ventilatory and heart rate responses to hypoxia and hypercapnia with aging in normal men. J Clin Invest. 1973;521812- 1819
PubMed
Campbell  E Physiologic changes in respiratory function. Katlic  MPrinciples and Practice of Geriatric Surgery. New York Springer-Verlag NY Inc2001;396- 405
Thurlbeck  WMAngus  GE Growth and aging of the normal human lung. Chest. 1975;67 (2 suppl) 3S- 6S
PubMed
Pride  NB Pulmonary distensibility in age and disease. Bull Physiopathol Respir (Nancy). 1974;10103- 108
PubMed
Turner  JMMead  JWohl  ME Elasticity of human lungs in relation to age. J Appl Physiol. 1968;25664- 671
PubMed
Pierce  JHocott  JEbert  R The collagen and elastin content of the lung in emphysema. Ann Intern Med. 1961;55210- 222
Polkey  MIHarris  MLHughes  PD  et al.  The contractile properties of the elderly human diaphragm. Am J Respir Crit Care Med. 1997;1551560- 1564
PubMed
Tolep  KKelsen  SG Effect of aging on respiratory skeletal muscles. Clin Chest Med. 1993;14363- 378
PubMed
Burr  MLPhillips  KMHurst  DN Lung function in the elderly. Thorax. 1985;4054- 59
PubMed
Tockman  MSErozan  YSGupta  P  et al. LCEWDG Investigators, Lung Cancer Early Detection Group, The early detection of second primary lung cancers by sputum immunostaining. Chest. 1994;106 (suppl) 385S- 390S
PubMed
Crapo  ROMorris  AHGardner  RM Reference spirometric values using techniques and equipment that meet ATS recommendations. Am Rev Respir Dis. 1981;123659- 664
PubMed
Johnson  BDReddan  WGPegelow  DFSeow  KCDempsey  JA Flow limitation and regulation of functional residual capacity during exercise in a physically active aging population. Am Rev Respir Dis. 1991;143 (pt 1) 960- 967
PubMed
D'Errico  AScarani  PColosimo  ESpina  MGrigioni  WFMancini  AM Changes in the alveolar connective tissue of the ageing lung: an immunohistochemical study. Virchows Arch A Pathol Anat Histopathol. 1989;415137- 144
PubMed
Neas  LMSchwartz  J The determinants of pulmonary diffusing capacity in a national sample of US adults. Am J Respir Crit Care Med. 1996;153656- 664
PubMed
Jin  FChung  F Minimizing perioperative adverse events in the elderly. Br J Anaesth. 2001;87608- 624
PubMed
Roessle  RRoulet  F Nieren: In Mass und Zahl in der Pathologie.  Berlin, Germany J Springer1932;
Dunnill  MSHalley  W Some observations on the quantitative anatomy of the kidney. J Pathol. 1973;110113- 121
PubMed
Ryan  JZawada  E Renal Function and Fluid and Electrolyte Balance. 767- 779 New York Springer-Verlag NY Inc2001;
Takazakura  ESawabu  NHanda  A  et al.  Intrarenal vascular changes with age and disease. Kidney Int. 1972;2224- 230
PubMed
Epstein  M Effects of aging on the kidney. Fed Proc. 1979;38168- 171
PubMed
Darmady  EMOffer  JWoodhouse  MA The parameters of the ageing kidney. J Pathol. 1973;109195- 207
PubMed
Brenner  BMMeyer  TWHostetter  TH Dietary protein intake and the progressive nature of kidney disease: the role of hemodynamically mediated glomerular injury in the pathogenesis of progressive glomerular sclerosis in aging, renal ablation, and intrinsic renal disease. N Engl J Med. 1982;307652- 659
PubMed
Epstein  M Renal Physiologic Changes With Age.  Littleton, Colo PSG Publishing1985;
Weidmann  PDe Myttenaere-Bursztein  SMaxwell  MH  et al.  Effect on aging on plasma renin and aldosterone in normal man. Kidney Int. 1975;8325- 333
PubMed
Epstein  MHollenberg  NK Age as a determinant of renal sodium conservation in normal man. J Lab Clin Med. 1976;87411- 417
PubMed
Dontas  AMarketos  SPapanayiotou  P Mechanisms of renal tubular defects in old age. Postgrad Med J. 1972;48295- 303
Duchin  K Pharmacodynamics and Pharmacokinetics of Drugs in the Elderly.  Littleton, Colo PSG Publishing1985;
Whiteway  JMorson  BC Pathology of the ageing: diverticular disease. Clin Gastroenterol. 1985;14829- 846
PubMed
Khan  TAShragge  BWCrispin  JSLind  JF Esophageal motility in the elderly. Am J Dig Dis. 1977;221049- 1054
PubMed
Pelemans  WVantrappen  G Oesophageal disease in the elderly. Clin Gastroenterol. 1985;14635- 656
PubMed
Sivarao  DVGoyal  RK Functional anatomy and physiology of the upper esophageal sphincter. Am J Med. 2000;108 (suppl 4a) 27S- 37S
PubMed
Adkins  RBMarshall  BA Anatomic and physiologic aspects of aging. Adkins  RBScott  HWSurgical Care for the Elderly. 2nd ed. Philadelphia, Pa Lippincott-Raven Publishers1998;xxi531
Kupfer  RMHeppell  MHaggith  JW  et al.  Gastric emptying and small-bowel transit rate in the elderly. J Am Geriatr Soc. 1985;33340- 343
PubMed
Evans  MATriggs  EJCheung  M  et al.  Gastric emptying rate in the elderly: implications for drug therapy. J Am Geriatr Soc. 1981;29201- 205
PubMed
Andrews  GRHaneman  BArnold  BJBooth  JCTaylor  K Atrophic gastritis in the aged. Australas Ann Med. 1967;16230- 235
PubMed
Whiteway  JMorson  BC Elastosis in diverticular disease of the sigmoid colon. Gut. 1985;26258- 266
PubMed
Drummond  H Sacculi of the large intestine with special reference to their relations to the blood vessels of the bowel wall. Br J Surg. 1916;4407- 413
Astor  FCHanft  KLCiocon  JO Xerostomia: a prevalent condition in the elderly. Ear Nose Throat J. 1999;78476- 479
PubMed
Fischer  DShip  JA Effect of age on variability of parotid salivary gland flow rates over time. Age Ageing. 1999;28557- 561
PubMed
Holt  PR The small intestine. Clin Gastroenterol. 1985;14689- 723
PubMed
Vestal  REMcGuire  EATobin  JD  et al.  Aging and ethanol metabolism. Clin Pharmacol Ther. 1977;21343- 354
PubMed
Salem  SARajjayabun  PShepherd  AM  et al.  Reduced induction of drug metabolism in the elderly. Age Ageing. 1978;768- 73
PubMed
Valdivieso  VPalma  RWunkhaus  R  et al.  Effect of aging on biliary lipid composition and bile acid metabolism in normal Chilean women. Gastroenterology. 1978;74871- 874
PubMed
Overlie  IMoen  MHMorkrid  LSkjaeraasen  JSHolte  A The endocrine transition around menopause—a five years prospective study with profiles of gonadotropines, estrogens, androgens and SHBG among healthy women. Acta Obstet Gynecol Scand. 1999;78642- 647
PubMed
Riggs  BL Endocrine causes of age-related bone loss and osteoporosis. Novartis Found Symp. 2002;242247- 264
PubMed
Matthews  KAWing  RRKuller  LH  et al.  Influence of the perimenopause on cardiovascular risk factors and symptoms of middle-aged healthy women. Arch Intern Med. 1994;1542349- 2355
PubMed
Perry 3rd  HM The endocrinology of aging. Clin Chem. 1999;451369- 1376
PubMed
Greendale  GAJudd  HL The menopause: health implications and clinical management. J Am Geriatr Soc. 1993;41426- 436
PubMed
Johnson  SR Menopause and hormone replacement therapy. Med Clin North Am. 1998;82297- 320
PubMed
Kuller  LH Hormone replacement therapy and risk of cardiovascular disease: implications of the results of the Women's Health Initiative. Arterioscler Thromb Vasc Biol. 2003;2311- 16
PubMed
Notman  MTNadelson  C The hormone replacement therapy controversy. Arch Women Ment Health. 2002;533- 35
PubMed
Schulman  CLunenfeld  B The ageing male. World J Urol. 2002;204- 10
PubMed
Demers  LM Andropause: an androgen deficiency state in the ageing male. Expert Opin Pharmacother. 2003;4183- 190
PubMed
Gruenewald  DAMatsumoto  AM Testosterone supplementation therapy for older men: potential benefits and risks. J Am Geriatr Soc. 2003;51101- 115
PubMed
Janssens  HVanderschueren  DM Endocrinological aspects of aging in men: is hormone replacement of benefit? Eur J Obstet Gynecol Reprod Biol. 2000;927- 12
PubMed
Hermann  MBerger  P Hormonal changes in aging men: a therapeutic indication? Exp Gerontol. 2001;361075- 1082
PubMed
Corpas  EHarman  SMBlackman  MR Human growth hormone and human aging. Endocr Rev. 1993;1420- 39
PubMed
Khan  ASSane  DCWannenburg  T  et al.  Growth hormone, insulin-like growth factor-1 and the aging cardiovascular system. Cardiovasc Res. 2002;5425- 35
PubMed
Muller  EERigamonti  AEColonna Vde  GLocatelli  VBerti  FCella  SG GH-related and extra-endocrine actions of GH secretagogues in aging. Neurobiol Aging. 2002;23907- 919
PubMed
Arnetz  BBLahnborg  GEneroth  P  et al.  Age-related differences in the serum prolactin response during standardized surgery. Life Sci. 1984;352675- 2680
PubMed
McConnell  JGBuchanan  KDArdill  J  et al.  Glucose tolerance in the elderly: the role of insulin and its receptor. Eur J Clin Invest. 1982;1255- 61
PubMed
Barbieri  MRizzo  MRManzella  D  et al.  Age-related insulin resistance: is it an obligatory finding? the lesson from healthy centenarians. Diabetes Metab Res Rev. 2001;1719- 26
PubMed
Fink  RIWallace  POlefsky  JM Effects of aging on glucose-mediated glucose disposal and glucose transport. J Clin Invest. 1986;772034- 2041
PubMed
Samos  LFRoos  BA Diabetes mellitus in older persons. Med Clin North Am. 1998;82791- 803
PubMed
Sirota  DK Thyroid function and dysfunction in the elderly: a brief review. Mt Sinai J Med. 1980;47126- 131
PubMed
Haden  STBrown  EMHurwitz  S  et al.  The effects of age and gender on parathyroid hormone dynamics. Clin Endocrinol (Oxf). 2000;52329- 338
PubMed
Bilezikian  JPSilverberg  SJ Parathyroid hormone: does it have a role in the pathogenesis of osteoporosis? Clin Lab Med. 2000;20559- 567
PubMed
Van Cauter  ELeproult  RPlat  L Age-related changes in slow wave sleep and REM sleep and relationship with growth hormone and cortisol levels in healthy men. JAMA. 2000;284861- 868
PubMed
Mazzeo  RS Aging, immune function, and exercise: hormonal regulation. Int J Sports Med. 2000;21 (suppl 1) S10- S13
PubMed
Smolander  J Effect of cold exposure on older humans. Int J Sports Med. 2002;2386- 92
PubMed
Effros  RB Ageing and the immune system. Novartis Found Symp. 2001;235130- 149
PubMed
Naliboff  BDBenton  DSolomon  GF  et al.  Immunological changes in young and old adults during brief laboratory stress. Psychosom Med. 1991;53121- 132
PubMed
Ono  SAosasa  STsujimoto  H  et al.  Increased monocyte activation in elderly patients after surgical stress. Eur Surg Res. 2001;3333- 38
PubMed
Wei  JXu  HDavies  JL  et al.  Increase of plasma IL-6 concentration with age in healthy subjects. Life Sci. 1992;511953- 1956
PubMed
Giuliani  NSansoni  PGirasole  G  et al.  Serum interleukin-6, soluble interleukin-6 receptor and soluble gp130 exhibit different patterns of age- and menopause-related changes. Exp Gerontol. 2001;36547- 557
PubMed
Zietz  BHrach  SScholmerich  J  et al.  Differential age-related changes of hypothalamus-pituitary-adrenal axis hormones in healthy women and men: role of interleukin 6. Exp Clin Endocrinol Diabetes. 2001;10993- 101
PubMed
Brody  H An Examination of Cerebral Cortex and Brainstem in Aging.  New York, NY Raven Press1976;
Terry  RDe Teresa  RHansen  L Neocortical cell counts in normal human adult aging. Ann Neurol. 1987;21530- 539
PubMed
Coleman  PFlood  D Neuron numbers and dendritic extent in normal aging and Alzheimer's disease. Neurobiol Aging. 1987;8521- 545
PubMed
Meier-Ruge  WHunziker  OIwangoff  P  et al.  Alterations of Morphological and Neurochemical Parameters of the Brain Due to Normal Aging.  Amsterdam, the Netherlands Elsevier North-Holland1987;
Flood  DColeman  P Hippocampal plasticity in normal aging and decreased plasticity in Alzheimer's disease. Prog Brain Res. 1990;83435- 443
PubMed
Coffey  CELucke  JFSaxton  JA  et al.  Sex differences in brain aging: a quantitative magnetic resonance imaging study. Arch Neurol. 1998;55169- 179
PubMed
Coffey  CESaxton  JARatcliff  G  et al.  Relation of education to brain size in normal aging: implications for the reserve hypothesis. Neurology. 1999;53189- 196
PubMed
Long  DM Aging in the nervous system. Neurosurgery. 1985;17348- 354
PubMed
DeLaTorre  JFay  L Effects of aging on the human nervous system. Rosenthal  RZenilman  MKatlic  MPrinciples and Practice of Geriatric Surgery. New York Springer-Verlag NY Inc2001;926- 948
Mouton  PRMartin  LJCalhoun  ME  et al.  Cognitive decline strongly correlates with cortical atrophy in Alzheimer's dementia. Neurobiol Aging. 1998;19371- 377
PubMed
Friedland  RP Epidemiology, education, and the ecology of Alzheimer's disease. Neurology. 1993;43246- 249
PubMed
Yamaguchi  TKanno  IUemura  K Reduction in regional cerebral metabolic rate of oxygen during human aging. Stroke. 1986;171220- 1228
PubMed
Dastur  D Cerebral blood flow and metabolism in normal human aging, pathological aging, and senile dementia. J Cereb Blood Flow Metab. 1985;51- 9
PubMed
Fazekas  JAlivan  RBessman  A Cerebral physiology of the aged. Am J Med Sci. 1952;223245- 257
Marshall  JGrindle  JAnsell  P  et al.  Convolution in human rods: an aging process. Br J Ophthalmol. 1979;63181- 187
PubMed
Skinner  HBBarrack  RLCook  SD Age-related decline in proprioception. Clin Orthop. April1984;208- 211
Verrillo  RT Age related changes in the sensitivity to vibration. J Gerontol. 1980;35185- 193
PubMed
Paige  GD The aging vestibulo-ocular reflex (VOR) and adaptive plasticity. Acta Otolaryngol Suppl. 1991;481297- 300
PubMed
Kaplan  FSNixon  JEReitz  M  et al.  Age-related changes in proprioception and sensation of joint position. Acta Orthop Scand. 1985;5672- 74
PubMed
Kokmen  EBossemeyer Jr  RWBarney  JWilliams  WJ Neurological manifestations of aging. J Gerontol. 1977;32411- 419
PubMed
Collins  KJExton-Smith  ANJames  MH  et al.  Functional changes in autonomic nervous responses with ageing. Age Ageing. 1980;917- 24
PubMed
Smith  JJ Circulatory response to the upright posture.  Boca Raton, Fla CRC Press LLC1990;187
Gribbin  BPickering  TGSleight  P  et al.  Effect of age and high blood pressure on baroreflex sensitivity in man. Circ Res. 1971;29424- 431
PubMed
Lipsitz  LA Orthostatic hypotension in the elderly. N Engl J Med. 1989;321952- 957
PubMed
Pfeifer  MAWeinberg  CRCook  D  et al.  Differential changes of autonomic nervous system function with age in man. Am J Med. 1983;75249- 258
PubMed
Brodde  OEMichel  MC Adrenergic and muscarinic receptors in the human heart. Pharmacol Rev. 1999;51651- 690
PubMed
Frank  SMBeattie  CChristopherson  R  et al.  Epidural versus general anesthesia, ambient operating room temperature, and patient age as predictors of inadvertent hypothermia. Anesthesiology. 1992;77252- 257
PubMed
Inoue  YNakao  MAraki  TUeda  H Thermoregulatory responses of young and older men to cold exposure. Eur J Appl Physiol Occup Physiol. 1992;65492- 498
PubMed
Wagner  JARobinson  SMarino  RP Age and temperature regulation of humans in neutral and cold environments. J Appl Physiol. 1974;37562- 565
PubMed
Khan  FSpence  VABelch  JJ Cutaneous vascular responses and thermoregulation in relation to age. Clin Sci (Lond). 1992;82521- 528
PubMed
Frank  SMRaja  SNBulcao  C  et al.  Age-related thermoregulatory differences during core cooling in humans. Am J Physiol Regul Integr Comp Physiol. 2000;279R349- R354
PubMed
Harkins  SWChapman  CR Detection and decision factors in pain perception in young and elderly men. Pain. 1976;2253- 264
PubMed
McLeskey  CH Geriatric Anesthesiology.  Baltimore, Md Williams & Wilkins1997;
Priebe  HJ The aged cardiovascular risk patient. Br J Anaesth. 2000;85763- 778
PubMed
Plumlee  JEBoettner  RB Myocardial infarction during and following anesthesia and operation. South Med J. 1972;65886- 889
PubMed
Bluman  LGMosca  LNewman  N  et al.  Preoperative smoking habits and postoperative pulmonary complications. Chest. 1998;113883- 889
PubMed
Olsson  GLHallen  BHambraeus-Jonzon  K Aspiration during anaesthesia: a computer-aided study of 185,358 anaesthetics. Acta Anaesthesiol Scand. 1986;3084- 92
PubMed
Chung  F Postoperative mental dysfunction. McLeskey  CHGeriatric Anesthesiology. Baltimore, Md Williams & Wilkins1997;487- 495
Dai  YTLou  MFYip  PK  et al.  Risk factors and incidence of postoperative delirium in elderly Chinese patients. Gerontology. 2000;4628- 35
PubMed
Mangano  DTWong  MGLondon  MJ  et al. Study of Perioperative Ischemia (SPI) Research Group, Perioperative myocardial ischemia in patients undergoing noncardiac surgery, II: incidence and severity during the 1st week after surgery. J Am Coll Cardiol. 1991;17851- 857
PubMed

Figures

Tables

References

Bureau of the Census, Sixty-five Plus in the United States: Statistical Brief 95. Available at: http://www.census.gov/apsd/www/statbrief/sb95_8.pdf.
Weintraub  MKekoler  L Demographics of Aging.  Baltimore, Md Williams & Wilkins1997;
Pedersen  TEliasen  KHenriksen  E A prospective study of mortality associated with anaesthesia and surgery: risk indicators of mortality in hospital. Acta Anaesthesiol Scand. 1990;34176- 182
PubMed
Djokovic  JLHedley-Whyte  J Prediction of outcome of surgery and anesthesia in patients over 80. JAMA. 1979;2422301- 2306
PubMed
Hosking  MPLobdell  CMWarner  MA  et al.  Anaesthesia for patients over 90 years of age: outcomes after regional and general anaesthetic techniques for two common surgical procedures. Anaesthesia. 1989;44142- 147
PubMed
Rosenthal  RZenilman  MKatlic  M Principles and Practice of Geriatric Surgery.  New York Springer-Verlag NY Inc2001;
Harmon  D Aging: a theory based on free radical and radiation chemistry. J Gerontol. 1956;11298- 300
Orgel  L The maintenance of accuracy of protein synthesis and its relevance to aging. Proc Natl Acad Sci U S A. 1963;49517- 521
Bjorksten  J The cross linkage theory of aging. J Am Geriatr Soc. 1968;16408- 427
PubMed
Mobbs  C Neuroendocrinology of aging. Rowe  JHandbook of the Biology of Aging. San Diego, Calif Academic Press Inc1996;234- 282
Walford  RL Immunologic theory of aging: current status. Fed Proc. 1974;332020- 2027
PubMed
Finch  CERuvkun  G The genetics of aging. Annu Rev Genomics Hum Genet. 2001;2435- 462
PubMed
Hayflick  L The limited in vitro lifetime of human diploid cell strains. Exp Cell Res. 1965;37614- 636
Harley  CB Telomere loss: mitotic clock or genetic time bomb? Mutat Res. 1991;256271- 282
PubMed
Olivetti  GMelissari  MCapasso  JM  et al.  Cardiomyopathy of the aging human heart: myocyte loss and reactive cellular hypertrophy. Circ Res. 1991;681560- 1568
PubMed
Fleg  JLO'Connor  FGerstenblith  G  et al.  Impact of age on the cardiovascular response to dynamic upright exercise in healthy men and women. J Appl Physiol. 1995;78890- 900
PubMed
Lakatta  EGLevy  D Arterial and cardiac aging: major shareholders in cardiovascular disease enterprises, part II: the aging heart in health: links to heart disease. Circulation. 2003;107346- 354
PubMed
Olivetti  GGiordano  GCorradi  D  et al.  Gender differences and aging: effects on the human heart. J Am Coll Cardiol. 1995;261068- 1079
PubMed
Lakatta  EG Arterial and cardiac aging: major shareholders in cardiovascular disease enterprises, part III: cellular and molecular clues to heart and arterial aging. Circulation. 2003;107490- 497
PubMed
Lakatta  EG Cardiovascular regulatory mechanisms in advanced age. Physiol Rev. 1993;73413- 467
PubMed
Esler  MDTurner  AGKaye  DM  et al.  Aging effects on human sympathetic neuronal function. Am J Physiol. 1995;268 (pt 2) R278- R285
PubMed
Schulman  SPGerstenblith  G Relationship of age and sex on ventricular vascular coupling at rest and exercise. Circulation. 2000;102 (suppl II) 602
Lidman  D Histopathology of human extremital arteries throughout life: including measurements of cystolic pressures in ankle and arm. Acta Chir Scand. 1982;148575- 580
PubMed
Banks  JBooth  FVMacKay  EHRajagopalan  BLee  GD The physical properties of human pulmonary arteries and veins. Clin Sci Mol Med. 1978;55477- 484
PubMed
Lakatta  EGLevy  D Arterial and cardiac aging: major shareholders in cardiovascular disease enterprises, part I: aging arteries: a "set up" for vascular disease. Circulation. 2003;107139- 146
PubMed
Mackay  EHBanks  JSykes  B  et al.  Structural basis for the changing physical properties of human pulmonary vessels with age. Thorax. 1978;33335- 344
PubMed
Mazess  RBForman  SH Longevity and age exaggeration in Vilcabamba, Ecuador. J Gerontol. 1979;3494- 98
PubMed
Avolio  A Genetic and environmental factors in the function and structure of the arterial wall. Hypertension. 1995;2634- 37
PubMed
Gimbrone Jr  MA Vascular endothelium, hemodynamic forces, and atherogenesis. Am J Pathol. 1999;1551- 5
PubMed
Franklin  SSGustin  WTWong  ND  et al.  Hemodynamic patterns of age-related changes in blood pressure: the Framingham Heart Study. Circulation. 1997;96308- 315
PubMed
Sagie  ALarson  MGLevy  D The natural history of borderline isolated systolic hypertension. N Engl J Med. 1993;3291912- 1917
PubMed
Franklin  SSLarson  MGKhan  SA  et al.  Does the relation of blood pressure to coronary heart disease risk change with aging? the Framingham Heart Study. Circulation. 2001;1031245- 1249
PubMed
Sesso  HDStampfer  MJRosner  B  et al.  Systolic and diastolic blood pressure, pulse pressure, and mean arterial pressure as predictors of cardiovascular disease risk in men. Hypertension. 2000;36801- 807
PubMed
Franklin  SSKhan  SAWong  ND  et al.  Is pulse pressure useful in predicting risk for coronary heart disease? the Framingham Heart Study. Circulation. 1999;100354- 360
PubMed
Knudson  RJLebowitz  MDHolberg  CJBurrows  B Changes in the normal maximal expiratory flow-volume curve with growth and aging. Am Rev Respir Dis. 1983;127725- 734
PubMed
Sorbini  CAGrassi  VSolinas  E  et al.  Arterial oxygen tension in relation to age in healthy subjects. Respiration. 1968;253- 13
PubMed
Kronenberg  RSDrage  CW Attenuation of the ventilatory and heart rate responses to hypoxia and hypercapnia with aging in normal men. J Clin Invest. 1973;521812- 1819
PubMed
Campbell  E Physiologic changes in respiratory function. Katlic  MPrinciples and Practice of Geriatric Surgery. New York Springer-Verlag NY Inc2001;396- 405
Thurlbeck  WMAngus  GE Growth and aging of the normal human lung. Chest. 1975;67 (2 suppl) 3S- 6S
PubMed
Pride  NB Pulmonary distensibility in age and disease. Bull Physiopathol Respir (Nancy). 1974;10103- 108
PubMed
Turner  JMMead  JWohl  ME Elasticity of human lungs in relation to age. J Appl Physiol. 1968;25664- 671
PubMed
Pierce  JHocott  JEbert  R The collagen and elastin content of the lung in emphysema. Ann Intern Med. 1961;55210- 222
Polkey  MIHarris  MLHughes  PD  et al.  The contractile properties of the elderly human diaphragm. Am J Respir Crit Care Med. 1997;1551560- 1564
PubMed
Tolep  KKelsen  SG Effect of aging on respiratory skeletal muscles. Clin Chest Med. 1993;14363- 378
PubMed
Burr  MLPhillips  KMHurst  DN Lung function in the elderly. Thorax. 1985;4054- 59
PubMed
Tockman  MSErozan  YSGupta  P  et al. LCEWDG Investigators, Lung Cancer Early Detection Group, The early detection of second primary lung cancers by sputum immunostaining. Chest. 1994;106 (suppl) 385S- 390S
PubMed
Crapo  ROMorris  AHGardner  RM Reference spirometric values using techniques and equipment that meet ATS recommendations. Am Rev Respir Dis. 1981;123659- 664
PubMed
Johnson  BDReddan  WGPegelow  DFSeow  KCDempsey  JA Flow limitation and regulation of functional residual capacity during exercise in a physically active aging population. Am Rev Respir Dis. 1991;143 (pt 1) 960- 967
PubMed
D'Errico  AScarani  PColosimo  ESpina  MGrigioni  WFMancini  AM Changes in the alveolar connective tissue of the ageing lung: an immunohistochemical study. Virchows Arch A Pathol Anat Histopathol. 1989;415137- 144
PubMed
Neas  LMSchwartz  J The determinants of pulmonary diffusing capacity in a national sample of US adults. Am J Respir Crit Care Med. 1996;153656- 664
PubMed
Jin  FChung  F Minimizing perioperative adverse events in the elderly. Br J Anaesth. 2001;87608- 624
PubMed
Roessle  RRoulet  F Nieren: In Mass und Zahl in der Pathologie.  Berlin, Germany J Springer1932;
Dunnill  MSHalley  W Some observations on the quantitative anatomy of the kidney. J Pathol. 1973;110113- 121
PubMed
Ryan  JZawada  E Renal Function and Fluid and Electrolyte Balance. 767- 779 New York Springer-Verlag NY Inc2001;
Takazakura  ESawabu  NHanda  A  et al.  Intrarenal vascular changes with age and disease. Kidney Int. 1972;2224- 230
PubMed
Epstein  M Effects of aging on the kidney. Fed Proc. 1979;38168- 171
PubMed
Darmady  EMOffer  JWoodhouse  MA The parameters of the ageing kidney. J Pathol. 1973;109195- 207
PubMed
Brenner  BMMeyer  TWHostetter  TH Dietary protein intake and the progressive nature of kidney disease: the role of hemodynamically mediated glomerular injury in the pathogenesis of progressive glomerular sclerosis in aging, renal ablation, and intrinsic renal disease. N Engl J Med. 1982;307652- 659
PubMed
Epstein  M Renal Physiologic Changes With Age.  Littleton, Colo PSG Publishing1985;
Weidmann  PDe Myttenaere-Bursztein  SMaxwell  MH  et al.  Effect on aging on plasma renin and aldosterone in normal man. Kidney Int. 1975;8325- 333
PubMed
Epstein  MHollenberg  NK Age as a determinant of renal sodium conservation in normal man. J Lab Clin Med. 1976;87411- 417
PubMed
Dontas  AMarketos  SPapanayiotou  P Mechanisms of renal tubular defects in old age. Postgrad Med J. 1972;48295- 303
Duchin  K Pharmacodynamics and Pharmacokinetics of Drugs in the Elderly.  Littleton, Colo PSG Publishing1985;
Whiteway  JMorson  BC Pathology of the ageing: diverticular disease. Clin Gastroenterol. 1985;14829- 846
PubMed
Khan  TAShragge  BWCrispin  JSLind  JF Esophageal motility in the elderly. Am J Dig Dis. 1977;221049- 1054
PubMed
Pelemans  WVantrappen  G Oesophageal disease in the elderly. Clin Gastroenterol. 1985;14635- 656
PubMed
Sivarao  DVGoyal  RK Functional anatomy and physiology of the upper esophageal sphincter. Am J Med. 2000;108 (suppl 4a) 27S- 37S
PubMed
Adkins  RBMarshall  BA Anatomic and physiologic aspects of aging. Adkins  RBScott  HWSurgical Care for the Elderly. 2nd ed. Philadelphia, Pa Lippincott-Raven Publishers1998;xxi531
Kupfer  RMHeppell  MHaggith  JW  et al.  Gastric emptying and small-bowel transit rate in the elderly. J Am Geriatr Soc. 1985;33340- 343
PubMed
Evans  MATriggs  EJCheung  M  et al.  Gastric emptying rate in the elderly: implications for drug therapy. J Am Geriatr Soc. 1981;29201- 205
PubMed
Andrews  GRHaneman  BArnold  BJBooth  JCTaylor  K Atrophic gastritis in the aged. Australas Ann Med. 1967;16230- 235
PubMed
Whiteway  JMorson  BC Elastosis in diverticular disease of the sigmoid colon. Gut. 1985;26258- 266
PubMed
Drummond  H Sacculi of the large intestine with special reference to their relations to the blood vessels of the bowel wall. Br J Surg. 1916;4407- 413
Astor  FCHanft  KLCiocon  JO Xerostomia: a prevalent condition in the elderly. Ear Nose Throat J. 1999;78476- 479
PubMed
Fischer  DShip  JA Effect of age on variability of parotid salivary gland flow rates over time. Age Ageing. 1999;28557- 561
PubMed
Holt  PR The small intestine. Clin Gastroenterol. 1985;14689- 723
PubMed
Vestal  REMcGuire  EATobin  JD  et al.  Aging and ethanol metabolism. Clin Pharmacol Ther. 1977;21343- 354
PubMed
Salem  SARajjayabun  PShepherd  AM  et al.  Reduced induction of drug metabolism in the elderly. Age Ageing. 1978;768- 73
PubMed
Valdivieso  VPalma  RWunkhaus  R  et al.  Effect of aging on biliary lipid composition and bile acid metabolism in normal Chilean women. Gastroenterology. 1978;74871- 874
PubMed
Overlie  IMoen  MHMorkrid  LSkjaeraasen  JSHolte  A The endocrine transition around menopause—a five years prospective study with profiles of gonadotropines, estrogens, androgens and SHBG among healthy women. Acta Obstet Gynecol Scand. 1999;78642- 647
PubMed
Riggs  BL Endocrine causes of age-related bone loss and osteoporosis. Novartis Found Symp. 2002;242247- 264
PubMed
Matthews  KAWing  RRKuller  LH  et al.  Influence of the perimenopause on cardiovascular risk factors and symptoms of middle-aged healthy women. Arch Intern Med. 1994;1542349- 2355
PubMed
Perry 3rd  HM The endocrinology of aging. Clin Chem. 1999;451369- 1376
PubMed
Greendale  GAJudd  HL The menopause: health implications and clinical management. J Am Geriatr Soc. 1993;41426- 436
PubMed
Johnson  SR Menopause and hormone replacement therapy. Med Clin North Am. 1998;82297- 320
PubMed
Kuller  LH Hormone replacement therapy and risk of cardiovascular disease: implications of the results of the Women's Health Initiative. Arterioscler Thromb Vasc Biol. 2003;2311- 16
PubMed
Notman  MTNadelson  C The hormone replacement therapy controversy. Arch Women Ment Health. 2002;533- 35
PubMed
Schulman  CLunenfeld  B The ageing male. World J Urol. 2002;204- 10
PubMed
Demers  LM Andropause: an androgen deficiency state in the ageing male. Expert Opin Pharmacother. 2003;4183- 190
PubMed
Gruenewald  DAMatsumoto  AM Testosterone supplementation therapy for older men: potential benefits and risks. J Am Geriatr Soc. 2003;51101- 115
PubMed
Janssens  HVanderschueren  DM Endocrinological aspects of aging in men: is hormone replacement of benefit? Eur J Obstet Gynecol Reprod Biol. 2000;927- 12
PubMed
Hermann  MBerger  P Hormonal changes in aging men: a therapeutic indication? Exp Gerontol. 2001;361075- 1082
PubMed
Corpas  EHarman  SMBlackman  MR Human growth hormone and human aging. Endocr Rev. 1993;1420- 39
PubMed
Khan  ASSane  DCWannenburg  T  et al.  Growth hormone, insulin-like growth factor-1 and the aging cardiovascular system. Cardiovasc Res. 2002;5425- 35
PubMed
Muller  EERigamonti  AEColonna Vde  GLocatelli  VBerti  FCella  SG GH-related and extra-endocrine actions of GH secretagogues in aging. Neurobiol Aging. 2002;23907- 919
PubMed
Arnetz  BBLahnborg  GEneroth  P  et al.  Age-related differences in the serum prolactin response during standardized surgery. Life Sci. 1984;352675- 2680
PubMed
McConnell  JGBuchanan  KDArdill  J  et al.  Glucose tolerance in the elderly: the role of insulin and its receptor. Eur J Clin Invest. 1982;1255- 61
PubMed
Barbieri  MRizzo  MRManzella  D  et al.  Age-related insulin resistance: is it an obligatory finding? the lesson from healthy centenarians. Diabetes Metab Res Rev. 2001;1719- 26
PubMed
Fink  RIWallace  POlefsky  JM Effects of aging on glucose-mediated glucose disposal and glucose transport. J Clin Invest. 1986;772034- 2041
PubMed
Samos  LFRoos  BA Diabetes mellitus in older persons. Med Clin North Am. 1998;82791- 803
PubMed
Sirota  DK Thyroid function and dysfunction in the elderly: a brief review. Mt Sinai J Med. 1980;47126- 131
PubMed
Haden  STBrown  EMHurwitz  S  et al.  The effects of age and gender on parathyroid hormone dynamics. Clin Endocrinol (Oxf). 2000;52329- 338
PubMed
Bilezikian  JPSilverberg  SJ Parathyroid hormone: does it have a role in the pathogenesis of osteoporosis? Clin Lab Med. 2000;20559- 567
PubMed
Van Cauter  ELeproult  RPlat  L Age-related changes in slow wave sleep and REM sleep and relationship with growth hormone and cortisol levels in healthy men. JAMA. 2000;284861- 868
PubMed
Mazzeo  RS Aging, immune function, and exercise: hormonal regulation. Int J Sports Med. 2000;21 (suppl 1) S10- S13
PubMed
Smolander  J Effect of cold exposure on older humans. Int J Sports Med. 2002;2386- 92
PubMed
Effros  RB Ageing and the immune system. Novartis Found Symp. 2001;235130- 149
PubMed
Naliboff  BDBenton  DSolomon  GF  et al.  Immunological changes in young and old adults during brief laboratory stress. Psychosom Med. 1991;53121- 132
PubMed
Ono  SAosasa  STsujimoto  H  et al.  Increased monocyte activation in elderly patients after surgical stress. Eur Surg Res. 2001;3333- 38
PubMed
Wei  JXu  HDavies  JL  et al.  Increase of plasma IL-6 concentration with age in healthy subjects. Life Sci. 1992;511953- 1956
PubMed
Giuliani  NSansoni  PGirasole  G  et al.  Serum interleukin-6, soluble interleukin-6 receptor and soluble gp130 exhibit different patterns of age- and menopause-related changes. Exp Gerontol. 2001;36547- 557
PubMed
Zietz  BHrach  SScholmerich  J  et al.  Differential age-related changes of hypothalamus-pituitary-adrenal axis hormones in healthy women and men: role of interleukin 6. Exp Clin Endocrinol Diabetes. 2001;10993- 101
PubMed
Brody  H An Examination of Cerebral Cortex and Brainstem in Aging.  New York, NY Raven Press1976;
Terry  RDe Teresa  RHansen  L Neocortical cell counts in normal human adult aging. Ann Neurol. 1987;21530- 539
PubMed
Coleman  PFlood  D Neuron numbers and dendritic extent in normal aging and Alzheimer's disease. Neurobiol Aging. 1987;8521- 545
PubMed
Meier-Ruge  WHunziker  OIwangoff  P  et al.  Alterations of Morphological and Neurochemical Parameters of the Brain Due to Normal Aging.  Amsterdam, the Netherlands Elsevier North-Holland1987;
Flood  DColeman  P Hippocampal plasticity in normal aging and decreased plasticity in Alzheimer's disease. Prog Brain Res. 1990;83435- 443
PubMed
Coffey  CELucke  JFSaxton  JA  et al.  Sex differences in brain aging: a quantitative magnetic resonance imaging study. Arch Neurol. 1998;55169- 179
PubMed
Coffey  CESaxton  JARatcliff  G  et al.  Relation of education to brain size in normal aging: implications for the reserve hypothesis. Neurology. 1999;53189- 196
PubMed
Long  DM Aging in the nervous system. Neurosurgery. 1985;17348- 354
PubMed
DeLaTorre  JFay  L Effects of aging on the human nervous system. Rosenthal  RZenilman  MKatlic  MPrinciples and Practice of Geriatric Surgery. New York Springer-Verlag NY Inc2001;926- 948
Mouton  PRMartin  LJCalhoun  ME  et al.  Cognitive decline strongly correlates with cortical atrophy in Alzheimer's dementia. Neurobiol Aging. 1998;19371- 377
PubMed
Friedland  RP Epidemiology, education, and the ecology of Alzheimer's disease. Neurology. 1993;43246- 249
PubMed
Yamaguchi  TKanno  IUemura  K Reduction in regional cerebral metabolic rate of oxygen during human aging. Stroke. 1986;171220- 1228
PubMed
Dastur  D Cerebral blood flow and metabolism in normal human aging, pathological aging, and senile dementia. J Cereb Blood Flow Metab. 1985;51- 9
PubMed
Fazekas  JAlivan  RBessman  A Cerebral physiology of the aged. Am J Med Sci. 1952;223245- 257
Marshall  JGrindle  JAnsell  P  et al.  Convolution in human rods: an aging process. Br J Ophthalmol. 1979;63181- 187
PubMed
Skinner  HBBarrack  RLCook  SD Age-related decline in proprioception. Clin Orthop. April1984;208- 211
Verrillo  RT Age related changes in the sensitivity to vibration. J Gerontol. 1980;35185- 193
PubMed
Paige  GD The aging vestibulo-ocular reflex (VOR) and adaptive plasticity. Acta Otolaryngol Suppl. 1991;481297- 300
PubMed
Kaplan  FSNixon  JEReitz  M  et al.  Age-related changes in proprioception and sensation of joint position. Acta Orthop Scand. 1985;5672- 74
PubMed
Kokmen  EBossemeyer Jr  RWBarney  JWilliams  WJ Neurological manifestations of aging. J Gerontol. 1977;32411- 419
PubMed
Collins  KJExton-Smith  ANJames  MH  et al.  Functional changes in autonomic nervous responses with ageing. Age Ageing. 1980;917- 24
PubMed
Smith  JJ Circulatory response to the upright posture.  Boca Raton, Fla CRC Press LLC1990;187
Gribbin  BPickering  TGSleight  P  et al.  Effect of age and high blood pressure on baroreflex sensitivity in man. Circ Res. 1971;29424- 431
PubMed
Lipsitz  LA Orthostatic hypotension in the elderly. N Engl J Med. 1989;321952- 957
PubMed
Pfeifer  MAWeinberg  CRCook  D  et al.  Differential changes of autonomic nervous system function with age in man. Am J Med. 1983;75249- 258
PubMed
Brodde  OEMichel  MC Adrenergic and muscarinic receptors in the human heart. Pharmacol Rev. 1999;51651- 690
PubMed
Frank  SMBeattie  CChristopherson  R  et al.  Epidural versus general anesthesia, ambient operating room temperature, and patient age as predictors of inadvertent hypothermia. Anesthesiology. 1992;77252- 257
PubMed
Inoue  YNakao  MAraki  TUeda  H Thermoregulatory responses of young and older men to cold exposure. Eur J Appl Physiol Occup Physiol. 1992;65492- 498
PubMed
Wagner  JARobinson  SMarino  RP Age and temperature regulation of humans in neutral and cold environments. J Appl Physiol. 1974;37562- 565
PubMed
Khan  FSpence  VABelch  JJ Cutaneous vascular responses and thermoregulation in relation to age. Clin Sci (Lond). 1992;82521- 528
PubMed
Frank  SMRaja  SNBulcao  C  et al.  Age-related thermoregulatory differences during core cooling in humans. Am J Physiol Regul Integr Comp Physiol. 2000;279R349- R354
PubMed
Harkins  SWChapman  CR Detection and decision factors in pain perception in young and elderly men. Pain. 1976;2253- 264
PubMed
McLeskey  CH Geriatric Anesthesiology.  Baltimore, Md Williams & Wilkins1997;
Priebe  HJ The aged cardiovascular risk patient. Br J Anaesth. 2000;85763- 778
PubMed
Plumlee  JEBoettner  RB Myocardial infarction during and following anesthesia and operation. South Med J. 1972;65886- 889
PubMed
Bluman  LGMosca  LNewman  N  et al.  Preoperative smoking habits and postoperative pulmonary complications. Chest. 1998;113883- 889
PubMed
Olsson  GLHallen  BHambraeus-Jonzon  K Aspiration during anaesthesia: a computer-aided study of 185,358 anaesthetics. Acta Anaesthesiol Scand. 1986;3084- 92
PubMed
Chung  F Postoperative mental dysfunction. McLeskey  CHGeriatric Anesthesiology. Baltimore, Md Williams & Wilkins1997;487- 495
Dai  YTLou  MFYip  PK  et al.  Risk factors and incidence of postoperative delirium in elderly Chinese patients. Gerontology. 2000;4628- 35
PubMed
Mangano  DTWong  MGLondon  MJ  et al. Study of Perioperative Ischemia (SPI) Research Group, Perioperative myocardial ischemia in patients undergoing noncardiac surgery, II: incidence and severity during the 1st week after surgery. J Am Coll Cardiol. 1991;17851- 857
PubMed

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