Nervous system

The Central Nervous System

• The weight of the brain decreases significantly with normal aging
• Blood flow to the brain decreases 20%, and significant decrements in cerebral autoregulation occur
• The age-related loss of neurons is not diffuse, and the most prominent losses tend to occur in the largest neurons. In the subcortical regions the locus ceruleus and substantia nigra appear to have large losses
• In general, the density of dendritic connections of the remaining cortical neurons is decreased. In some areas, however, the dendritic connections may increase, perhaps as a result of chronic repatterning of the brain, invoked to compensate for cellular dropout. Neurons continue to form new synapses throughout the life span
• Lipofuscin appears to accumulate in certain areas of the brain, particularly in the hippocampus and frontal cortex, but the impact of lipofuscin on function is unknown
• Myelin decreases, notably in the cortical white matter
• Changes in brain enzymes, receptors, and neurotransmitters occur. These do not imply that changes in electrophysiology, thinking, or behavior occur. On the electroencephalogram, the age changes are increases in beta waves and decreases in delta and theta waves
• Non-neurotransmitter enzymes decrease. For example, carbonic anhydrase, an important enzyme in detoxifying carbon dioxide, decreases with aging
• Neurofibrillary tangles and senile plaques occur in certain areas of the brain in normal aging, but to a much smaller extent than in Alzheimer' s disease
• Antibodies to paired helical filaments have identified nonamyloid plaques in Alzheimer's brains but not those of normal aged individuals. If this finding holds true, these lesions will clearly separate normal aging from Alzheimer's disease.
• Spinal cord motor neurons are retained in large part to age 60. However, significant losses then seem to occur in the anterior horn cells
• Finger and toe vibratory and tactile threshold decreases with age
• Finger thermal threshold appears to increase with age.

• Affect the older person's ability to distinguish between different stimuli
• Reduce reaction time, resulting possibly in injuries and burns
• Make loss of balance and falls more likely.

Vision
With age, a number of changes occur in the eye anatomy:

• The periorbital tissues atrophy; the eyelids are more relaxed
• Flaccidity of the lower lid may lead to ectropion (turns outward) or entropion (turns inward)
• Lacrimal gland function, tear production, and goblet cell function all decrease. Despite decreased tear production, atrophy leads to displacement of the lacrimal punctum by periorbital tissue, with decreased drainage and a watering eye
• The conjunctiva atrophies and yellows
• Corneal sensitivity to touch declines by 50% in advanced age
• The iris becomes more rigid, yielding a smaller, more sluggishly responsive pupil
• The lens yellows because of photo-oxidation of tryptophan in lens protein and an increased accumulation of insoluble protein in the center with the lens fibers. The yellow color causes decreased transparency to blue light
• Aqueous humor production decreases and the vitreous humor and body also shrink. Separation between the liquid and solid components may be manifest to the person as flashes of light
• The retina becomes thinner because of a loss of neurons
• Presbyopia starts insidiously in the fourth decade - the distance needed to focus near objects increases, because of the decreased lens elasticity and atrophy of the ciliary muscle
• A gradual and steady decline in static acuity (i.e. examining an object at rest) and a more pronounced loss of dynamic visual acuity (i.e. viewing objects in motion) proceeds with aging
• One of the most marked and reproducible changes in vision is that of light adaptation. The older eye adapts more slowly to light change because the pupil is rigid and the lens is more opaque. In fact, a nomogram can use dark adaptation time to predict age within 2 or 3 years
• Alterations in the lens lead to significant increases in light scattering, which makes the older person much more sensitive to glare. After cataract removal, the glare threshold becomes normal
• Because of a decline in contrast sensitivity, older persons need increased contrast to discriminate between target and background. This factor should be taken into account in the design of living environments.

• The external auditory canal atrophies; its walls thin
• Cerumen becomes drier and more tenacious, and thus has a greater tendency to form an impaction
• The tympanic membrane becomes thicker and looks duller and whiter than in a younger person
• The ossicles undergo degenerative changes in all the ossicular joints. However, sound transmission is remarkably preserved.

• Loss of hair cells in the organ of Corti
• Loss of cochlear neurons
• Stiffening of the basilar membrane and calcification of the auditory mechanisms
• Thickening of the capillaries of the stria vascularis, which is the source of endolymph
• Degeneration of spiral ligament.

Taste and Smell
There may be decreased enjoyment of food and an age-related difficulty in sorting the tastes of mixed or combined foods:

• The number of lingual papillae decrease with aging, but neurophysiologic responses are unaltered
• The acuity of olfaction declines, and since taste is a combination of gustatory sense and smell, detection thresholds are increased by 50% by age 80, and recognition of familiar smells decreases by 15%.

Cardiovascular system

Cardiovascular changes with age

• The cardiac inotropic and chronotropic maximal and submaximal responses to catecholamine stimulation and to sympathetic nervous system stimulation are markedly impaired in the older person
• The maximum heart rate declines with age. The formula, 220 minus age, estimates maximum heart rate in men; for women, 190 minus (0.8 x age) has been used
• Older and younger persons require about the same cardiac output to perform a given level of work. However, the Starling curve (i.e. increasing diastolic pressures to increase contraction) appears to be utilized much earlier to increase cardiac output in older than in younger persons. Recovery after exertion is markedly prolonged in the older person
• The heart rate response to a stimulatory maneuver like hand-grip is decreased with age.

Respiratory system

Age-related anatomic and functional changes in the respiratory system contribute to the increased frequency of infection, increased likelihood of hypoxia, and decreased maximum oxygen utilization in the older person:

• Alveolar ducts enlarge due to loss of elastic tissue, resulting in a decreased surface area for gas exchange
• Airways in dependent portions of the lung sac close at higher volumes, so that more airways are closed during all or part of the respiratory cycle. The lower portions of the lung are better perfused at all ages, but higher closing volume with age increases ventilation perfusion mismatch and accounts for declining pO2 (oxygen pressure) with age. This effect is more marked in the supine than sitting position because of changes in thoracic mechanics
• Costochondral cartilage becomes calcified, and intercostal muscle contraction accounts for less chest expansion. By age 65, inspiration normally depends on abdominal muscles, which are only partially effective in opening airways in the seated or supine position. Full airway expansion occurs only in the upright (standing) position. While alveoli are not fully expanded, they continue to be perfused. Continued perfusion extracts alveolar gases, which produces alveolar collapse and atelectasis
• Cough is less vigorous, and the greater closing volume means that the cough is unable to clear certain portions of the lungs
• Mucociliary clearance is slower and less effective. Increases in albumin, IgA, IgG, and neutrophils occur in the alveolar washings from bronchoalveolar lavage of healthy older persons; conversely, the number of bronchoalveolar macrophages appears to decrease
• Pulmonary functional reserves diminish. Pulmonary function peaks at age 30, and this peak determines the likelihood of compromise from age-related changes. In nonsmoking men, forced vital capacity (FVC) decreases between 0.15 and 0.3 liters per decade. Forced expiratory volume in 1 second (FEV1) decreases by 0.2 to 0.3 liters per decade in nonsmoking men. In women, changes are smaller and more gradual
• Total lung capacity (proportional to height) does not change significantly with age; however, the residual volume increases because of higher closing volume
• Control of ventilation is modestly compromised, with decreased responses to hypoxemia, hypercapnia, and mechanical loading, such as breathing through a small-diameter endotracheal tube. With exercise training, many of these changes normalize; the implication is that central or peripheral receptor hyporesponsiveness is due to deconditioning, not an intrinsic change with aging.

Gastrointestinal System

• The epithelium lining the oral mucosa thins
• The gums recede, exposing the tooth cementum, which is more prone to decay, and predisposing older persons to root caries
• Enamel and dentine wear down, but the teeth maintain integrity in the absence of dental caries
• There is a small decrease in the number of acinar cells of the salivary glands
• The parotid salivary glands have subtle decreases of saliva, but accessory salivary gland production is unchanged
• The older person chews food less effectively, even with intact teeth. As a result, older people keep food in the mouth longer, and they swallow larger pieces. Swallowing is less coordinated, which increases the risk of aspiration, especially when using dentures
• Anatomic changes in the esophagus include hypertrophy of the skeletal muscle at the upper third, thickening of the smooth-muscle layer along the lower two-thirds, and a decrease in numbers of the myenteric ganglion cells that coordinate peristalsis
• The amplitude of esophageal contractions during peristalsis decreases, but the movement of food is not impaired. The onset, speed, and duration of primary esophageal contractions are preserved, while secondary esophageal contractions appear to be greatly reduced. The abnormal peristalsis after swallowing, and the nonperistaltic repetitive contractions that were at one time attributed to old age, are now thought to be due to disease processes
• Altered prostaglandin synthesis of the stomach may increase the risk of gastritis
• Gastric motility is minimally altered
• Adaptive relaxation, that is, the dilation of the stomach that occurs to accept the food bolus from the esophagus, is impaired
• The small intestine undergoes modest anatomic changes, including moderate villus atrophy and coarser-appearing mucosae. Some myenteric neurons are lost, and immunologic lymphoid tissue decreases
• The duodenum appears to have the same decrease in prostaglandin synthesis as the stomach
• Functional changes in the small intestine include impaired motility in response to a food bolus
• The absorption of calcium, iron, lactose, xylose, and vitamin D is decreased
• Lactase levels decline, leading to intolerance of dairy products by many older people
• The efficiency of calcium absorption from the gut lumen decreases because of decreased vitamin D receptors in the gut and decreased levels of circulating 1,25(OH)D. Calcium and iron may also be less well absorbed. However, absorption of some highly lipid soluble compounds (vitamin A, vitamin K, and cholesterol) is faster in the older person
• Functional changes in the large intestine include slowed transit, altered coordination of contraction, and an increase in opioid receptors that may predispose the older person to drug-induced constipation
• The mass of the liver decreases, and hepatic blood flow decreases by 10% per decade
• The proximal common bile duct becomes dilated, and the preampullary common bile duct becomes narrowed
• Mild ductal proliferation and cellular accumulation of lipofuscin both occur
• The hepatocyte number decreases, while individual hepatocytes enlarge and change in morphology
• Synthesis of vitamin-K-dependent clotting factors is decreased
• Although the function and anatomy of the gall bladder are well preserved in old age, the bile composition has a higher lithogenic index, which predisposes the older person to cholesterol gall-stone formation.

Renal system

Despite major changes in the anatomy and function of the kidney with age, the renal system maintains fluid and electrolyte homeostasis remarkably well unless it is challenged:

• From 30-80 years, renal mass decreases by 25-30%, and fat and fibrosis, in part replace the functional parenchyma; thus, the decrease in renal mass actually underestimates the loss in functional tissue
• The loss in the renal cortex is most prominent, and the nephrons with the longest loops, the ones able to maximally concentrate urine, are preferentially lost
• Diffuse sclerosis of glomeruli proceeds at such a rate that 30% are destroyed by age 75. In the remaining glomeruli there is a loss of capillary loops, a decrease in epithelial cells, and an increase in mesangial cells. The filtering surface is reduced
• The basement membrane is thickened because of a hydroxylation of amino acids and an increase in the sugar content
• The renal pyramids are characterized by interstitial fibrosis
• Overall, the number and length of collecting tubules decreases, and these tubules develop diverticula
• Intrarenal vascular changes include a spiraling of the afferent arterioles and a decrease in the size of the efferent and arcuate arteries.

The functional implications of these anatomic changes mean that:

• Both cross-sectional and longitudinal studies demonstrate that populations have significant linear decreases in creatinine clearance with age (7.5 to 10 mL per minute per decade). However, there is wide variability among older individuals
• Over intervals from 15 to 20 years, some persons ( < 5%) have increases in their glomerular filtration rate (GFR). About one third have no change at all, one third have a slight decline, and one third have a more marked decline
• Urine acidification is reduced
• Excretion of an acid load is impaired
• The ability to maximally dilute urine and excrete a water load is impaired
• Because of reductions in tubular transport and the number of tubules, the older kidney is also impaired in its ability to retain amino acids and glucose. The glucose threshold of the older kidney is therefore lower
• The renin-angiotensin system is down-regulated such that there is a decreased renin response to volume depletion or salt restriction. Baseline renin activity decreases with age to a level one third of that of young adults. Atrial natriuretic peptide (ANP) increases with age, further suppressing aldosterone release. However, the effect of angiotensin-converting enzyme inhibition on renal blood flow is preserved
• One of the hormonal functions of the kidney, the hydroxylation of vitamin D, is impaired with age
• The C-terminal fragment of parathyroid hormone is normally cleared by the kidney and may be increased if there is chronic renal failure but the circulating levels of biologically active parathyroid hormone are usually normal.

Hematopoietic function

• With increasing age, bone marrow mass decreases and bone marrow fat increases. At times of high demand, functional reserve may be limited
• The hematopoietic response to phlebotomy or hypoxia is slower and less vigorous. There may be subtle changes in the effectiveness of diphosphoglycerol in altering hemoglobin dissociation or in the hemoglobin-oxygen dissociation relationship itself
• In general, circulating macrophage function is unchanged; however, tissue macrophage function is decreased
• Though the number of platelets is unchanged with age, they have an enhanced responsiveness to a number of stimulators of thrombosis.

Endocrine system

There are many changes in the endocrine system but most are compensations for other age-related changes. Only a few will therefore be considered here:

• Older people have low IGF-1 levels, and this may be due to lack of stimulation by growth hormone. IGF-1 is also decreased by physical inactivity
• The release of insulin by the older pancreas is impaired under hyperglycemic conditions. Plasma insulin levels are elevated with increasing age, possibly because of a decrease in insulin clearance
• Peripheral tissues in general are less responsive to insulin. This lowered response is likely due to decreased insulin sensitivity. In young persons growth-hormone-stimulated insulin-like growth factor 1 (IGF-1) plays the role of alternative agonist at the insulin receptors, but IGF-1 and the IGF receptor are decreased with aging. Thus, the sum effect of IGF-1 and insulin on glucose utilization is decreased
• Serum atrial natriuretic peptide (ANP) levels increase, and renal responsiveness to ANP decreases, whereas the hypotensive response to infused ANP is greater.

Reproductive system

Changes in women
There are significant anatomic changes in the ovary, the uterus, the vagina, and the breast with age:

• Estrogen production is markedly reduced; progesterone production is also reduced. Testosterone and androstenedione production are reduced, as is the conversion by the ovary of adrenal androgens to testosterone and estrone
• Both the uterus and vagina atrophy
• Vaginal secretions are reduced, the pH increases, the microbial flora is altered, and vaginal lubrication is reduced both at baseline and during intercourse
• In the breast, involution of glandular stromal and ductal tissue occurs as a result of estrogen deficiency. The acinar basement membrane is thicker, the lumina of the ducts are smaller, with cystic changes along the ducts, and fat tissue increases. The ligamentous support of the breast relaxes, and a loss of muscular tone results in an alteration in the breast contour.

Changes in Men

• A gradual decline in male reproductive ability occurs; however, men do not have the total loss of reproductive ability that occurs in women
• Sperm production decreases, and the sperm from older testes have an increased frequency of chromosomal abnormalities
• The seminiferous tubules degenerate. More Sertoli cells are multinucleated, and fewer Leydig cells are seen
• The amount of total, free, and bioavailable testosterone decreases. Because sex-hormone-binding globulin increases with age, the proportion of testosterone that is free decreases linearly with aging, probably as a consequence of a partial testicular failure
• Benign prostatic hyperplasia is present in about 90% of men by age 85. It is not clear whether this is a disease or an age-related change
• Functionally, the volume of prostate secretions in ejaculate and in urine decreases.

Skin

Normal aging changes are separate from those due to exposure to the sun (i.e. photoaging):

• An increase in the time taken for cellular renewal and a decrease in the moisture content of the stratum corneum - resulting in dry skin (xerosis)
• A 10-20% reduction in melanocytes per decade
• A 25-40% reduction in the immunologically active Langerhans' cells
• Thinning of the dermis by 20%
• A 50% reduction in nail growth
• Reduction in sweat and sebaceous gland activity.

Photoaging is the product of chronic sun exposure. Photoaging, not physiologic aging, produces 90% of the cosmetically undesirable changes in skin:

• Cellular dysplasia
• Atypical cells
• A loss of polarity of the keratinocytes
• A significant disorganization in the epidermis
• Marked elastosis in the dermis
• Aggregates of amorphous elastic fibers in the dermis
• A decrease in collagen content of the dermis
• An increase in glycosaminoglycans in the dermis
• A modest inflammatory infiltrate localized to the perivascular areas of the dermis.

Photoaged skin:

• Has a higher tendency to telangiectasias
• Is spottily hyperpigmented and hypopigmented.

Bones and muscles

See Osteoporosis section on this site for details about changes in bones with age.

• Overall, from age 30 to age 80, muscle mass decreases in relation to body weight by about 30-40%. The loss is not linear; it accelerates with increasing age
• Strength also decreases, though this loss is more modest when the loss in muscle mass is taken into account. From age 30 to age 80 a person's strength of grip decreases 60%. However, activity plays an important mitigating role: assembly line workers who used their grip over their working life do not appear to lose any strength. Overall, lower-extremity strength is lost at a relatively faster rate than upper-extremity strength
• Innervation of muscle also appears to be altered; the number of motor units in any given muscle is lower, resulting in increased motor unit size
• Though synaptic remodeling appears to occur at all ages, the stability of neuromuscular innervation is decreased with aging and synapses are eliminated. The extent and stability of any compensatory changes also decrease with age
• Contraction of muscle is altered. Examination of ankle dorsiflexion reveals a slower time to peak tension and a slower relaxation
• Skeletal muscle from older adults shows altered energetics. The decrease in enzyme activity of glycolytic enzymes is greater than that of oxidative enzymes. However, exercise or other physical activity plays a significant role in the decrease in these enzyme activities
• The diaphragm appears to be relatively resistant to these aging changes, underscoring the mitigating effect of activity
• With age, water content decreases in tendons and ligaments, and stiffness increases
• Body collagen turnover, and thus the rate of remodeling of the tendon and ligament, decreases with age.
• Tensile strength of articular cartilage decreases, and there are marked biochemical changes in the composition of cartilage
• There is an increase in hyaluronic acid in cartilage, but a decrease in synovial fluid.

Physiological rhythms

The most consistent age-associated changes in physiological rhythms are:

• A reduction in circadian amplitude of such physiologic processes as body temperature, plasma cortisol, and sleep
• Desynchronization among different rhythms or "internal phase drift"
• A phase advance in some rhythms such that the 24-hour body temperature trough and sleep onset occur 1 to 2 hours earlier in older adults
• Delay in the ability to re-entrain physiologic rhythms to a new photoperiod
• Age-associated attenuations occur in pulsatile secretions of gonadotropins, growth hormone, thyrotropin, melatonin, and adrenocorticotropic hormone (ACTH). Although some of these changes may represent biomarkers of aging, their functional significance is not known
• Heart-rate variability, blood-pressure variability, electroencephalographic frequencies, auditory frequencies, postural sway, and physiologic tremor all demonstrate a loss of high-frequency variability with age. This has been called a "loss of spectral reserve" and indicates a loss of complexity, a concept derived from the field of nonlinear dynamics. This loss of complexity may be a general principle of all aging systems and may contribute to the attenuated responsiveness to stressors.

Homeostasis

Many of the most pronounced changes with aging are impaired responses to external stimuli. They are more apparent when a person is challenged, since older persons either:

• Have limited physiologic reserves with which to maintain the internal physiologic milieu
• Already employ some of their physiologic reserves just to maintain baseline homeostasis. They therefore have less remaining for external challenges.

• Alpha-adrenergic receptor responsiveness appears to be preserved with age, while beta-receptor responsiveness appears to decrease in most systems
• In the MacArthur studies of successful aging, healthy older persons with higher systolic blood pressure, higher overnight cortisol and catecholamine secretion, and other evidence of activation of stress responses, were more likely to have declines in cognitive or physical function during 3 years of follow-up.

Blood pressure regulation
Older patients, especially those with hypertension, are at higher risk for orthostatic hypotension:

• There may be changes in the cerebral vascular system that constrict the limits of autoregulation of perfusion, narrowing the range of blood pressure within which the central nervous system perfusion can be maintained. When the brain is underperfused, falls or syncope may result
• Beta-adrenergic-mediated vasodilation appears to be significantly impaired with age in the arterial tree but only modestly decreased in veins, and alpha-adrenergic vasoconstriction is unaltered.

Thermoregulation
Older people have an increased susceptibility to hypothermia. They have:

• Less heat production per kilogram of body weight, though this age effect is smaller when corrections for lean body mass, which decreases with aging, are made
• Reduced muscle activity and less efficient shivering
• Reduced meal- or glucose-induced thermogenesis
• Impaired vasoconstrictor response to cooling by the skin arterioles, thus impeding ability to conserve heat
• Difficulty in discriminating temperature differences and often a delayed perception of being cold, in comparison with younger people.

• Their skin vasodilatation response is impaired
• Greater threshold temperature is required to initiate sweating
• Decreased sweat production occurs, both in response to heating and in response to cholinergic agonists.

Volume regulation
Older people are at higher risk of volume depletion:

• Basal levels of antidiuretic hormone (ADH) are somewhat increased with age, yet basal serum sodium and basal osmolality are unchanged
• Reserves of body water are decreased because water constitutes a decreasing percentage of body mass with increasing age
• Central nervous system regulation of body fluids status is altered with aging. The older person has a decreased thirst drive, which may be mediated by decreased endogenous opioids (endorphins) or decreased responsiveness to them
• Maximum urine osmolality decreases and achievement of the maximally concentrated urine is delayed; thus, the volume of water excreted in the urine during water deprivation is higher
• The kidney's responsiveness to the renin-angiotensin-aldosterone pathway and atrial natriuretic peptide is impaired
• The number of very long nephrons that maximally concentrate urine decreases, and the interstitium around the loops of these long nephrons has a somewhat lower tonicity, which contributes to the propensity of the older person to develop dehydration
• It is much more difficult for older persons to excrete a fluid load, which also predisposes them to hyponatremia or even congestive heart failure.