Senescence of the Organ Systems

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Organ systems do not all degenerate at the same rate. For example, from ages 30 to 80, the speed of nerve conduction declines only 10% to 15%, but the number of functional glomeruli in the kidneys declines about 60%. Some physiological functions show only moderate changes at rest but more pronounced differences when tested under exercise conditions. The organ systems also vary widely in the age at which senescence becomes noticeable. There are traces of atherosclerosis, for example, even in infants, and visual and auditory sensitivity begin to decline soon after puberty. By contrast, the female reproductive system does not show significant senescence until menopause and then its decline is relatively abrupt. Aside from these unusual examples, most physiological measures of performance peak between the late teens and age 30 and then decline at a rate influenced by the level of use of the organs.

Integumentary System

Two-thirds of people aged 50 and over, and nearly all people over age 70, have medical concerns or complaints about their skin. Senescence of the integumentary system often becomes most noticeable in the late 40s. The hair turns grayer and thinner as melanocytes die out, mitosis slows down, and dead hairs are not replaced. The atrophy of sebaceous glands leaves the skin and hair drier. As epidermal mitosis declines and collagen is lost from the der-

mis, the skin becomes almost paper-thin and translucent. It becomes looser because of a loss of elastic fibers and flattening of the dermal papillae, which normally form a stress-resistant corrugated boundary between the dermis and epidermis. If you pinch a fold of skin on the back of a child's hand, it quickly springs back when you let go; do the same on an older person and the skinfold remains longer. Because of its loss of elasticity, aged skin sags to various degrees and may hang loosely from the arm and other places.

Aged skin has fewer blood vessels than younger skin, and those that remain are more fragile. The skin can become reddened as broken vessels leak into the connective tissue. Many older people exhibit rosacea—patchy networks of tiny, dilated blood vessels visible especially on the nose and cheeks. Because of the fragility of the dermal blood vessels, aged skin bruises more easily. Injuries to the skin are more common and severe in old age, partly because the cutaneous nerve endings decline by two-thirds from age 20 to 80, leaving one less aware of touch, pressure, and injurious stimuli. Injured skin heals slowly in old age because of poorer circulation and a relative scarcity of immune cells and fibroblasts. Antigen-presenting dendritic cells decline by as much as 40% in the aged epidermis, leaving the skin more susceptible to recurring infections.

Thermoregulation is a serious problem in old age because of the atrophy of cutaneous blood vessels, sweat glands, and subcutaneous fat. Older people are more vulnerable to hypothermia in cold weather and heatstroke in hot weather. Heat waves and cold spells take an especially heavy toll among the elderly poor, who suffer from a combination of reduced homeostasis and inadequate housing.

These are all "normal" changes in the skin, or intrinsic aging—changes that occur more or less inevitably with the passage of time. In addition, there is photoaging— degenerative changes in proportion to a person's lifetime exposure to ultraviolet radiation. UV radiation accounts for more than 90% of the integumentary changes that people find medically troubling or cosmetically disagreeable: skin cancer; yellowing and mottling of the skin; age spots, which resemble enlarged freckles on the back of the hand and other sun-exposed areas; and wrinkling, which affects the face, hands, and arms more than areas of the body that receive less exposure. A lifetime of outdoor activity can give the skin a leathery, deeply wrinkled, "outdoorsy" appearance (fig. 29.17), but beneath this rugged exterior is a less happy histological appearance. The sun-damaged skin shows many malignant and premalignant cells, extensive damage to the dermal blood vessels, and dense masses of coarse, frayed elastic fibers underlying the surface wrinkles and creases.

Senescence of the skin has far-reaching effects on other organ systems. Cutaneous vitamin D production declines as much as 75% in old age. This is all the more

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Senescence Saladin

Figure 29.17 Senescence of the Skin. The skin exhibits both intrinsic aging and photoaging. The deep creases seen here result mainly from photoaging.

Photograph of child from The 1974 Science Year. 1973 Field Enterprises Educational Corporation. By permission of World Book, Inc.

Figure 29.17 Senescence of the Skin. The skin exhibits both intrinsic aging and photoaging. The deep creases seen here result mainly from photoaging.

Photograph of child from The 1974 Science Year. 1973 Field Enterprises Educational Corporation. By permission of World Book, Inc.

significant because the elderly spend less time outdoors, and because of increasing lactose intolerance, they often avoid dairy products, the only dietary source of vitamin D. Consequently, the elderly are at high risk of calcium deficiency, which, in turn, contributes to bone loss, muscle weakness, and impaired glandular secretion and synaptic transmission.

Skeletal System

After age 30, osteoblasts become less active than osteoclasts. This imbalance results in osteopenia, the loss of bone; when the loss is severe enough to compromise a person's physical activity and health, it is called osteoporosis (see p. 239). After age 40, women lose about 8% of their bone mass per decade and men about 3%. Bone loss from the jaws is a contributing factor in tooth loss.

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Not only does bone density decline with age, but the bones become more brittle as the cells synthesize less protein. Fractures occur more easily and heal more slowly. A fracture may impose a long period of immobility, which makes a person more vulnerable to pneumonia and other infectious diseases.

People notice more stiffness and pain in the synovial joints as they age, and degenerative joint diseases affect the lifestyle of 85% of people over age 75. Synovial fluid is less abundant and the articular cartilage is thinner or absent. Exposed bone surfaces abrade each other and cause friction, pain, and reduced mobility. Osteoarthritis is the most common joint disease of older people and one of the most common causes of physical disability (p. 320). Even breathing becomes more difficult and tiring in old age because expansion of the thorax is restricted by calcification of the sternocostal joints. Degeneration of the intervertebral discs causes back pain and stiffness, but herniated discs are less common in old age than in youth because the discs become more fibrous and stronger, with less nucleus pulposus.

Muscular System

One of the most noticeable changes we experience with age is the replacement of lean body mass (muscle) with fat. The change is dramatically exemplified by CT scans of the thigh. In a young well-conditioned male, muscle accounts for 90% of the cross-sectional area of the midthigh, whereas in a frail 90-year-old woman, it is only 30%. Muscular strength and mass peak in the 20s; by the age of 80, most people have only half as much strength and endurance. A large percentage of people over age 75 cannot lift a 4.5 kg (10 lb) weight with their arms; such simple tasks as carrying a sack of groceries into the house may become impossible. The loss of strength is a major contributor to falls, fractures, and dependence on others for the routine activities of daily living. Fast-twitch fibers exhibit the earliest and most severe atrophy, thus increasing reaction time and reducing coordination.

There are multiple reasons for the loss of strength. Aged muscle fibers have fewer myofibrils, so they are smaller and weaker. The sarcomeres are increasingly disorganized, and muscle mitochondria are smaller and have reduced quantities of oxidative enzymes. Aged muscle has less ATP, creatine phosphate, glycogen, and myoglobin; consequently, it fatigues quickly. Muscles also exhibit more fat and fibrosis with age, which limits their movement and blood circulation. With reduced circulation, muscle injuries heal more slowly and with more scar tissue.

But the weakness and easy fatigue of aged muscle also stems from the senescence of other organ systems. There are fewer motor neurons in the spinal cord, and some muscle shrinkage may represent denervation atrophy. The remaining neurons produce less acetylcholine and show less efficient synaptic transmission, which makes

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1110 Part Five Reproduction and Development the muscles slower to respond to stimulation. As muscle atrophies, motor units have fewer muscle fibers per motor neuron, and more motor units must be recruited to perform a given task. Tasks that used to be easy, such as buttoning the clothes or eating a meal, take more time and effort. The sympathetic nervous system is also less efficient in old age; consequently, blood flow to the muscles does not respond efficiently to exercise and this contributes to their rapid fatigue.

Nervous System

The nervous system reaches its peak development around age 30. The average brain weighs 56% less at age 75 than at age 30. The cerebral gyri are narrower, the sulci are wider, the cortex is thinner, and there is more space between the brain and meninges. The remaining cortical neurons have fewer synapses, and for multiple reasons, synaptic transmission is less efficient: The neurons produce less neuro-transmitter, they have fewer receptors, and the neuroglia around the synapses is more leaky and allows neurotrans-mitter to diffuse away. The degeneration of myelin sheaths with age also slows down signal conduction.

Neurons exhibit less rough ER and Golgi complex with age, which indicates that their metabolism is slowing down. Old neurons accumulate lipofuscin pigment and show more neurofibrillary tangles—dense mats of cytoskeletal elements in their cytoplasm. In the extracellular material, plaques of fibrillar protein (amyloid) appear, especially in people with Down syndrome and Alzheimer disease (AD). AD is the most common nervous disability of old age (p. 475).

Not all functions of the central nervous system are equally affected by senescence. Motor coordination, intellectual function, and short-term memory decline more than language skills and long-term memory. Elderly people are often better at remembering things in the distant past than remembering recent events.

The sympathetic nervous system loses adrenergic receptors with age and becomes less sensitive to norepi-nephrine. This contributes to a decline in homeostatic control of such variables as body temperature and blood pressure. Many elderly people experience orthostatic hypotension—a drop in blood pressure when they stand, which sometimes results in dizziness, loss of balance, or fainting.

Sense Organs

Some sensory functions decline shortly after adolescence. Presbyopia (loss of flexibility in the lenses) makes it more difficult for the eyes to focus on nearby objects. Visual acuity declines and often requires corrective lenses by middle age. Cataracts (cloudiness of the lenses) are more common in old age. Night vision is impaired as more and more light is needed to stimulate the retina. This has several causes:

There are fewer receptor cells in the retina, the vitreous body becomes less transparent, and the pupil becomes narrower as the pupillary dilators atrophy. Dark adaptation takes longer as the enzymatic reactions of the pho-toreceptor cells become slower. Changes in the structure of the iris, ciliary body, or lens can block the reabsorption of aqueous humor, thereby increasing the risk of glaucoma. Having to give up reading and driving can be among the most difficult changes of lifestyle in old age.

Auditory sensitivity peaks in adolescence and declines afterward. The tympanic membrane and the joints between the auditory ossicles become stiffer, so vibrations are transferred less effectively to the inner ear, creating a degree of conductive deafness. Nerve deafness occurs as the number of cochlear hair cells and auditory nerve fibers declines. The greatest hearing loss occurs at high frequencies and in the frequency range of most conversation. The death of receptor cells in the semicircular ducts, utricle, and saccule, and of nerve fibers in the vestibular nerve and neurons in the cerebellum, results in poor balance and dizziness—another factor in falls and bone fractures.

The senses of taste and smell are blunted as taste buds, olfactory cells, and second-order neurons in the olfactory bulbs decline in number. Food may lose its appeal, and thus declining sensory function can be a factor in malnutrition.

Endocrine System

The endocrine system degenerates less than any other organ system. The reproductive hormones drop sharply and growth hormone and thyroid hormone secretion decline steadily after adolescence, but other hormones continue to be secreted at fairly stable levels even into old age. Target cell sensitivity declines, however, so some hormones have less effect. For example, the pituitary gland is less sensitive to negative feedback inhibition by adrenal glucocorticoids; consequently, the response to stress is more prolonged than usual. Diabetes mellitus is more common in old age, largely because target cells have fewer insulin receptors. In part, this is an effect of the greater percentage of body fat in the elderly. The more fat at any age, the less sensitive other cells are to insulin. Body fat increases as the muscles atrophy, and muscle is one of the body's most significant glucose-buffering tissues. Because of the blunted insulin response, glucose levels remain elevated longer than normal after a meal.

Circulatory System

Cardiovascular disease is a leading cause of death in old age. Senescence has multiple effects on the blood, heart, arteries, and veins. Anemia may result from nutritional deficiencies, inadequate exercise, disease, and other causes. The factors that cause anemia in older people are so complicated it is almost impossible to control them

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Physiology: The Unity of Companies, 2003 Form and Function, Third Edition enough to determine whether aging alone causes it. Evidence suggests that there is no change in the baseline rate of erythropoiesis in old age. Hemoglobin concentration, cell counts, and other variables are about the same among healthy people in their 70s as in the 30s. However, older people do not adapt well to stress on the hemopoietic system, perhaps because of the senescence of other organ systems. As the gastric mucosa atrophies, for example, it produces less of the intrinsic factor needed for vitamin B12 absorption. This increases the risk of pernicious anemia. As the kidneys age and the number of nephrons declines, less erythropoietin is secreted. There may also be a limit to how many times the hemopoietic stem cells can divide and continue giving rise to new blood cells. Whatever its cause, anemia limits the amount of oxygen that can be transported and thus contributes to the atrophy of tissues everywhere in the body.

_Think About It_

Draw a positive feedback loop showing how anemia and senescence of the kidneys could affect each other.

Everyone exhibits coronary atherosclerosis with age. Consequently, myocardial cells die, angina pectoris and myocardial infarction become more common, the heart wall becomes thinner and weaker, and stroke volume, cardiac output, and cardiac reserve decline. Like other connective tissues, the cardiac skeleton becomes less elastic. This limits the distension of the heart and reduces the force of cardiac systole. Degenerative changes in the nodes and conduction pathways of the heart lead to a higher incidence of cardiac arrhythmia and heart block. Physical endurance is compromised by the drop in cardiac output.

Arteries stiffened by atherosclerosis cannot expand as effectively to accommodate the pressure surges of cardiac systole. Blood pressure therefore rises steadily with age (see table 20.1, p. 755). Atherosclerosis also narrows the arteries and reduces the perfusion of most organs. The effects of reduced circulation on the skin, skeletal muscles, and brain have already been noted. The combination of atherosclerosis and hypertension also weakens the arteries and increases the risk of aneurysm and stroke.

Atherosclerotic plaques trigger thrombosis, especially in the lower extremities, where flow is relatively slow and the blood clots more easily. About 25% of people over age 50 experience venous blockage by thrombosis—especially people who do not exercise regularly.

Degenerative changes in the veins are most evident in the extremities. The valves become weaker and less able to stop the backflow of blood. Blood pools in the legs and feet, raises capillary blood pressure, and causes edema. Chronic stretching of the vessels often produces varicose veins and hemorrhoids. Support hose can reduce edema by compressing the tissues and forcing tissue fluid to

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return to the bloodstream, but physical activity is even more important in promoting venous return.

Immune System

The amounts of lymphatic tissue and red bone marrow decline with age; consequently there are fewer hemopoi-etic stem cells, disease-fighting leukocytes, and antigen-presenting cells (APCs). Also, the lymphocytes produced in these tissues often fail to mature and become immuno-competent. Both humoral and cellular immunity depend on APCs and helper T cells, and therefore both types of immune response are blunted. As a result, an older person is less protected against cancer and infectious diseases. It becomes especially important in old age to be vaccinated against influenza and other acute seasonal infections.

Respiratory System

Pulmonary ventilation declines steadily after the 20s and is one of several factors in the gradual loss of stamina. The costal cartilages and joints of the thoracic cage become less flexible, the lungs have less elastic tissue, and the lungs have fewer alveoli. Vital capacity, minute respiratory volume, and forced expiratory volume fall. The elderly are also less capable of clearing the lungs of irritants and pathogens and are therefore increasingly vulnerable to respiratory infections. Pneumonia causes more deaths than any other infectious disease and is often contracted in hospitals and nursing homes.

The chronic obstructive pulmonary diseases (COPDs)— emphysema and chronic bronchitis—are more common in old age since they represent the cumulative effects of a lifetime of degenerative change. They are among the leading causes of death in old age. Pulmonary obstruction also contributes to cardiovascular disease, hypoxemia, and hypoxic degeneration in all the organ systems. Respiratory health is therefore a major concern in aging.

Urinary System

The kidneys exhibit a striking degree of atrophy with age. From ages 25 to 85, the number of nephrons declines 30% to 40% and up to a third of the remaining glomeruli become atherosclerotic, bloodless, and nonfunctional. The kidneys of a 90-year-old are 20% to 40% smaller than those of a 30-year-old and receive only half as much blood. The glomerular filtration rate is proportionately lower and the kidneys are less efficient at clearing wastes from the blood. Although baseline renal function is adequate even in old age, there is little reserve capacity; thus other diseases can lead to surprisingly rapid renal failure. Drug doses often need to be reduced in old age because the kidneys cannot clear drugs from the blood as rapidly; this is a contributing factor in overmedication among the aged.

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Water balance becomes more precarious in old age because the kidneys are less responsive to antidiuretic hormone and because the sense of thirst is sharply reduced. Even when given free access to water, elderly people may not drink enough to maintain normal blood osmolarity. Dehydration is therefore common. It is often said that aged kidneys are deficient in maintaining electrolyte balance, but the evidence for this remains questionable.

Voiding and bladder control become a problem for both men and women. About 80% of men over the age of 80 are affected by benign prostatic hyperplasia. The enlarged prostate compresses the urethra and interferes with emptying of the bladder. Urine retention causes pressure to back up in the kidneys, aggravating the failure of the nephrons. Older women are subject to incontinence (leakage of urine), especially if their history of pregnancy and childbearing has weakened the pelvic muscles and urethral sphincters. Senescence of the sympathetic nervous system and nervous disorders such as stroke and Alzheimer disease can also cause incontinence.

Digestive System and Nutrition

Less saliva is secreted in old age, making food less flavorful, swallowing more difficult, and the teeth more prone to caries. Nearly half of people over age 65 wear dentures because they have lost their teeth to caries and periodon-titis. The stratified squamous epithelium of the oral cavity and esophagus is thinner and more vulnerable to abrasion.

The gastric mucosa atrophies and secretes less acid and intrinsic factor. Acid deficiency reduces the absorption of calcium, iron, zinc, and folic acid. Heartburn becomes more common as the weakening lower esophageal sphincter fails to prevent reflux into the esophagus. The most common digestive complaint of older people is constipation, which results from the reduced muscle tone and weaker peristalsis of the colon. This seems to stem from a combination of factors: atrophy of the muscularis externa, reduced sensitivity to neurotransmitters, less fiber and water in the diet, and less exercise. The liver, gallbladder, and pancreas show only slightly reduced function. Any drop in liver function, however, makes it harder to detoxify drugs and can contribute to overmedication.

Older people tend to reduce their food intake because of lower energy demand and appetite, because declining sensory functions make food less appealing, and because reduced mobility makes it more troublesome to shop and prepare meals. However, they need fewer calories than younger people because they have lower basal metabolic rates and tend to be less physically active. Protein, vitamin, and mineral requirements remain essentially unchanged, although vitamin and mineral supplements may be needed to compensate for reduced food intake and intestinal absorption. Malnutrition is common among older people and is an important factor in anemia and reduced immunity.

Reproductive System

In men, the senescent changes in the reproductive system are relatively gradual; they include declining testosterone secretion, sperm count, and libido. By age 65, sperm count is about one-third of what it was in a man's 20s. Men remain fertile (capable of fathering a child) well into old age, but impotence (inability to maintain an erection) can occur because of atherosclerosis, hypertension, medication, and psychological reasons.

In women, the changes are more pronounced and develop more rapidly, over the course of menopause. The ovarian follicles are used up, gametogenesis ceases, and the ovaries stop producing sex steroids. This may result in vaginal dryness, genital atrophy, and reduced libido and make sex less enjoyable. With the loss of ovarian steroids, a postmenopausal woman has an elevated risk of osteoporosis and atherosclerosis.

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Responses

  • Alanna
    Which organ systems exhibit the most senescence?
    8 years ago
  • caramella
    Which organ exhibits the most senescence?
    5 years ago

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