CHANGES ASSOCIATED WITH NORMAL AGING We have already noted the critical and difficult distinction a clinician must

make to attribute a finding to either the expected course of aging or the result of pathologic changes. This distinction perplexes the researcher as well. We currently lack precise knowledge of what constitutes normal aging. Much of our information comes from cross-sectional studies, which compare findings from a group of younger persons with those from a group of older individuals. Such data may reflect differences other than simply the effects of age. The older group grew up in a different environment, perhaps with different diet and activities. They represent a cohort of survivors. We have come to appreciate that what we see in the older patient is largely a result of what is brought to old age. For example, the decrease in the frequency of osteoporosis today has been related to the observation that women entering the high-risk period (postmenopause) have stronger bones with thicker cortices. Many of the changes associated with aging result from gradual loss. These losses may often begin in early adulthood, butthanks to the redundancy of most organ systemsthe decrement does not become functionally significant until the loss is fairly extensive. Based on cross-sectional comparisons of groups at different ages, most organ systems seem to lose function at about 1 percent a year beginning around age 30 years. Other data suggest that the changes in people followed longitudinally are much less dramatic and certainly begin well after age 70 years. In some organ systems, such as the kidney, a subgroup of persons appear to experience gradually declining function over time, whereas others' function remains constant. These findings suggest that the earlier theory of gradual loss must be reassessed as reflecting disease rather than aging. Given a pattern of gradual deteriorationwhether from aging or disease or bothwe are best advised to think in terms of thresholds. The loss of function does not become significant until it crosses a given level. Thus the functional performance of an organ in an older person depends on two principal factors: (1) the rate of deterioration and (2) the level of performance needed. It is not surprising then to learn that most older persons will have normal laboratory values. The critical differencein fact, the hallmark of aginglies not in the resting level of performance but in how the organ (or organism) adapts to external stress. For example, an older person may have a normal fasting blood sugar but be unable to handle a glucose load within the normal parameters for younger subjects. The same pattern of decreased response to stress can be seen in the performance of other endocrine systems or the cardiovascular system. An older individual may have a normal resting pulse and cardiac output but be unable to achieve an adequate increase in either with exercise. Sometimes the changes of aging work together to produce apparently normal resting values in other ways. For example, although both glomerular filtration and renal blood flow decrease with age, many elderly persons have normal serum creatinine levels because of the concomitant decreases in lean muscle mass and creatinine production. Thus serum creatinine is not as good an indicator of renal function in the elderly as in younger persons. Because knowledge of kidney function is so critical in drug therapy, it is important to get some measure of this parameter. A useful formula for estimating creatinine clearance on the basis of serum creatinine values in the elderly has been developed (Cockcroft and Gault, 1976). (The actual formula is provided in Chap. 14.) Table 1-1 summarizes some of the pertinent changes that occur with aging. For many items, the changes begin in adulthood and proceed gradually; others may not manifest themselves until well into seniority. Readers interested in a more detailed discussion of the changes associated

with aging should consult the several excellent reviews on the subject (Birren and Schaie, 2001; Masoro and Austad, 2001). TABLE 1-1 CHANGES ASSOCIATED WITH AGING ITEM MORPHOLOGY FUNCTION Overall Decreased height (vertebral compression and stooped posture secondary to increased kyphosis) Decreased weight (after age 80 in longitudinal studies) Increased fat-to-lean body mass ratio Decreased total body water Skin Increased wrinkling Atrophy of sweat glands Cardiovascular Elongation and tortuosity of arteries, Decreased cardiac output system including aorta during exercise Increased intimal thickening of arteries Decreased heart rate of arteries Increased fibrosis of media of arteries response to stress Sclerosis of heart valves Decreased compliance of peripheral blood vessels Kidney Increased number of abnormal glomeruli Decreased creatinine clearance Interstitial fibrosis Decreased renal blood flow Decreased maximum urine osmolality Lung Decreased elasticity Decreased forced vital Decreased activity of cilia capacity and forced expiratory volume Decreased maximal oxygen uptake Decreased cough reflex Gastrointestinal Decreased hydrochloric acid Slowed intestinal motility tract Fewer taste buds Skeleton Osteoarthritis Loss of bone structure Eyes Arcus senilis Deceased accommodation Decreased pupil size Hyperopia Growth of lens Decreased acuity Decreased color sensitivity Decreased depth perception Hearing Degenerative changes of ossicles Decreased perception in high Increased obstruction of eustachian tube frequencies Atrophy of external auditory meatus Decreased pitch discrimination Atrophy of cochlear hair cells Loss of auditory neurons Immune system Decreased T-cell activity Nervous system Decreased brain weight Increased motor response Decreased cortical cell count Slower psychomotor performance Decreased intellectual performance Decreased complex learning

Endocrine

Decreased hours of sleep Decreased hours of rapid eye movement (REM) sleep Decreased triiodo-thyronine (T3) Decreased free (unbound) testosterone Increased insulin Increased norepinephrine Increased parathormone Increased vasopressin