CHAPTER3 The Physiology of Age-Related and Lifestyle-Related Decin s and down to the floor. B0X3-3 oss shoul ng any basi nd,hae po eral clinical implica- Associated Clinical Consequences tions.From a biomechanical perspective,stiffness im- ysiological with Age Clinical Cor plies a lack that tran Dec ne in maximum heart Sma tendon avu than rup 5sberobicworktload within tissu Decine in Vo max Smaller aerobic workoad proportion of total tension (i.e.,total muscle tens ion as nplian the sum of active and passive tension)that can beatr vascular tissues uple t the de hat n passiv. Loss of cells from the sa node wer heart rate cular effort required for less output.Increased tissue Lower na stiffness is one factor contributing to less muscle endur actiity of the vascular walls an e with age the thre Lower Vo:max in age-related tent from the matrix,increase in number of collag d basement RedlcedarteriovenousO loss of elastic properties. Loss of elas. membrane in capillary uptake crosslinks,and ticity is ab eviden aging skin contributing to change in function.As inconceivable as it is to regard 35-year-old baseball or basketbal player as sport,age e-related change in rat con ne for an expe and muscles.internal organs are no longer held in bave a maximum heart rate (HRmax)of 140 bpm which place as well as they were,and age-related changes in obviously limits the extent of cardiovascular challenge connec that can be endur to any duration for the sl ng or ae thougb 90-vear-olds are still capable of completing Cardiovascular Tissues New York City marathon,their times are typically 7to 8 hours,which is analogous in speed to a 3 -mph wal Fundamental changes in tissues that occur 3.3. ancion.Probabhyh most hat lo term aerobic na ipation w uld stave off de- cline for approximately a decade,more recent study does ontentio B0X3-2 Major Age-Related Cha jes in ally nd Associated ,eand causes heen ide le in Clinical Consequence ess of the heart with slower filling of the left ven kage0faticaularcartiage and age sinoatr od in the is ar it is a fundamental feature of older age.which transates ase in number of ossible aerobic workload. collagen crosslinks th comit t an hine in Vo max ely 109 ne i Loss of elastic fibers Saging skin and decade s4 Thus.a healthy active 8o-vear old woman who had an HRmax of 200 bpm as a 20-year-old and a Vozmax of ~45 mL O:/kg/min now
32 CHAPTER 3 The Physiology of Age-Related and Lifestyle-Related Decline reaching into high cupboards and down to the floor. Range loss should not preclude accomplishing any basic activities—it merely reduces the potential for extremes. Stiffness, on the other hand, has several clinical implications. From a biomechanical perspective, stiffness implies a lack of “give” that translates, for example, to a greater likelihood of tendon avulsion rather than rupture.58,59 Stiffness also means that the passive tension within tissues is increased. Phrased another way, the proportion of total tension (i.e., total muscle tension as the sum of active and passive tension) that can be attributed to passive stiffness is increased with age. Couple the increase in passive “drag” with the decline in muscle force that occurs with aging, the consequence is greater muscular effort required for less output. Increased tissue stiffness is one factor contributing to less muscle endurance with age. Box 3-2 summarizes the three major age-related changes in collagenous tissues: decreased water content from the matrix, increase in number of collagen crosslinks, and loss of elastic properties. Loss of elasticity is abundantly evident in aging skin which no longer has its turgor and tends to hang. Tendons, ligaments, and muscles also lose their elasticity, further contributing to change in function. As inconceivable as it is to regard a 35-year-old baseball or basketball player as “too old” for the sport, age-related change in connective tissue is one of the major contributors to “losing one’s edge” in athletics. In addition to tendons and muscles, internal organs are no longer held in place as well as they were, and age-related changes in connective tissues contribute to the tendency for uterine prolapse, bladder issues, constipation, and hernia with advancing years. Cardiovascular Tissues Fundamental changes in vascular tissues that occur with aging, summarized in Box 3-3, have a profound effect on function. Probably the most notable and clinically important change is the decline in maximum heart rate.60-62 The typical formula of 220 minus age provides a relative guideline for an expected change in maximum heart rate. Thus, an 80-year old individual is likely to have a maximum heart rate (HRmax) of 140 bpm which obviously limits the extent of cardiovascular challenge that can be endured for any duration. One of the primary reasons for the slowing of aerobic performance with age is the reduction in maximum heart rate. Even though 90-year-olds are still capable of completing the New York City marathon, their times are typically 7 to 8 hours, which is analogous in speed to a 3-mph walk. Does participation in lifelong exercise prevent the decline in maximum heart rate? Although it was believed that long-term aerobic participation would stave off decline for approximately a decade, more recent study does not support this contention.60,61 At this juncture, scientists do not fully understand what causes the decline in maximum heart rate, although factors contributing to the process have been identified. For example, increased stiffness of the heart with slower filling of the left ventricle, is one factor,63 and age-related decrease in the number of cells in the sinoatrial (SA) node is another factor. Regardless of the cause of lower maximum HR, it is a fundamental feature of older age, which translates to lower possible aerobic workload. Coupled with the decline in maximum HR is a concomitant and related decline in V· o2max. Both decline in a collinear fashion at a rate of approximately 10% per decade.64-67 Thus, a healthy, reasonably active 80-yearold woman who had an HRmax of 200 bpm as a 20-year-old and a V· o2max of ,45 mL O2/kg/min now BOX 3-2 Major Age-Related Changes in Collagenous Tissues and Associated Clinical Consequences Age-Related Change Clinical Consequence Loss of water from the matrix Shrinkage of articular cartilage, vertebral discs Decreased ability to absorb shock Reduced range of motion Increase in number of collagen crosslinks “Stiffer” tissues, greater passive tension within tissues More effort required to move Loss of end range of motion Loss of elastic fibers Sagging skin and organs; Less “give” to tendons, ligaments, fascia. BOX 3-3 Major Age-Related Changes in Cardiovascular Tissues and Associated Clinical Consequences Anatomic/Physiological Change with Age Clinical Consequences Decline in maximum heart rate Smaller aerobic workload possible Decline in V· o2max Smaller aerobic workload possible Stiffer, less compliant vascular tissues Higher blood pressures Slower ventricle filling time with reduced cardiac output Loss of cells from the SA node Slower heart rate Lower HRmax Reduced contractility of the vascular walls Slower HR Lower V· o2max Smaller aerobic workload possible Thickened basement membrane in capillary Reduced arteriovenous O2 uptake
CHAPTER 3 The Physiology of Age-Related and Lifestyle-Related Dedine 33 -20to Perhaps of connective vascular disease howey ver,can decrease the maximum by the capillary wall thickens with ae Thus the another 50%to values as low as 10%or 15% exchange of oxygen and nutrients from the vasculature There is mas and working tissues occurs more slowly.Because tissu ave highe more e。 any age,the higher the maximal aerobic capacity.Th of exercise itating a warm than the who are sarcopenic have very low aerobic capacity. usual requisite 3 minutes prior to more rigorous work adding muscle mass to the sarcopenic in- Thic ing of the basemer in sedent not in master s th ia t traini Indeed Physical therapists regularly treat older adults who mer and womer revealed that base emer membran nts ar thic 09 ent afte nt Wheth brane thickening ccurs at older and it is quite common for patients older than ag 60 vears e 13 to Diseases of the peripher vasculature such as diabetes ange, wh anslate D)furth have faced the Geien fo challenge of the deconditioned older adult who is hospi breakdown and nonhealing of ulcers.Lack of perfusion imposing inactivity-relatec decline on a ers,and system arly run out of gh HR f capac of perfusion to ne ds to ne opath 5 ee oal in the ma related ir enormous loss in cardiovascular reserve is one maio contributor to loss in homeostasis as well as loss of inde ange. Because of th increase dence of the funda the vascula urrently a que maTh uld not be in ed to trix composition,and loss of elastin,the entire vascular gest that increased blood pres ssure is not problematic There is a substantial body of literature indicating tha stiffer and ompliant. Mos is the olood pres ures e,an n occurs wit the the mised as well,which results in a reduction of cardia who is overmedicated,hypotension can result in dizzi- ness and r falling.Changes in medica 5% c mat on a ly ind H. odif pre cated for hypertension.Rarely has the patient's medica is probably needed here as well.More clarityonwhat fundamental constitutes"normal"blood pressure for an 80-year-old pressur ascertaine while the patien sus that of a 6 year-old and a centenarian helan's It is not un accepta pr r sl tions during exercise.Consequently from the stand- patients with heart disease is not known.Also unknow point of exercise safety.the physical therapist mus is whether age affects the effectiveness of treatments for ch for blood pressure ease that hypertension high t mpera that older adults I to the discu of age-related decline i the slower arteriovenous oxvgen exchange stiffer vas. tance to physical therapy sthesia.Men and womer cular tissues,reduction in sympathetic nervous syst of all ages are affected by inhalation anesthesia.but with are most noticeable in older adult who E already lo a significant amount of cardiovascula
CHAPTER 3 The Physiology of Age-Related and Lifestyle-Related Decline 33 has a maximum HR of 140 and a V· o2max of ,20 to 25 mL O2/kg/min. The presence of vascular and cardiovascular disease, however, can decrease the maximum by another 50% to values as low as 10% or 15%. There is also a correlation between muscle mass and V · o2max, which is the primary reason men have higher max values than women.67,68 The higher the lean mass at any age, the higher the maximal aerobic capacity. Those who are sarcopenic have very low aerobic capacity.69-71 Hypothetically, adding muscle mass to the sarcopenic individual will enhance adaptation to aerobic exercise69,72— another compelling reason for frail older adults with sarcopenia to participate in resistance training. Physical therapists regularly treat older adults who have a long history of inactivity and periodic bouts of disease- or illness-related bed rest. These patients are likely to have gained weight over the years and live in a society that poses little to no physical challenges. Thus, it is quite common for patients older than age 60 years to have V· o2max values in the 13 to 18 mL O2/kg/min range, which translates to inability to climb a flight of stairs without resting and inability to walk a quarter of a mile.73,114 Nearly all physical therapists have faced the challenge of the deconditioned older adult who is hospitalized, further imposing inactivity-related decline on a system that has nearly run out of cardiovascular capacity, and who reaches an unacceptably high HR just getting from bed to the bathroom. This scenario, reflecting enormous loss in cardiovascular reserve, is one major contributor to loss in homeostasis as well as loss of independence. Because of the fundamental changes in connective tissues, increased crosslinking of collagen, altered matrix composition, and loss of elastin, the entire vascular system, including the heart and peripheral vessels, is stiffer and less compliant.65,74 Most noticeable is the increase in blood pressure that occurs with age, the consequence of stiffer connective tissues within the vascular walls.62,65 Contractility of the left ventricle is compromised as well, which results in a reduction of cardiac output, one of the major components of V· o2max.70,75 In the author’s clinical experience, most (approximately 65%) of the clients older than age 70 years are medicated for hypertension. Rarely has the patient’s medication dosage been examined beyond a fundamental baseline blood pressure ascertained while the patient was sitting in the physician’s office. It is not uncommon to see patients overwhelm their hypertension medications during exercise. Consequently, from the standpoint of exercise safety, the physical therapist must watch for blood pressure increases that are unacceptably high. It is imperative that older adults perform warm-ups prior to aerobic exercise to accommodate for the slower arteriovenous oxygen exchange, stiffer vascular tissues, reduction in sympathetic nervous system output, and lower aerobic capacity associated with older age. Perhaps as a consequence of connective tissue changes, or other factors, the basement membrane in the capillary wall thickens with age.63,65,74 Thus, the exchange of oxygen and nutrients from the vasculature to working tissues occurs more slowly. Because tissue perfusion occurs more slowly, the “burn” in working muscles takes longer to subside during the initial phases of exercise, necessitating a warm-up longer than the usual requisite 3 minutes prior to more rigorous work. Thickening of the basement wall occurs in sedentary people but not in master athletes, which suggests that this aspect of “age-related” decline is actually a lifestyle modification.76 Indeed, an aerobic exercise training study of older (age 60 to 70 years), previously sedentary men and women revealed that basement membrane thickening was no longer present after 3 months of training at 70% or more of V· o2max.5 Whether membrane thickening occurs at older ages in men and women with a lifetime history of exercise is not known. Diseases of the peripheral vasculature such as diabetes and peripheral vascular disease (PVD) further increase basement membrane thickness, which can result in sufficient lack of oxygen perfusion to skin tissues for breakdown and nonhealing of ulcers. Lack of perfusion to skeletal muscle results in additional loss of fibers, and lack of perfusion to nerves leads to neuropathy.66 There is controversy in the literature as to whether the goal in the management of age-related increases in blood pressure is to achieve a blood pressure in the 120/80 range.77 Because of the increase in connective tissue stiffness within the vascular tree, there is currently a question if blood pressures of 140/80 should be considered as more “normal.” This should not be interpreted to suggest that increased blood pressure is not problematic. There is a substantial body of literature indicating that blood pressures that are too high can lead to stroke, and treating this condition increases life span.70 From a physical therapy perspective, the more important question is whether a patient is safe in our care. In a patient who is overmedicated, hypotension can result in dizziness and heightened risk for falling. Changes in medication are likely indicated. If patients have exercise pressures that are exceptionally high, medication modification is probably needed here as well. More clarity on what constitutes “normal” blood pressure for an 80-year-old versus that of a 60-year-old and a centenarian is needed. What are acceptable and safe blood pressures for sleeping, waking, exercising, and postprandial conditions for patients with heart disease is not known. Also unknown is whether age affects the effectiveness of treatments for hypertension. Peripheral to the discussion of age-related decline in the cardiovascular system is an issue of enormous importance to physical therapy: anesthesia. Men and women of all ages are affected by inhalation anesthesia, but the effects are most noticeable in older adults who have already lost a significant amount of cardiovascular
34 CHAPTER 3 The Physiology of Age-Related and Lifestyle-Related Decline reserve.Although inhala tes mito der adi aging.Nerve conduction tvationsad nrm anatomi any years us in is inhala- ad at wrist: nd tion anesthesia,muscular and cardiovascular endurance recorded the latency response at the hypothenar emi- s severely Physical therapists often see Response ere on average about 10 ms patien after tot. nt rep emen surgery, group (80 90 years day a change was ed with al eff ach s 30-year ade sadua s to ions of a slowing nervous phys apy has ome to end. r and co pha ical th of phy ide men ar use home exercise,proper gait pattern,and mobility e time to an induced s that therapy aimed fall was too slow recovery. In this instance,subjects giver aning rd into that was mal.The to the energy delivery system,bed wed to fall (an overhead suspension system ted an fsurgery,and inactivity indicate that perhaps from act study fo nd tha phys ltherapy y adul lts studi As a pro he imes to aspect of aging needs t0 wed which may ex num eart city are plain t mber o alls pe year in fear of a heart attack or stroke. The capable of reaching HR of maxi ing. where the person being tested must respond as mum. Institute and ot ca red lig prog ving the foot m nds ofb intry have the the i and for na ients with blatant cardiovas. n as the brake pedal is depres veen 150 and 250 ms,which wel ust c 500 b many Motc d pa do hea rate is within a trainir old)tested ranged f 0m350to1200m minutes ore risehas a modest effect on speed of reaction but the i n speed is not lik ve.N 30 ude to 27030im enge throughou the of a daily t 10 ds,which is still a long the 47 minutes of ex ercise bike followed by a rest followed by 10 conds expected of unger adults.Sev ral inve ninutes of alternating normal/bris mple ors hav onstrate a slight incre of ng aer heart in peg t in t f pe s centrally but sloug lin has de treatment. strated anatomically in peripheral nerv which will ce tainly slow conduc n velocity.It should be borne Nervous System chat mos ent spe There are fundamental cha within the central and t would also affect m Studies done to date have also not considered the poten- tial blunting effects of many drugs
34 CHAPTER 3 The Physiology of Age-Related and Lifestyle-Related Decline reserve. Although the mechanism is unknown, inhalation anesthesia obliterates mitochondria and, thus, the ability to deliver ATP during exercise is severely compromised.78 Thus, in our patients, after surgery with inhalation anesthesia, muscular and cardiovascular endurance is severely compromised.78 Physical therapists often see patients the day after total joint replacement surgery, often the day after fractured hip and, inevitably, these men and women become exhausted with minimal effort. It is no surprise that spontaneous improvement begins to manifest 2 months after the initial surgery or insult, long after physical therapy has come to an end. The initial phase of physical therapy following hip fracture is effective for teaching patients the essentials: transfers, walker use, home exercise, proper gait pattern, and mobility strategies. Evidence strongly suggests that therapy aimed at strengthening and endurance adaptations given to patients in the days immediately following surgery for hip fracture is ineffectual.79 The enormous devastation to the energy delivery system, coupled with bed rest, the trauma of surgery, and inactivity indicate that perhaps physical therapy intervention would be more effective 2 to 3 months after hospital discharge. As a profession, physical therapists need to reevaluate intervention effectiveness under these treatment conditions. One aspect of aging needs to be emphasized. Even though maximum heart rates and aerobic capacity are reduced, there is no reason that exercise in healthy older adults should be restricted to a low-intensity level for fear of a heart attack or stroke. The aging heart is fully capable of reaching HR zones of 70% to 80% of maximum.61,62,65,66,69,72 The Cooper Institute and other cardiac programs around the country have recorded tens of thousands of hours of strenuous exercise for older adults of all ages and for patients with blatant cardiovascular disease.80,81 To enhance cardiovascular endurance, exercise programs must challenge older adults. Walking a patient in the hallway 100 feet does not constitute an acceptable aerobic challenge for most people, unless heart rate is within a training zone of 60% to 80% of the HRmax estimated. For training to occur, elevated HRs have to be sustained for 20 minutes or more, which many older adults cannot achieve. Nonetheless, it is not unreasonable to accumulate 20 minutes of aerobic challenge throughout the course of a daily treatment. Five minutes of exercise bike followed by a rest followed by 5 minutes of alternating normal/brisk gait is an example of accumulating aerobic exercise.72 The heart, like any other muscle, must be challenged to grow stronger. Treating older adults like fragile objects is inadequate treatment. Nervous System There are fundamental changes within the central and peripheral nervous systems that have significant import for function. Slowing of the nervous system is an inherent aspect of aging. Nerve conduction studies of young and older adults confirm anatomic observations. Many years ago, Norris and colleagues stimulated the ulnar nerve 5 cm below the axilla, at the elbow, and at the wrist; and recorded the latency response at the hypothenar eminence. Response times were on average about 10 ms slower in men in the oldest age group (80 to 90 years) compared to 20- to 30-year-olds. Gradual change was apparent with each successive decade.82 Slowing of movement speed is one of the major clinical manifestations of a slowing nervous system. Examples abound but two will be given here. Alexander and colleagues identified the fact that even men and women in the young-old category (65 to 74 years) are already at heightened risk for falling as response time to an induced fall was too slow for recovery.83 In this instance, subjects were leaning forward into a harness that was preventing them from falling forward. Next, however, the harness was released and subjects were allowed to stumble and fall (an overhead suspension system prevented anyone from actually striking the ground). Their study found that most of the young-old healthy adults studied could not get their legs back underneath the body quickly enough and step appropriately to prevent a fall. Other studies from the same lab have indicated that response times to external perturbations to balance are slowed, which may explain the noticeable increase in number of falls per year in those older than age 60 years.84 In the author’s lab, reaction times have been assessed in hundreds of young and old healthy individuals. The task involved simulated driving, where the person being tested must respond as quickly as possible to a red light by moving the foot from the gas pedal to the brake pedal. The clock begins the instant the light changes from green to red and stops as soon as the brake pedal is depressed. Times for young adults ranged between 150 and 250 ms, which is well within the 500 ms cut-off time imposed by many Motor Vehicle departments for the same task. Reaction times for the approximately 150 healthy older adults (ranging 70 to 85 years old) tested ranged from 350 to 1200 ms. Exercise has a modest effect on speed of reaction but the increase in speed is not likely to attain sufficient magnitude to make an impact on function.85,86 Toe tap times, for example, increased after exercise from 27 to 30 in 10 seconds, which is still a long way from the 47 taps in 10 seconds expected of younger adults. Several investigators have demonstrated a slight exercise-induced increase in peg board times in that the number of pegs that could be moved in 30 seconds increased. Most of the slowing occurs centrally, but sloughing of myelin has been demonstrated anatomically in peripheral nerves, which will certainly slow conduction velocity. It should be borne in mind that most studies on changes in movement speed were performed on healthy individuals, not those with disease that would also affect movement speed further. Studies done to date have also not considered the potential blunting effects of many drugs
CHAPTER 3 The Physiology of Age-Related and Lifestyle-Related Dedine 35 B0X3-4 Maior elated Ch other facet of age elated decline is a fallout or loss of neurons.7ss Roughly half of the decline in muscle mass Anatomic/Phvsiological Clinical Consequences changes e only of myen nemtcion iss with far-reaching outcomes that affect the pathetic,parasympathetic,sensory,and motor system Before age-relatec decline begins,the yin-yang of the parasymp sympa to sensory input Loss of sensory neurons fght With age the balance of the Increased risk of falls likely relate ssues w ader cont flow to and from the periphery.The failure of the sym of mes ages from the dna.although many of the current pathetic nervous system to adequately respond to heat theories are likely to have some vera city few of the current n dea of many seniors as the perceive the aspec as mena with aging is altered somatic sensory input. ysical ther It is no evident that with advancing age area of systemic inflammation because of changes in the immu even t Is stem ory cyto and when an older in (CRP)and t rosis fac based on vague somatie complaints Abdominal pain could reflect a host of possible issues ranging from sim ple indig obstru Theincreaeine an underlying uld reflec ddiab irritation but could also reflect an abdominal aorta an eurysm, infection and cancer tory status may allow for more successful aging. ting thes aches to the mana ment c total-bod ar of fev .or in of crease or sharpening of svmptoms. cise Ofthe far superior to the Peripheral sensation adults,even hose indi th illustrate One cise bout result 125 abeeseeaidhcabcacoth8aieeatabn6hgg further reduce inflammation which should enable monofilament)in all persons tested(M.Brown,unpub. sive resent in thes ly physi ave m mation thar h the nhanced well-being of exercisers,who also have cessive heat or cold.Box 3-4 summarizes physiological wider window of homeostasis.These current findings changes of the nervous system and impact on function. nt role anagement o The Immune System ing functional decline through the use of exe cise An There are literally hundreds of theories on why we age example of the power of exercise is that many fewer men ranging from accumulated ind women who consistently exercise have Alzheimer's ase than ose who are sedentary
CHAPTER 3 The Physiology of Age-Related and Lifestyle-Related Decline 35 Although the aging of muscle is covered thoroughly in another chapter, it should be mentioned here that another facet of age-related decline is a fallout or loss of neurons.87,88 Roughly half of the decline in muscle mass is the consequence of neuronal, specifically, axonal loss.87 Indeed, muscle is not the only tissue that experiences loss of innervation; innervation declines in all tissues, with far-reaching outcomes that affect the sympathetic, parasympathetic, sensory, and motor systems. Before age-related decline begins, the yin–yang of the parasympathetic and sympathetic nervous systems is delicately balanced and poised to participate in flight or fight. With age, the balance of the parasympathetic and sympathetic nervous system output is altered (although poorly defined) and likely related to the slowing of gastric motility, possible issues with bladder control, hypertension and hypotension, and deficits in control of blood flow to and from the periphery.89 The failure of the sympathetic nervous system to adequately respond to heat and cold is responsible for the deaths of many seniors each summer and winter as they failed to perceive the need to cool down or warm up. One of the most complex and poorly understood phenomena with aging is altered somatic sensory input.89,90 It is common for vague symptoms of pain in one area of the body to represent a totally unrelated event. It is a tremendous challenge for physical therapists to discern if and when something is wrong with an older patient based on vague somatic complaints. Abdominal pain could reflect a host of possible issues ranging from simple indigestion to pancreatitis, cancer, intestinal obstruction, peritonitis, impending heart attack, or inguinal hernia. Back pain could reflect a simple muscle or joint irritation but could also reflect an abdominal aorta aneurysm, appendicitis, bladder infection, and cancer. Carefully noting these complaints is important, particularly if complaints are coupled with sudden change in function, sensorium, the emergence of fever, or an increase or sharpening of symptoms. Peripheral sensation gradually diminishes in older adults, even those individuals without vascular diseases or neuropathy secondary to diabetes. To illustrate, Semmes-Weinstein testing on 125 older adults without diabetes revealed the absence of normal sensation (6.13-g monofilament) in all persons tested (M. Brown, unpublished data). Protective sensation was still present in these individuals (5.07-g monofilament), but fine discrimination was lacking. The blunting of peripheral sensation undoubtedly contributes to the inability to perceive excessive heat or cold. Box 3-4 summarizes physiological changes of the nervous system and impact on function. The Immune System There are literally hundreds of theories on why we age, ranging from accumulated wear and tear to programmed apoptosis to the accumulation in errors during translation of messages from the DNA. Although many of the current theories are likely to have some veracity, few of the current theories have import for physical therapy. Recently, however, one aspect of age-related decline has emerged as a major contributor to the loss of muscle and organ reserve that has considerable import for physical therapy. It is now evident that with advancing age, there is an increase in systemic inflammation because of changes in the immune system. Major increases in known proinflammatory cytokines such as interleukin 1 and 10 (IL-1, IL-10), C-reactive protein (CRP), and tumor necrosis factor–a (TNF-a) occur with advancing age, which is significantly associated with muscle wasting and loss of physical function.6,7,14,46,72,91,92 The increase in systemic inflammation is also an underlying factor in the development of age-related diseases such as Alzheimer’s disease, atherosclerosis, cancer, and diabetes.91,93 Thus, it is hypothesized that controlling inflammatory status may allow for more successful aging.8,94,95 Four approaches to the management of total-body inflammation have been considered: anti-inflammatory drugs, use of antioxidants, caloric restriction, and exercise.6,94-96 Of the three, exercise is far superior to the minimal impact noted from anti-inflammatory drugs and antioxidants.21,27,48,53 One exercise bout results in a significant reduction in markers of inflammation such as IL-1 and TNF-a. 48,50,92,93 Cumulative exercise sessions further reduce inflammation, which should enable chronic exercisers to resist fatal infections and aggressive pathogens.97 Men and women who are habitually physically active have less systemic inflammation than those who are sedentary, which may be the major reason for the enhanced well-being of exercisers, who also have a wider window of homeostasis. These current findings suggest that physical therapy can play an important role in the management of systemic inflammation, enhancing systemic “reserve,” reducing risk for disease, and delaying functional decline through the use of exercise. An example of the power of exercise is that many fewer men and women who consistently exercise have Alzheimer’s disease than those who are sedentary.91,93 BOX 3-4 Major Age-related Changes in the Nervous System and Associated Clinical Consequences Anatomic/Physiological changes Clinical Consequences Sloughing/loss of myelin Slowed nerve conduction Axonal loss Fewer muscle fibers Loss of fine sensation Autonomic nervous system dysfunction Slower systemic function (e.g., C-V, GI) with altered sensory input Loss of sensory neurons Reduced ability to discern hot/cold, pain Slowed response time (speed of reaction) Increased risk of falls
36 CHAPTER3 The Physiology of Age-Related and Lifestyle-Related Decin mass fr specific musc mmediately by about 15 e g fic for When estroger metabolically active and is an inflammatory organ.Not hear complaints of weakness from women who funct rats provide an exp s reserve anc stas The Finding important. any From a rehabilitation perspective,several mpor The Hormonal Axis tant fin ings have bee reported on estrogen-d r is a loss of ho om rode bed r and strength fails to occu or occurs more slowly in “senile ot uncommon for pricury in sk estrogen- ehcit rats. These findings may provide an explanation women do not muscle wen as ry,severe traun s.Rodent studies also 8th decade are hypogonadal. Recently,the loss of indicate that estrogen-deficient muscle is more suscep- sex hormones has been the rec and.o nine tributor tible to injury,whic may be anoth m2 strength women testosterone replacement gain a significant amount of Replacement of one hormone may not be sufficient to overcome a specific defi icit as hormones tend to worl change un re n one another - ase m the growt th fa 、10 meta-analysis concluded that er.if IGF-I levels are already low.then per steroid that is associated with an iner ease in strength and the utility of testosterone is limited.One scientist has lear and co recomm de scle replacement,particularly 50057 men as t mass at a n groups:control. ho the ies multiple hormones should be administered simulta (HRT),exercise,or HRT plus exercise.Subjects wer in the rescarc study for ised two to three deficiencies in othe lmes a we wing the ancy an umn height and runnine d w ed Th in the HRT and exercise plus HRT groups(not the exer- the vears abead cise only group) ihcant increa ses in running and er EXERCISE FOR REVERSING DECLINE ed A udy of AND PREVENTING DISEASE It is becoming evident that a lifestyle that includes rou has furthel estrogen effe tremely women t wer 5 and yea line an arthritis ascular dise ously,knee extension strength was not greater.Othe syndrome,pain,and Alzheimer's disease,to name a few. ength e that physical findings in musele de. ntial to n mote health o than care professional,and it should be the profession's mis- sion to do so
36 CHAPTER 3 The Physiology of Age-Related and Lifestyle-Related Decline One of the probable contributors to the rise in inflammation is the shift in fat mass from the periphery to the abdomen coupled with the general increase in total intraabdominal fat with advancing years.27,51 Abdominal fat is metabolically active and is an inflammatory organ. Not only do inflammatory cytokines result in muscle wasting, they diminish the function of other organ systems as well, which reduces reserve and shrinks the window of homeostasis. The increase in inflammatory cytokines is also associated with metabolic syndrome.98 The Hormonal Axis One of the realities of aging is a loss of hormones, a loss in responsiveness of hormone target tissues, or both.27,31,99 It is not uncommon for older adults to develop “senile” diabetes because insulin sensitivity, particularly in skeletal muscle, is reduced.99 Women after menopause have little estrogen, and men lose testosterone throughout the course of a lifetime, such that the majority of men in the 8th decade are hypogonadal.99,100 Recently, the loss of sex hormones has been determined to be a contributor to the reduction in muscle mass and, in particular, muscle strength.100,101 Indeed, older hypogonadal men given testosterone replacement gain a significant amount of lean mass although data suggest that the increase in mass is not accompanied by much strength change unless resistance exercise and testosterone are given together.99 Loss of estrogen has only recently received interest. A meta-analysis concluded that estrogen is an anabolic steroid that is associated with an increase in strength and lean mass in postmenopausal women.102 Taafe and coworkers conducted a double-blind study of 80 women (50 to 57 years) who were randomly assigned to one of four groups: control, hormone replacement therapy (HRT), exercise, or HRT plus exercise. Subjects were in the research study for 1 year and exercised two to three times a week. Prior to and following the year enrollment, lean mass of quadriceps and hamstrings, strength, vertical jump height, and running speed were assessed. Those in the HRT and exercise plus HRT groups (not the exercise only group) had significant increases in running speed, muscle mass in both compartments and vertical jump height compared to controls. No strength measures were reported. A recent study of postmenopausal twins, one of whom was on HRT whereas the other was not, has further substantiated estrogen effectiveness.101 The women taking HRT were between 5 and 15 years postmenopause. Vertical jump height, fast gait, and grip strength were higher in the twin taking hormones. Curiously, knee extension strength was not greater. Other studies of older postmenopausal women suggest the same important outcome: more muscle mass and strength with HRT.103 One of the most interesting findings in muscle deprived of estrogen was reported in several studies of rats. When ovaries were removed, simulating menopause, specific muscle force (force/unit of muscle mass) almost immediately declined by about 15%.104 When estrogen was returned to the system, specific force normalized back to baseline values.105 It is not uncommon to hear complaints of weakness from women who have undergone ovariohysterectomy. Perhaps these findings from rats provide an explanation for these complaints. Findings also suggest that strength training for postmenopausal women at any age is particularly important. From a rehabilitation perspective, several important findings have been reported on estrogen-deficient muscle from rodents. When muscle atrophy is induced in rats (simulated bed rest), recovery of muscle mass and strength fails to occur or occurs more slowly in estrogen-deficit rats.106-108 These findings may provide an explanation for why women do not progress as well as men with spinal injury, severe trauma, or head injury, all conditions that cause estrogen values to plummet to undetectable ranges. Rodent studies also indicate that estrogen-deficient muscle is more susceptible to injury, which may be another factor influencing recovery of muscle mass and strength in women who are estrogen-deficient.109-112 Replacement of one hormone may not be sufficient to overcome a specific deficit as hormones tend to work in concert with one another. For example, testosterone has been shown to increase insulin-like growth factor-I (IGF-I), which stimulates protein synthesis in muscle.100 However, if IGF-I levels are already low, then perhaps the utility of testosterone is limited. One scientist has recommended hormone replacement, particularly for men as they lose muscle mass at a more rapid rate than women. His conclusion was that perhaps in future studies multiple hormones should be administered simultaneously as low values in one hormone are likely to reflect deficiencies in other hormones.113 Hormone supplementation is in its infancy and should bring considerable change. An enhanced understanding of how hormones can influence health and well-being is to be expected in the years ahead. EXERCISE FOR REVERSING DECLINE AND PREVENTING DISEASE It is becoming evident that a lifestyle that includes routine exercise can be extremely influential in preventing physical decline and disease. Those who exercise routinely (at any age) have less cardiovascular disease, osteoarthritis, diabetes, vascular disease, metabolic syndrome, pain, and Alzheimer’s disease, to name a few. Studies of Masters athletes and habitual exercisers indicate that physical activity promotes optimal well-being and enhanced self-efficacy.114,115 Physical therapists have more potential to promote healthy aging than any health care professional, and it should be the profession’s mission to do so