Division of Endocrinology, Metabolism, and Molecular Medicine, Charles R. Drew University of Medicine and Science, Los Angeles, California 90049
Address all correspondence and requests for reprints to: Shalender Bhasin, M.D., Division of Endocrinology, Metabolism and Molecular Medicine, Charles R. Drew University of Medicine and Science, University of California at Los Angeles School of Medicine, 1621 East 120th Street, Los Angeles, California 90059. E-mail: sbhasin{at}ucla.edu
AGING in humans is associated with a progressive decrease in skeletal muscle mass and strength (sarcopenia) that contributes to frailty and falls. The age-associated changes in body composition result from lower levels of anabolic hormones, neuromuscular alterations, and a general decline in muscle protein turnover (1, 2, 3). The frailty of old age has emerged as an important public health problem because it impairs mobility and quality of life and increases the risk of falls and the use of health care resources (4, 5, 6). Therefore, recent years have witnessed a growing interest in the use of anabolic interventions for augmenting muscle mass and function in older men.
Pathophysiology of Sarcopenia
Pathophysiology and epidemiology of sarcopenia
The term sarcopenia, originally coined by Rosenberg (4) and
recently reviewed by the National Institutes of Aging (5), refers to
the involuntary loss of skeletal muscle mass and strength. This is in
contrast to wasting, the involuntary loss of weight driven largely by
inadequate nutrition, and cachexia, the involuntary loss of fat-free
mass (FFM), especially body cell mass, generally resulting from a state
of hypermetabolism and hypercatabolism (6). The etiology of sarcopenia
is currently unknown. Holloszy (5) identified several possible
mechanisms leading to sarcopenia, including loss of motor neurons
in the spinal column, impairment of endogenous growth hormone, androgen
and estrogen production, inadequate protein intake, dysregulation of
catabolic cytokines, and reduced physical activity.
Mortality in the elderly is primarily associated with atherosclerosis, cancer, and dementia. In an increasing number of the elderly men and women, however, loss of muscle mass and strength is an important determinant of the individuals ability to live an independent life (7). There is no consensus on whether sarcopenia should be viewed as a disease or process of normative aging (4). It has been argued that, because loss of muscle mass occurs even during the course of successful aging, sarcopenia should be considered a disease only when it induces disability (4). There is also no consensus on what threshold of muscle loss should be used to define sarcopenia.
The magnitude of the public health problem posed by sarcopenia is not known (8). Baumgartner et al. (9) examined the prevalence of sarcopenia in Hispanic and non-Hispanic white elderly men and women in New Mexico. Sarcopenia was defined as the relative muscle mass that was two SDs below the sex-specific means of the Rosetta Study reference data (10) for young adults, aged 1840 yr. The study (9) demonstrated that the prevalence of sarcopenia increased from 13% to 24% in persons under 70 years of age. Nearly half of all persons over 80 years of age met this definition of sarcopenia. The study also demonstrated that sarcopenia was associated with a 3- to 4-fold increased likelihood of disability in elderly people, independently of age, sex, obesity, ethnicity, socioeconomic status, chronic morbidity, and health behaviors (9).
Another cross-sectional survey performed by Melton (11) in Olmsted County in Minnesota used slightly different thresholds for defining sarcopenia and reported lower prevalence rates. Based on an age-stratified, random sample of the population of Rochester, Minnesota, this survey verified the findings of Baumgartner et al. (9) that lean body mass decreases progressively after the second decade of life in both men and women. Age-related losses in fat-free mass, appendicular muscle mass, and total muscle mass are all linear in both men and women, and there was no significant difference in the slope of the regression line before 50 and after 50 years of age. The prevalence of sarcopenia in individuals over 20 years of age was 23% and in those over 65 years of age, approximately 10% (11). Taken together, these two epidemiological studies provide evidence that sarcopenia is an important public health problem.
Aging-associated changes in body composition
In the two-compartment model of body composition, body weight is the combination of fat mass and fat-free mass. Fat-free mass, in turn, is the combination of body cell mass, extracellular fluid, and the extracellular solids such as collagen and bone mineral. Body cell mass can be further divided into the fat-free portion of cells within muscle, viscera, and the immune system. Muscle cell mass is an important determinant of muscle strength, whereas the sum of visceral and muscle body cell mass predicts energy requirements (6). Thus, changes in body composition with aging, especially in the FFM component, have important implications for functional status and survival (6, 13).
Weight gain in adults is associated with an increase in absolute and percent fat mass (14). In women, body weight increases between the ages of 40 and 50 yr and remains stable thereafter; percent body fat is also stable until 40 yr of age and increases from 28% to 35% between 40 and 50 yr of age (15). In another cross-sectional study (16) of men and women 1885 yr of age who used total body potassium, percent fat increased from 18% to 36% and 33% to 44% in men and women, respectively. In addition to an overall increase in adiposity, aging is associated with a more central distribution of fat (14). The composition of lean tissues also changes with advancing age. Men experience a more rapid muscle loss between the ages of 41 and 60 yr, whereas women experience the rapid loss after the age of 60 (17). Total body nitrogen, calcium, water, and bone mineral content also decline with age (18, 19, 20, 21). More recent epidemiological surveys suggest that age-associated decrease in skeletal muscle mass starts after the second decade of life in both men and women and is slowly progressive thereafter.
The principal component of the decrease in fat-free mass is the loss of muscle mass; there is little change in nonmuscle lean mass (18, 19). Between 20 and 80 yr of age, the cumulative decline in skeletal muscle mass amounts to 3540% (22, 23). The depletion of muscle mass does not result in weight loss because of the corresponding accumulation of body fat (24).
Muscle atrophy results from a gradual and selective loss of muscle fibers. The number of fibers in the vastus lateralis muscle from cadavers of older men is 23% lower than in young men (26). There is a preferential atrophy of fast-twitch, type II fibers (24), in part because of their reduced reinnervation capacity than type I fibers (26). There is an increase in intramuscular fat and connective tissue (27). These changes reduce the contractile tissue volume available for locomotive and metabolic functions and the increased amount of connective tissue presumably acts as a friction brake to slow contractile velocity (24, 28).
Most studies of muscle mass and body composition have relied on cross-sectional data. Many of these studies have not taken into account individual variation due to the level of physical activity, nutritional status, and disease. There is also a paucity of data on ethnic differences in body composition.
Changes in muscle function
Sarcopenia has been identified as a contributor to disability in old age (29, 30). Walking, stair climbing, rising from a chair, and load carrying represent functional activities that deteriorate with sarcopenia. Loss of muscle mass, particularly the preferential loss of type II fibers (24), results in diminished strength and power-generating capacity (31). There is a significant correlation between strength and leg power and maximal walking speed and stair-climbing height (31, 32, 33, 34). Rantanen and Avela (34) have described critical ranges of leg power for different walking speeds, suggesting that below the critical range the probability of walking at a particular speed is low.
Falls are a serious consequence of the loss of muscle strength and power. Leg weakness and decreased peak torque and power are associated with impaired gait characteristics, such as small steps and slow speeds (35) and a history of falling (36, 37). Because strength is fundamental to the neuromuscular function that supports mobility (37), loss of strength below a critical threshold may be associated with an increased risk of falls. Therefore, interventions that increase muscle mass, strength, and power in the lower extremity may reduce the risk of falling.
The maximal oxygen uptake rate (VO2max) defines the capacity for endurance exercise (22). Both decreased muscle mass (23) and decreased oxidative capacity of skeletal muscle (38) with aging contribute to the 1% annual decline in maximal aerobic capacity. Resistance training can increase VO2max in the elderly (39); this suggests that increasing muscle mass can increase maximal aerobic power. Sarcopenia contributes to the decline of aerobic capacity, thus limiting the extent to which older individuals may participate in a variety of activities and retain their independence. Therefore, interventions that augment muscle mass can help older men maintain or regain their ability to perform daily functional activities and live independently.
Changes in muscle protein dynamics
Approximately 20% of muscle weight is protein; therefore, changes in muscle mass will likely be associated with alterations in muscle protein turnover (which includes muscle protein synthesis and break down) (14, 24). Whole body protein synthesis declines from birth to old age (40). However, when protein turnover rates are normalized to FFM, there is no difference between young and old subjects (41, 42). Because older people lose FFM but not weight, it is possible that the difference observed in whole body protein synthesis in the elderly is due to their increased fat mass (14). Also, the muscle contributes <30% to whole body protein turnover; therefore, small changes in muscle protein synthesis or breakdown are difficult to detect with measurements of whole body protein turnover. Indeed, the fractional synthesis rates of mixed or myofibrillar protein are lower from muscle biopsy samples in old people as compared with young people (42, 43, 44). Standardized exercise programs, testosterone, and amino acids can stimulate the synthetic rates of total muscle protein (44), as well as myofibrillar proteins (45). In contrast, high-protein meals do not enhance the stimulation of myofibrillar synthesis induced by resistance exercise (45). Because amino acids alone can stimulate muscle protein anabolism in young and older subjects (46), it is unlikely that alterations of muscle protein metabolism in the elderly are due to a defect in amino acid transport.
There are alterations in the synthesis rates of individual muscle proteins in older individuals. Compared with younger subjects, the middle-aged and older men and women have significantly lower synthetic rates of myosin heavy chain, an important contractile protein (47). The fractional myofibrillar protein synthesis rate (the rate of synthesis per gram of myofibrillar protein already present) is 28% slower in older subjects (42). The reduced myofibrillar protein synthesis in the elderly is not due to a reduction in the availability of mRNAs encoding actin and myosin (48) and may be the result of posttranslational events.
Protein turnover is important for maintaining the mass of structural and contractile proteins and enzyme function (24). There is a 40% decrease in mitochondrial protein synthesis rates in middle-aged subjects, but no further decrease in older subjects (49). The changes in mitochondrial function may contribute to alterations in muscular endurance and fatigability and contractility (24).
Although it is now possible to measure synthesis and breakdown rates of specific muscle proteins and to study their regulation (14, 47, 49, 50), these methods are invasive and are not clinically applicable to older individuals with sarcopenia. We have little information about the genetic regulation of skeletal muscle protein turnover in humans.
Changes in hormones
Aging is associated with changes in several trophic factors (51), including the male sex hormones and the growth hormone axes (52).
Testosterone. There is an age-associated decrease in serum total and free testosterone levels in healthy men (53). A meta-analysis of 44 studies demonstrated an unequivocal decrease in morning testosterone levels in older men (54). Lower testosterone levels are the result of changes at multiple levels of the hypothalamic-pituitary-gonadal axis (55). Testicular response to gonadotropins is diminished in older men, gonadotrope responsiveness to androgen suppression is attenuated, and the pulsatility of the hypothalamic GnRH pulse generation is altered. Coexisting diseases, malnutrition, and concomitant medications can also affect serum testosterone levels (55).
Although, as a group, serum testosterone levels are statistically lower in older men than those seen in younger men, many older men have normal or low-normal testosterone levels, leading to speculation that older men might be relatively insensitive to the end organ effects of testosterone. The androgen receptor number and affinity are decreased in many organs of the aging rat (56, 57). However, in the human, older men have increased rather than decreased sensitivity to androgen feedback effects on pituitary LH and FSH secretion (58). This issue of androgen insensitivity of muscle and bone to testosterone effects in older men has not been studied.
There is no consensus on the serum testosterone levels that can be used to define androgen deficiency in older men. We do not have a clinically useful biological marker of androgen action. Total testosterone level below 200 ng/dL or bioavailable testosterone levels below 60 ng/dL warrants replacement, especially if associated with symptoms suggestive of androgen deficiency.
GH. There is abundant evidence that GH secretion declines with age. Because GH is an anabolic agent, it has been suggested that some of the changes in body composition with age may be related to decreased GH production. The 24-h integrated secretion of GH and acute GH secretory responses to exercise and GHRH stimulation are decreased in older men and women, as compared with healthy young men (59). Circulating insulin-like growth factor (IGF-1) levels are lower in older men than young men; the serum IGF-1 levels in older residents of nursing homes are in the lowest tertiles for healthy young men (59). Serum IGF-1 levels correlate positively with maximal aerobic capacity and leisure time physical activity and negatively with adiposity in older men. After reaching a peak in mid-adulthood, GH-binding protein levels decrease after the 6th decade of life (60).
Dehydroepiandrosterone (DHEA). DHEA and its sulfated form, DHEAS, are produced in large quantities by the adrenal glands in humans, nonhuman primates, and some nonprimate species (62, 63). DHEA metabolism is substantially different in rodents than it is in humans. The circulating concentrations of DHEA are thousand-fold lower in rodents than humans (62, 63). Also, in rodents, the gonads rather than the adrenal glands are the source of circulating DHEA.
Circulating concentrations of DHEA and DHEAS in humans increase progressively starting at about 57 yr. After reaching a peak in the 20s, serum DHEA levels decline, and this rate of decline accelerates after the 8th decade of life. This has led to the hypothesis that the age-related changes in body composition, insulin sensitivity, and diseases of old age may be related to DHEA deficiency (64). The decline in DHEA and DHEAS parallels the decline of the GH/IGF-1 system (64).
DHEA serves as a multifunctional steroid precursor that is converted in the body to testosterone and estrogen. No specific binding site has been described for DHEA in any human organ, and we do not know whether DHEA has physiological effects other than those mediated through its conversion to testosterone and estrogens (64, 65, 66).
Anabolic Interventions
Testosterone
There is agreement that replacement doses of testosterone increase FFM, muscle size, and maximal voluntary strength in young, healthy, androgen-deficient men (67, 68, 69, 70). Serum testosterone levels correlate inversely with fat mass, particularly visceral fat mass; however, not all studies report a reduction in fat mass after testosterone replacement of hypogonadal men (67, 68, 69, 70).
The effects of testosterone supplementation on muscle strength and
physical function in older men are unknown. Several short-term studies
(52, 69, 71, 72, 73, 74, 75, 76) have examined the anabolic effects of testosterone
replacement on body composition in older men with low testosterone
levels (Table 1). Tenover (53)
administered testosterone enanthate, 100 mg per week, or placebo, for
12 weeks to older men with testosterone levels of <400
ng/dL-1. In this double-blind, placebo-controlled,
crossover study, FFM increased by 1.8 kg after testosterone
replacement. In another study (71), administration of 200 mg
testosterone enanthate given every 2 weeks to older men with
bioavailable testosterone levels of <70 ng/dL-1 was
associated with a modest increase in hand grip strength, but body
composition did not change. Haddad et al. (73) reported a
significant increase in FFM and strength in hypogonadal men treated
with a scrotal testosterone patch for 6 months. Urban et al.
(74) reported increased fractional muscle protein synthesis and muscle
IGF-1 messenger RNA expression in the testosterone-treated older
men.
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In another long-term study, Tenover (75) demonstrated significant improvements in FFM, hand grip strength, and bone density in older men with serum testosterone <350 mg/dL-1 who were treated with a replacement dose of testosterone enanthate for 3 years.
Snyder et al. (76) examined the effects of testosterone replacement by means of a scrotal testosterone patch (6 mg per day) for 36 months in men over 65 years of age. The investigators randomized 108 older men over the age of 65 to receive either a placebo patch or testosterone scrotal patch designed to nominally deliver 6 mg testosterone daily. Ninety-six of 108 enrolled men completed the protocol. Mean testosterone concentrations increased from 367 ng/dL to 625 ng/dl in men treated with the testosterone patch, but did not change in placebo-treated men.
Testosterone treatment was associated with a significant decrease in fat mass (mean reduction in fat mass, 3 kg) and an increase in lean body mass (mean increase in lean body mass, 1.9 kg) as compared with placebo-treated men. Overall, the change in bone mineral density was not significantly different between the placebo- and testosterone-treated men (76). Further analysis revealed that bone density increased by about 6% in men with baseline testosterone levels of 200 ng/dL, but did not change in those with baseline testosterone levels of 400 ng/dL or greater. This treatment did not significantly increase the strength of knee extension and flexion. Testosterone treatment was well tolerated, and the frequency of prostate events was not significantly different between the placebo and testosterone groups. There were significant increments in hemoglobin levels in testosterone-treated men (76).
Taken together, the landmark studies of Tenover (75) and Snyder et al. (76) demonstrate that physiological testosterone replacement in older men with low testosterone levels produces modest increases in lean body mass, bone mineral density, and grip strength. We do not know whether physiological testosterone replacement can induce clinically meaningful changes in muscle function, reduce falls and fractures, or improve quality of life in older men. Also, the effects of testosterone supplementation in frail elderly, particularly the oldest old, the population that is the most at risk for falls, fractures, and debility, have not been examined. The long-term safety of testosterone supplementation of older men, particularly with respect to the risk of cardiovascular disease and prostate cancer remains to be established. Most studies of the androgen effects have used relatively low doses of testosterone. It is conceivable that a higher testosterone dose may yield larger effects. The data on the dose-response relationship between serum testosterone levels and muscle strength are needed to optimize the clinical efficacy and safety of testosterone regimens for use in older men.
GH
Several short-term clinical trials are in agreement that human GH
supplementation in older men increases apparent lean body mass and
decreases fat mass (Table 2) (77, 78, 79, 80, 81).
Because most methods of body composition are susceptible to changes in
body water, it is possible that apparent increase in lean body mass may
partly reflect water accumulation. There are gender differences in GH
response to provocative stimuli and in physiological responses to GH
replacement therapy (82, 83). In general, premenopausal women
experience greater GH secretion in response to pharmacological stimuli
than men (82). In contrast, GH-deficient men are more responsive to GH
replacement than women (83). During treatment, GH-deficient men have a
greater increment in IGF-1 levels, a greater decrease in fat mass and
plasma lipids, and a greater change in markers of bone formation and
resorption (83) than GH-deficient women.
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The response to GH therapy may be modulated by sex steroids. For instance, Ivey et al. (87) evaluated the effects of GH administration alone and in combination with testosterone and estrogen replacement in older men and women, 6588 yr of age. In this study, GH administration alone increased muscle mass and muscle cross-sectional area; combined administration of GH and 100 mg testosterone enanthate every 2 weeks was associated with a greater increase in muscle cross-sectional area and a greater reduction in percent fat than either intervention alone. These data suggest that the effects of rhGH on body composition may be augmented by concomitant administration of low doses of testosterone.
Nutritional supplements
In recent years, several new steroids such as androstenedione, androstanediol, and DHEA and nutritional supplements have become widely available in health food stores.
DHEA. Low DHEAS levels have been correlated with an increased risk of breast cancer in women, higher cardiovascular morbidity in men, and the decline of immunocompetence during aging (64, 65, 66). DHEA is widely available in health food stores and over the Internet as a "nutritional supplement" and is advertised as a panacea for many aging-associated ailments including diabetes, obesity, heart disease, Alzheimers disease, and muscle weakness. Most of these claims are based on studies performed in rodents in whom the basal DHEA levels are thousand-fold lower than the levels in humans. The doses of DHEA used in the rodent studies have been relatively high and should be viewed as pharmacological. Administration of pharmacological doses of DHEA to rodents is associated with improvements in immune function and memory, reduction of fat mass, and inhibition of the development of diabetes, atherosclerosis, and cancer. In mouse models of obesity, DHEA administration reduces the rate of weight gain. However, these rodent data have yet to be confirmed in human studies.
DHEA administration to postmenopausal women is associated with increments in serum testosterone, androstenedione, estrone, estradiol, and IGF-1 levels (88). However, the human studies of DHEA either show no change or a worsening of insulin sensitivity and plasma high-density lipoprotein levels (89). Although some studies (62) report a significant reduction in fat mass with 1600 mg DHEA (50 times the daily production rates of DHEA in young men) given daily for 4 weeks, others have found no change in body composition.
Yen et al. (90) reported that administration of DHEA in older subjects increased DHEA blood levels and increased biologically active IGF-1; however, another study by the same group reported no change in lean body mass. Morales et al. (88) demonstrated that 100 mg daily dose of DHEA restored the circulating DHEA, DHEAS and IGF-1 levels in older men and women to those seen in young men and women, and significantly increased lumbar and knee muscle strength in men (88). However, others have found no change in body composition after administration of 100 mg DHEA daily for 6 months (89). Therefore, it remains unclear whether physiological DHEA replacement has beneficial biological effects in humans and claims of its potency remain unsubstantiated.
Androstenedione. Androstenedione is a steroid hormone produced endogenously by the adrenal glands and gonads of both sexes and is an intermediate in the androgen and estrogen biosynthetic pathway. Androstenedione is synthesized from DHEA and is then converted to testosterone by the enzyme 17ß-hydroxysteroid dehydrogenase or to estrone by the aromatase enzyme. Androstenedione is available over-the-counter and is marketed primarily to athletes and people interested in bodybuilding. The number of people taking androstenedione regularly is not known. The prevalence of lifetime use of illegal androgenic steroids in the United States has been estimated to be 0.9% among men and 0.1% among women (92, 93, 94, 95). Among 12th grade males, the prevalence of lifetime use of illegal androgenic/anabolic steroids was 3.2% in 1996 (94, 95). It is likely that androstenedione use is even more common. Because supraphysiological levels of testosterone have been shown to increase muscle size and strength (96), many people claim that orally administered androstenedione will have similar anabolic effects.
An uncontrolled study reported that a single 100 mg dose androstenedione increased serum testosterone levels significantly in two women (97). The magnitude of the increase (about 100 ng/dL), however, was small. Two small, unpublished studies (98, 99) have examined the effects of oral androstenedione administration on testosterone levels in men. In one study (98), 100 mg androstenedione was given to six men for 5 days. Plasma androstenedione and estradiol levels increased, but plasma testosterone levels did not change. Moreover, protein synthesis did not increase (98). In another study (99), 100 and 200 mg doses androstenedione were administered to six men for 7 days. Serum androstenedione levels increased slightly, but serum testosterone, estrone, and estradiol levels did not change (99). A third study (100) examined the effects of treating men with 100 mg androstenedione thrice daily for 10 weeks in an intermittent regimen in which 2-week intervals of drug administration were followed by 2-week periods in which the drug was not administered. The total exposure, therefore, was <6 weeks, which may have been insufficient to produce significant changes in body composition. Only 10 men received androstenedione; the sample size may have been too small to detect small, but significant, treatment effects. No significant changes in serum testosterone levels or muscle strength were found (100). The treatment groups in this study included resistance exercise alone and resistance exercise plus androstenedione; the effects of androstenedione alone were not examined. Therefore, we do not know, at present, whether androstenedione has any beneficial effects.
Creatine. Creatine, a natural nutrient found in animal source foods, is purported to have ergogenic effects on exercise performance. It has been argued that phosphorylation of creatine into phosphocreatine (PCr) and the subsequent donation of the phosphate group to adenosine diphosphate to form adenosine triphosphate serves as an important source of chemical energy for muscle contraction (91). The hypothesis is that increased stores of PCr within the muscle can help to rapidly replenish PCr and adenosine triphosphate during exercise. However, data on the effects of creatine on body composition and muscle function are inconclusive because of problems of study design. Some studies report enhancement of body weight and lean body mass with creatine supplementation, others have found no significant change in body composition or muscle performance. In an 8-week, placebo-controlled study conducted by Bermon et al. (101), subjects were randomly assigned into one of four groups: creatine but no exercise training; creatine plus training; placebo but no exercise training; and placebo plus training. Oral creatine supplementation, with or without a program of resistance exercise training, failed to demonstrate any increase in strength or endurance. The study also failed to show any significant changes in body composition, as measured by lower limb muscular volume. The beneficial effects of creatine on body composition and muscle function remain to be demonstrated.
Chromium picolinate. The claims that chromium picolinate has ergogenic properties and augments lean body mass, skeletal muscle size, and strength (102, 103, 104) lack validity. A well-controlled study by Campbell et al. (104) failed to demonstrate any beneficial effects on body composition and muscle function. In this randomized, placebo-controlled study, 18 men were assigned to receive either chromium picolinate or placebo in addition to participating in resistance training for 12 weeks. The authors report that chromium picolinate supplementation did not enhance muscle size, strength, or lean body mass accretion in older men during a resistance training program. Data from other studies, on which claims of efficacy are based, are inconclusive.
Strength training
Skeletal muscle mass is very responsive to changes in physical activity. Therefore, the decrease in activity with advancing age may contribute to the multifactorial pathophysiology of sarcopenia (105). The loss of muscle mass may lead to further reduction in the level of physical activity, thus accelerating the downward spiral of skeletal muscle dysfunction (5).
Exercise, specifically strength training, is the only known
nonpharmacological intervention that can reverse some of the functional
changes seen with aging (105, 106). Strength or resistance training
involves a progressive increase in resistance, over time, against which
a muscle generates force (106). Muscle strength increases in response
to training using resistance that equals or exceeds 60% of the one
repetition maximum (1RM; the maximum of amount of weight that can be
lifted with one contraction) (106). The increase in muscle size with
strength training is largely the result of increased accretion of
contractile protein (106). The mechanisms by which strength training
increases muscle mass are not understood. The effects of strength
training on effort-dependent muscle strength and body composition in
older men have been examined in several short-term studies (Table 3).
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Fiatarone et al. (115, 116) have demonstrated the beneficial effects of progressive resistance training in frail, institutionalized elderly individuals. These investigators have reported dramatic gains in muscle strength, muscle cross-sectional area, and tandem walking distance following an 8-week program of resistance exercise training in frail, institutionalized elderly men and women (mean age, 90 years). The maximum voluntary strength of the knee extensors increased 174%, mid-thigh cross-sectional area increased 9%, and tandem gait speed increased 48%. These data demonstrate that even in the oldest old, the capacity of the aging musculoskeletal system to adapt to increased levels of physical activity is preserved. More importantly, strength training can be safely administered to the frail elderly and may restore some of the age-related loss in function (117).
Conclusion
Aging is associated with significant reductions in fat free mass, and an increase in adiposity. The principal component of the decline in fat free mass is a decrease in muscle mass due to a reduction in muscle protein content and synthesis rates. The loss of FFM is associated with loss of muscle strength and function and with increased disability and mortality (6). The body composition changes in old age are multifactorial and may be related to the concomitant changes in hormone production, protein turnover, and disuse atrophy. The evidence to support the use of testosterone or GH supplementation in age-related sarcopenia is only beginning to be presented. Although testosterone and rhGH can augment lean body mass in older men, we do not know whether the body composition changes during these anabolic interventions are associated with improvements in muscle performance, physical function, and health-related outcomes. Also, most of the data have been generated in healthy, older men with good functional status. The effects of these interventions in the frail elderly and the oldest old have not been demonstrated. The long-term safety of pharmacological interventions such as testosterone and GH has not been established; therefore, the risk to benefit ratio remains uncertain. Research into the possible benefits of nonpharmacological supplements in the elderly is still in its infancy. Undoubtedly, the scientific knowledge has lagged far behind the public and media interest in this issue.
Received June 30, 1999.
Accepted July 2, 1999.
References