Dennis R. Taaffe

Sarcopenia: etiology, clinical consequences, intervention, and assessment

The aging process is associated with loss of muscle mass and strength and decline in physical functioning. The term sarcopenia is primarily defined as low level of muscle mass resulting from age-related muscle loss, but its definition is often broadened to include the underlying cellular processes involved in skeletal muscle loss as well as their clinical manifestations. The underlying cellular changes involve weakening of factors promoting muscle anabolism and increased expression of inflammatory factors and other agents which contribute to skeletal muscle catabolism. At the cellular level, these molecular processes are manifested in a loss of muscle fiber cross-sectional area, loss of innervation, and adaptive changes in the proportions of slow and fast motor units in muscle tissue. Ultimately, these alterations translate to bulk changes in muscle mass, strength, and function which lead to reduced physical performance, disability, increased risk of fall-related injury, and, often, frailty. In this review, we summarize current understanding of the mechanisms underlying sarcopenia and age-related changes in muscle tissue morphology and function. We also discuss the resulting long-term outcomes in terms of loss of function, which causes increased risk of musculoskeletal injuries and other morbidities, leading to frailty and loss of independence.

Combined Resistance and Aerobic Exercise Program Reverses Muscle Loss in Men Undergoing Androgen Suppression Therapy for Prostate Cancer Without Bone Metastases: A Randomized Controlled Trial

PURPOSE Androgen suppression therapy (AST) results in musculoskeletal toxicity that reduces physical function and quality of life. This study examined the impact of a combined resistance and aerobic exercise program as a countermeasure to these AST-related toxicities. PATIENTS AND METHODS Between 2007 and 2008, 57 patients with prostate cancer undergoing AST (commenced > 2 months prior) were randomly assigned to a program of resistance and aerobic exercise (n = 29) or usual care (n = 28) for 12 weeks. Primary end points were whole body and regional lean mass. Secondary end points were muscle strength and function, cardiorespiratory capacity, blood biomarkers, and quality of life. RESULTS Analysis of covariance was used to compare outcomes for groups at 12 weeks adjusted for baseline values and potential confounders. Patients undergoing exercise showed an increase in lean mass compared with usual care (total body, P = .047; upper limb, P < .001; lower limb, P = .019) and similarly better muscle strength (P < .01), 6-meter walk time (P = .024), and 6-meter backward walk time (P = .039). Exercise also improved several aspects of quality of life including general health (P = .022) and reduced fatigue (P = .021) and decreased levels of C-reactive protein (P = .008). There were no adverse events during the testing or exercise intervention program. CONCLUSION A relatively brief exposure to exercise significantly improved muscle mass, strength, physical function, and balance in hypogonadal men compared with normal care. The exercise regimen was well tolerated and could be recommended for patients undergoing AST as an effective countermeasure to these common treatment-related adverse effects.

Once-weekly resistance exercise improves muscle strength and neuromuscular performance in older adults

OBJECTIVE: To determine the effect of frequency of resistive training on gain in muscle strength and neuromuscular performance in healthy older adults.

Physical activity, exercise, and inflammatory markers in older adults: Findings from the health, aging and body composition study

Objectives: To examine the association between physical activity and inflammatory markers, with consideration for body fatness and antioxidant use.

High-impact exercise promotes bone gain in well-trained female athletes

Maximizing peak bone mass, as well as reducing its loss after menopause, is important for the prevention of osteoporosis. One mode of activity, gymnastics training, invokes high impact loading strains on the skeleton which may have powerful osteogenic effects. To examine the role of athletic activity, specifically gymnastics, on bone mineral density (BMD) accretion, we monitored longitudinal changes in regional and whole body BMD in collegiate women gymnasts and competitive athletes whose skeletons are exposed to differential loading patterns: runners and swimmers. Two cohorts were studied. Cohort I = 26 gymnasts (19.7 ± 1.2 years), 36 runners (21.1 ± 2.7 years) and 14 nonathletic women (19.3 ± 1.7 years) followed over an 8‐month period. Cohort II = 8 gymnasts (18.9 ± 1.1 years), 11 swimmers (20.0 ± 2.3 years) and 11 nonathletic women (19.0 ± 1.2 years) followed over a 12‐month period. Lumbar spine (L2–4), femoral neck, and whole body BMD (g/cm2) were assessed by dual‐energy X‐ray absorptiometry. For cohort I, the percent change in lumbar spine BMD after 8 months was significantly greater (p = 0.0001) in the gymnasts (2.8 ± 2.4%) than in the runners (−0.2 ± 2.0%) or controls (0.7 ± 1.3%). An increase in femoral neck BMD of 1.6 ± 3.6% in gymnasts was also greater (p < 0.05) than runners (−1.2 ± 3.0%) and approached significance compared with controls (−0.9 ± 2.2%, p = 0.06). For cohort II, gymnasts gained 2.3 ± 1.6% at the lumbar spine which differed significantly (p < 0.01) from changes in swimmers (−0.3 ± 1.5%) and controls (−0.4 ± 1.7%). Similarly, the change at the femoral neck was greater (p < 0.001) in gymnasts (5.0 ± 3.4%) than swimmers (−0.6 ± 2.8%) or controls (2.0 ± 2.3%). The percent change in BMD at any site did not differ between eumenorrheic and irregularly menstruating athletes. These results indicate that bone mineral at clinically relevant sites, the lumbar spine and femoral neck, can respond dramatically to mechanical loading characteristic of gymnastics training in college‐aged women. This occurred despite high initial BMD values and was independent of reproductive hormone status. The results provide evidence to support the view that high impact loading, rather than selection bias, underlies high BMD values characteristic of women gymnasts. Because all athletes underwent resistance training throughout the year of study, muscle strengthening activity did not appear to be a significant factor in the skeletal response observed in gymnasts. We conclude that activities resulting in high skeletal impacts may be particularly osteotropic for young women.

Inflammatory markers are associated with ventilatory limitation and muscle dysfunction in obstructive lung disease in well functioning elderly subjects

Background: Inflammatory markers are increased in chronic obstructive pulmonary disease (COPD) and are hypothesised to play an important part in muscle dysfunction and exercise intolerance. Methods: The Health Aging and Body Composition (Health ABC) study is a prospective observational cohort of well functioning individuals aged 70–79 years. A cross sectional analysis of the baseline data was conducted to examine the association between inflammatory markers and ventilatory limitation, muscle strength, and exercise capacity. These associations were compared in participants with and without obstructive lung disease (OLD). Results: Of the 3075 participants enrolled in the Health ABC cohort, OLD was identified by spirometric testing in 268 participants and 2005 participants had normal spirometric results. Of the participants with OLD, 35%, 38%, and 27% participants had mild, moderate, and severe OLD, respectively. Participants with OLD had lower quadriceps strength (102.5 Nm v 108.9 Nm, p = 0.02), lower maximum inspiratory pressure (64.7 cm H2O v 74.2 cm H2O, p<0.0001), higher systemic interleukin (IL)-6 levels (2.6 pg/ml v 2.2 pg/ml, p<0.0001), and higher C-reactive protein (CRP) levels (3.5 mg/l v 2.5 mg/l, p<0.0001) than those with normal spirometry. In participants with OLD and those with normal spirometry, forced expiratory volume in 1 second (FEV1) was associated with IL-6 (adjusted regression coefficients (β) = −5.3 (95% CI −9.1 to−1.5) and −3.1 (95% CI −4.3 to −1.9), respectively). IL-6 and TNF were also associated with quadriceps strength among participants with OLD and those with normal spirometry (β = −6.4 (95% CI −12.8 to −0.03) and −3.4 (95% CI −5.4 to −1.3), respectively, for IL-6 and β = −10.1 (95% CI −18.7 to −1.5) and −3.8 (95% CI −7 to −0.6), respectively, for TNF). IL-6, quadriceps strength, and maximum inspiratory pressures were independent predictors of reduced exercise capacity in both groups. Conclusions: In well functioning elderly subjects with or without OLD, IL-6 is associated with reduced FEV1, quadriceps strength, and exercise capacity.

Race and sex effects on the association between muscle strength, soft tissue, and bone mineral density in healthy elders : the health, aging, and body composition study

Two factors generally reported to influence bone density are body composition and muscle strength. However, it is unclear if these relationships are consistent across race and sex, especially in older persons. If differences do exist by race and/or sex, then strategies to maintain bone mass or minimize bone loss in older adults may need to be modified accordingly. Therefore, we examined the independent effects of bone mineral‐free lean mass (LM), fat mass (FM), and muscle strength on regional and whole body bone mineral density (BMD) in a cohort of 2619 well‐functioning older adults participating in the Health, Aging, and Body Composition (Health ABC) Study with complete measures. Participants included 738 white women, 599 black women, 827 white men, and 455 black men aged 70‐79 years. BMD (g/cm2) of the femoral neck, whole body, upper and lower limb, and whole body and upper limb bone mineral‐free LM and FM was assessed by dual‐energy X‐ray absorptiometry (DXA). Handgrip strength and knee extensor torque were determined by dynamometry. In analyses stratified by race and sex and adjusted for a number of confounders, LM was a significant (p < 0.001) determinant of BMD, except in white women for the lower limb and whole body. In women, FM also was an independent contributor to BMD at the femoral neck, and both FM and muscle strength contributed to limb BMD. The following were the respective β‐weights (regression coefficients for standardized data, Std β) and percent difference in BMD per unit (7.5 kg) LM: femoral neck, 0.202‐0.386 and 4.7‐5.9%; lower limb, 0.209‐0.357 and 2.9‐3.5%; whole body, 0.239‐0.484 and 3.0‐4.7%; and upper limb (unit = 0.5 kg), 0.231‐0.407 and 3.1‐3.4%. Adjusting for bone size (bone mineral apparent density [BMAD]) or body size BMD/height) diminished the importance of LM, and the contributory effect of FM became more pronounced. These results indicate that LM and FM were associated with bone mineral depending on the bone site and bone index used. Where differences did occur, they were primarily by sex not race. To preserve BMD, maintaining or increasing LM in the elderly would appear to be an appropriate strategy, regardless of race or sex.

Effects of hormone replacement therapy and high-impact physical exercise on skeletal muscle in post-menopausal women: a randomized placebo-controlled study.

An age-related decline in muscle performance is a known risk factor for falling, fracture and disability. In women, a clear deterioration is observed from early menopause. The effect of hormone replacement therapy (HRT) in preserving muscle performance is, however, unclear. This trial examined the effects of a 12-month HRT and high-impact physical exercise regimen on skeletal muscle in women in early menopause. A total of 80 women aged 50-57 years were assigned randomly to one of four groups: exercise (Ex), HRT, exercise+HRT (ExHRT) and control (Co). The exercise groups participated in a high-impact training programme. The administration of HRT (oestradiol/noretisterone acetate) or placebo was carried out double-blind. Knee extension torque and vertical jumping height were evaluated. Lean tissue cross-sectional area (LCSA) and the relative proportion of fat within the muscle compartment were measured for the quadriceps and lower leg muscles. The ExHRT group showed significant increases in knee extension torque (8.3%) and vertical jumping height (17.2%) when compared with the Co group (-7.2%). Vertical jumping height also increased after HRT alone (6.8%). The LCSA of the quadriceps was increased significantly in the HRT (6.3%) and ExHRT (7.1%) groups when compared with the Ex (2.2%) and Co (0.7%) groups. Lower leg LCSA was also increased in the ExHRT group (9.1%) when compared with the Ex (3.0%) and Co (4.1%) groups. In addition, the increase in the relative proportion of fat in the quadriceps in the Co group (16.6%) was significant compared with those in the HRT (4.9%) and ExHRT (-0.6%) groups. Thus, in post-menopausal women, muscle performance, muscle mass and muscle composition are improved by HRT. The beneficial effects of HRT combined with high-impact physical training may exceed those of HRT alone.

Resistance exercise dosage in older adults : Single- versus multiset effects on physical performance and body composition

Objectives: To determine whether variation in resistance exercise volume affects muscle function and physical performance response in older adults.

Improved Physical Performance in Older Adults Undertaking a Short-Term Programme of High-Velocity Resistance Training

Background: The age-related loss of muscle power in older adults is greater than that of muscle strength and is associated with a decline in physical performance. Objective: To investigate the effects of a short-term high-velocity varied resistance training programme on physical performance in healthy community-dwelling adults aged 60–80 years. Methods: Subjects undertook exercise (EX; n = 15) or maintained customary activity (controls, CON; n = 10) for 8 weeks. The EX group trained 2 days/week using machine weights for three sets of eight repetitions at 35, 55, and 75% of their one-repetition maximum (the maximal weight that an individual can lift once with acceptable form) for seven upper- and lower-body exercises using explosive concentric movements. Results: Fourteen EX and 10 CON subjects completed the study. Dynamic muscle strength significantly increased (p = 0.001) in the EX group for all exercises (from 21.4 ± 9.6 to 82.0 ± 59.2%, mean ± SD) following training, as did knee extension power (p < 0.01). Significant improvement occurred for the EX group in the floor rise to standing (10.4 ± 11.5%, p = 0.004), usual 6-metre walk (6.6 ± 8.2%, p = 0.010), repeated chair rise (10.4 ± 15.6%, p = 0.013), and lift and reach (25.6 ± 12.1%, p = 0.002) performance tasks but not in the CON group. Conclusions: Progressive resistance training that incorporates rapid rate-of-force development movements may be safely undertaken in healthy older adults and results in significant gains in muscle strength, muscle power, and physical performance. Such improvements could prolong functional independence and improve the quality of life.