David N. Proctor

Exercise and Physical Activity for Older Adults

The purpose of this Position Stand is to provide an overview of issues critical to understanding the importance of exercise and physical activity in older adult populations. The Position Stand is divided into three sections: Section 1 briefly reviews the structural and functional changes that characterize normal human aging, Section 2 considers the extent to which exercise and physical activity can influence the aging process, and Section 3 summarizes the benefits of both long-term exercise and physical activity and shorter-duration exercise programs on health and functional capacity. Although no amount of physical activity can stop the biological aging process, there is evidence that regular exercise can minimize the physiological effects of an otherwise sedentary lifestyle and increase active life expectancy by limiting the development and progression of chronic disease and disabling conditions. There is also emerging evidence for significant psychological and cognitive benefits accruing from regular exercise participation by older adults. Ideally, exercise prescription for older adults should include aerobic exercise, muscle strengthening exercises, and flexibility exercises. The evidence reviewed in this Position Stand is generally consistent with prior American College of Sports Medicine statements on the types and amounts of physical activity recommended for older adults as well as the recently published 2008 Physical Activity Guidelines for Americans. All older adults should engage in regular physical activity and avoid an inactive lifestyle.

Role of nitric oxide in exercise hyperaemia during prolonged rhythmic handgripping in humans.

1. We sought to determine whether the vasodilating molecule nitric oxide (NO) contributes to the forearm hyperaemia observed during prolonged rhythmic handgripping in humans. 2. Two bouts of exercise were performed during experimental protocols conducted on separate days. During each protocol the subject performed a 10 min and a 20 min bout of rhythmic (30 min‐1) handgripping at 15% of maximum. Two exercise bouts were required to facilitate pharmacological interventions during the second protocol. Blood flow in the exercising forearm was measured every minute with plethysmography during brief pauses in the contractions. During both exercise bouts in the first protocol, forearm blood flow increased 2‐ to 3‐fold above rest after 1 min of handgripping and remained constant at that level throughout the exercise. 3. During the 10 min bout of exercise in the second protocol, acetylcholine was given via a brachial artery catheter at 16 micrograms min‐1 for 3 min to evoke NO release from the vascular endothelium. This caused forearm blood flow to increase above the values observed during exercise alone. 4. During the 20 min trial of handgripping in the second protocol, the NO synthase blocker NG‐monomethyl‐L‐arginine (L‐NMMA) was infused in the exercising forearm via the brachial catheter after 5 min of handgripping. The L‐NMMA was infused at 4 mg min‐1 for 10 min. 5. L‐NMMA during exercise caused forearm blood flow to fall to values approximately 20‐30% lower than those observed during exercise alone. When ACh was given during exercise after L‐NMMA administration the rise in blood flow was also blunted, indicating blockade of NO synthase. These data suggest NO plays a role in exercise hyperaemia in humans.

Comparison of techniques to estimate total body skeletal muscle mass in people of different age groups

An estimate of total body muscle mass with dual-energy X-ray absorptiometry (DXA; appendicular muscle mass divided by 0.75) was compared with 24-h urinary creatinine excretion in 59 healthy men and women [20-30 yr (younger), 45-59 yr (middle age), and 60-79 yr (older)] who stayed in a clinical research center for 5 days. Total body water ((2)H(2)O dilution), fat (underwater weighing), bone mineral (DXA), and total body protein mass (based on a 4-compartment model) were also measured. Muscle mass estimates by DXA and creatinine were highly correlated (r = 0.80). However, stepwise multiple regression indicated that a significant amount of additional between-subject variability in DXA-based muscle mass estimates could be explained by total body water. Creatinine excretion, knee extensor strength, and total body protein mass all decreased with age, suggesting a decline in muscle cell mass with aging. However, DXA-based muscle mass and measures of nonfat body mass (i.e., lean body mass by (2)H(2)O and fat-free body mass by underwater weighing) did not change with age. These results indicate that DXA and urinary creatinine excretion give different results regarding the decline in total body muscle mass with aging. The factor(s) responsible for the apparent underestimate of age-related sarcopenia by DXA remain to be fully defined, but changes in body water may be an important contributor.An estimate of total body muscle mass with dual-energy X-ray absorptiometry (DXA; appendicular muscle mass divided by 0.75) was compared with 24-h urinary creatinine excretion in 59 healthy men and women [20-30 yr (younger), 45-59 yr (middle age), and 60-79 yr (older)] who stayed in a clinical research center for 5 days. Total body water (2H2O dilution), fat (underwater weighing), bone mineral (DXA), and total body protein mass (based on a 4-compartment model) were also measured. Muscle mass estimates by DXA and creatinine were highly correlated ( r = 0.80). However, stepwise multiple regression indicated that a significant amount of additional between-subject variability in DXA-based muscle mass estimates could be explained by total body water. Creatinine excretion, knee extensor strength, and total body protein mass all decreased with age, suggesting a decline in muscle cell mass with aging. However, DXA-based muscle mass and measures of nonfat body mass (i.e., lean body mass by2H2O and fat-free body mass by underwater weighing) did not change with age. These results indicate that DXA and urinary creatinine excretion give different results regarding the decline in total body muscle mass with aging. The factor(s) responsible for the apparent underestimate of age-related sarcopenia by DXA remain to be fully defined, but changes in body water may be an important contributor.

Different vasodilator responses of human arms and legs

Forearm vascular responses to intra‐arterial infusions of endothelium‐dependent and ‐independent vasodilators have been thoroughly characterized in humans. While the forearm is a well‐established experimental model for studying human vascular function, it is of limited consequence to systemic cardiovascular control owing to its small muscle mass and blood flow requirements. In the present study we determined whether these responses could be generalized to the leg. Based upon blood pressure differences between the leg and arm during upright posture, we hypothesized that the responsiveness to endothelium‐dependent vasodilators would be greater in the forearm than the leg. Brachial and femoral artery blood flow (Q, ultrasound Doppler) at rest and during intra‐arterial infusions of endothelium‐dependent (acetylcholine and substance P) and ‐independent (sodium nitroprusside) vasodilators were measured in eight healthy men (22–27 years old). Resting blood flows in the forearm before infusion of acetylcholine, substance P or sodium nitroprusside were 25 ± 4, 30 ± 7 and 29 ± 5 ml min−1, respectively, and in the leg were 370 ± 32, 409 ± 62 and 330 ± 30 ml min−1, respectively. At the highest infusion rate of acetylcholine (16 μg (100 ml tissue)−1 min−1) there was a greater (P < 0.05) increase in Q to the forearm (1864 ± 476%) than to the leg (569 ± 86%). Similarly, at the highest infusion rate of substance P (125 pg (100 ml tissue)−1 min−1) there was a greater (P < 0.05) increase in Q to the forearm (911 ± 286%) than to the leg (243 ± 58%). The responses to sodium nitroprusside (1 μg (100 ml tissue)−1 min−1) were also greater (P < 0.05) in the forearm (925 ± 164%) than in the leg (326 ± 65%). These data indicate that vascular responses to both endothelium‐dependent and ‐independent vasodilator agents are blunted in the leg compared to the forearm.

Relative influence of physical activity, muscle mass and strength on bone density.

Abstract: In a population-based sample of 348 men (age 22–90 years) and 351 women (age 21–93 years), we evaluated the relationship of bone density assessed at a variety of skeletal sites by dual-energy X-ray absorptiometry (DXA) with various muscle mass estimates obtained also from the DXA scan and with physical activity by interview and strength assessed both subjectively and objectively. All these parameters declined with age as judged from these cross-sectional data. All estimates of total skeletal muscle mass were strongly correlated with bone density at different skeletal sites. Muscle mass, in turn, was correlated with physical activity and hand strength. In multivariate models including these variables, muscle mass was the strongest determinant of bone density, accounting for 6–53% (mean 27%) of the variance at the different skeletal sites. Physical activity (and/or a physical activity × age interaction) was an independent predictor of bone mass in 48% of the site-specific models and accounted for 0.03–39% (mean 10%) of the variance, while hand strength (and/or a hand strength × age interaction) accounted for up to 4% (mean 1%) of the variance as an independent predictor of bone density in a third of the models. Although these variables together accounted for a large proportion of the variance in bone density, other potential predictors were not assessed in these analyses. The dramatic decline in physical activity over life seemed unable to completely explain the age-related loss of bone mass, and additional research is needed to determine whether the relationship of muscle mass with bone density is a direct one or due instead to other factors such as circulating hormone levels.

Augmented leg vasoconstriction in dynamically exercising older men during acute sympathetic stimulation

Vasoconstrictor responsiveness to acute sympathetic stimulation declines with advancing age in resting skeletal muscle. The purpose of the present study was to determine if age‐related reductions in sympathetic vasoconstrictor responsiveness also occur in exercising skeletal muscle. Thirteen younger (20–30 years) and seven older (62–74 years) healthy non‐endurance‐trained men performed cycle ergometer exercise at ∼60 % of peak oxygen uptake while leg blood flow (femoral vein thermodilution), mean arterial blood pressure (radial artery catheter), and plasma adrenaline and noradrenaline concentrations were measured. After steady state was reached (i.e. ∼4 min), acute sympathetic stimulation was achieved by immersing a hand in ice water for 2–4 min (cold pressor test, CPT). CPT tended to cause a larger increase in mean arterial blood pressure in older men (older (O): 16 ± 3 mmHg; younger (Y): 10 ± 2 mmHg) during exercise, but increases in arterial noradrenaline were similar (O: 2.56 ± 0.96 nM; Y: 1.98 ± 0.40 nM). However, the older men demonstrated a larger percentage reduction in exercising leg vascular conductance (leg blood flow/mean arterial pressure) during CPT compared to younger men (O: ‐13.6 ± 3.1%; Y: ‐1.5 ± 4.3%; P= 0.04). Leg blood flow tended to increase in the younger men, but not in the older men (P= 0.10). These results suggest, in contrast to what has been observed in resting skeletal muscle, that vasoconstrictor responsiveness to sympathetic stimulation is not reduced, but may be augmented in exercising muscle of healthy older humans. This could reflect a reduced ability of local substances (e.g. nitric oxide) to impair vasoconstriction in response to sympathetic stimulation during exercise in older humans.

Age and regional specificity of peak limb vascular conductance in men

Because of methodological variation in previous studies, age-associated changes in peak limb vascular conductance (VC(peak); a functional index of arterial structure) and its determinants remain poorly defined. The objectives of this study were to describe and compare age-associated changes in peak forearm and calf conductance across a broad age range and to identify physiological characteristics that are predictive of variation in limb-specific VC(peak). Peak conductance (plethysmographic flow/brachial mean arterial pressure) of the forearm (forearm VC(peak)) and calf (calf VC(peak)) after 10 min of arterial occlusion was measured twice in 68 healthy, normally active men aged 20-79 yr. Aerobic capacity (cycle peak oxygen consumption), arterial health (ankle-brachial index, pulse wave velocity), and limb-specific measures of muscle mass (dual-energy X-ray absorptiometry) and isometric strength (grip, plantar flexion) were also assessed. The relative decline in forearm VC(peak) with age (-6.6% per decade; P < 0.001) was greater than the decline in calf VC(peak) (-3.4% per decade; P = 0.004). Limb VC(peak) per kilogram of muscle declined with age in the forearm (-3.8% per decade; P = 0.004) but not in the calf (P = 0.35). Age, Vo(2 peak), and regional muscle mass were significant predictors of peak conductance in both limbs; however, these predictors explained considerably less variance in the calf than in the forearm. These results suggest that healthy aging is associated with a linear decline in limb vasodilator capacity in men, but the magnitude of this effect is reduced in the calf relative to the forearm. This could reflect regional differences in habitual muscle use with aging in normally active men.

Evidence for sex differences in cardiovascular aging and adaptive responses to physical activity

There are considerable data addressing sex-related differences in cardiovascular system aging and disease risk/progression. Sex differences in cardiovascular aging are evident during resting conditions, exercise, and other acute physiological challenges (e.g., orthostasis). In conjunction with these sex-related differences—or perhaps even as an underlying cause—the impact of cardiorespiratory fitness and/or physical activity on the aging cardiovascular system also appears to be sex-specific. Potential mechanisms contributing to sex-related differences in cardiovascular aging and adaptability include changes in sex hormones with age as well as sex differences in baseline fitness and the dose of activity needed to elicit cardiovascular adaptations. The purpose of the present paper is thus to review the primary research regarding sex-specific plasticity of the cardiovascular system to fitness and physical activity in older adults. Specifically, the paper will (1) briefly review known sex differences in cardiovascular aging, (2) detail emerging evidence regarding observed cardiovascular outcomes in investigations of exercise and physical activity in older men versus women, (3) explore mechanisms underlying the differing adaptations to exercise and habitual activity in men versus women, and (4) discuss implications of these findings with respect to chronic disease risk and exercise prescription.

Age and sex influence the balance between maximal cardiac output and peripheral vascular reserve

We evaluated the influence of age and sex on the relationship between central and peripheral vasodilatory capacity. Healthy men (19 younger, 12 older) and women (17 younger, 17 older) performed treadmill and knee extensor exercise to fatigue on separate days while maximal cardiac output (Q, acetylene uptake) and peak femoral blood flow (FBF, Doppler ultrasound) were measured, respectively. Maximal Q was reduced with age similarly in men (Y: 23.6 +/- 2.7 vs. O: 17.4 +/- 3.5 l/min; P < 0.05) and women (Y: 17.7 +/- 1.9 vs. O: 12.3 +/- 1.6 l/min; P < 0.05). Peak FBF was similar between younger (Y) and older (O) men (Y: 2.1 +/- 0.5 vs. O: 2.2 +/- 0.7 l/min) but was lower in older women compared with younger women (Y: 1.9 +/- 0.4 vs. O: 1.4 +/- 0.4 l/min; P < 0.05). Maximal Q was positively correlated with peak FBF in men (Y: r = 0.55, O: r = 0.74; P < 0.05) but not in women (Y: r = 0.34, O: r = 0.10). Normalization of cardiac output to appendicular muscle mass and peak FBF to quadriceps mass reduced the correlation between these variables in younger men (r = 0.30), but the significant association remained in older men (r = 0.68; P < 0.05), with no change in women. These data suggest that 1) aerobic capacity is associated with peripheral vascular reserve in men but not women, and 2) aging is accompanied by a more pronounced sex difference in this relationship.

Longitudinal changes in physical functional performance among the oldest old: insight from a study of Swedish twins

Aims and Methods: The primary purpose was to characterize mean and individual-level patterns of change in physical functional performance over eight years (2 year intervals) in a community dwelling sample of Swedish twins (579 men and women aged 79–96 years at baseline). Results: Mixed linear models revealed linear rates of decline for handgrip strength (grip) and time to complete five chair stands, and accelerating decline for peak expiratory flow rate (PEFR) for both sexes. Significant random effects were found for intercept and time for grip and PEFR tests, indicating differences between participants initially and over time. Individual differences in chair-stand performance were significant for initial status only. Age at baseline was predictive of initial status in grip, PEFR and chair performance (women only), but not rate of change. Measures of body size at baseline were predictive of individual variation in initial grip (height), PEFR (weight in men, height in women), and chair performance (height), but had less consistent associations with changes in test performance over time. In the deceased sub-sample (85% of participants), having been further from death was related to less steep declines in grip, but not PEFR or chair performance. Twins from the same pair were related in initial status (twin level variance ∼30–70%), but they were not generally related in rate of change. Conclusions: These results indicate that changes in physical functional performance in an elderly, community-dwelling population vary across individuals in a test-and sex-dependent manner. Constitutional variables (age, sex, body size) are predictive of baseline performance, but explain little variance in change over time. Initial status and rate of change in grip strength had the strongest association with proximity from death, indicating that while PEFR and repeated chair stand time are useful tests to assess function, grip strength appears to be a particularly useful biomarker in the oldest-old.