Physiological aging is associated with physical inactivity and contributes to functional or physical deterioration and age-related morbidity. Habitual physical activities appear to provide an antiaging influence, which has been previously reported to prevent age-related decreases in aerobic capacity (1,5,17,21) and improves cardiac reserve (14) and vascular function during exercise (4). However, despite improvement in the cardiovascular and respiratory function associated with aerobic exercise training, cross-sectional comparisons of aerobically trained high fit young adults have demonstrated a reduction in orthostatic tolerance (OT) simulated by lower-body negative pressure (LBNP) (10,22,31). Physiological mechanisms identified with the high incidence of orthostatic intolerance (OIT) observed in endurance exercise-trained young adults include the following: (i) an attenuated vasoconstrictor response to central hypovolemia (13,31), (ii) an enhanced cardiac compliance (10) that diminishes cardiac compensatory response during orthostatic challenge, and (iii) a reduced arterial baroreflex sensitivity (22). In young healthy adults, these physiological adaptive changes in cardiovascular function (CVF) result in OIT especially when rapidly rising from a supine to an upright posture (32). However, the question remains as to whether a longitudinal aerobic exercise training program for older adults would similarly result in OIT. Such a result (10,22,31) would compromise the beneficial influence of exercise training on the elderly's abilities to transfer from supine to upright posture.
It is generally accepted that endurance-trained young adult with maximal O2 uptakes (V˙O2max) ≥60 mL·min−1·kg−1 and/or deconditioned young adults (after bed rest or spaceflight) have a reduced OT (9). OIT in relation to aerobic fitness has been characterized to be in the form of a “U,” in which the highest OT is located at the center or nadir of a U-shaped curve relating OIT from low to high V˙O2max (9). Aerobic exercise training in young adults, who have improved their V˙O2max to ≥60 mL·min−1·kg−1, will increase their incidence of OIT by relocating their V˙O2max from the nadir to the right end of the U-shaped curve. By contrast, aging is normally accompanied by cardiovascular deconditioning, which predisposes the elderly adults' V˙O2max to be associated with the left end of the U-shaped curve. We hypothesized that the physiological adaptations associated with aerobic exercise training of elderly untrained adults would result in an increase in V˙O2max that will move them nearer to the nadir of the OIT/V˙O2max relationship and result in an increase in OT. The purpose of the present study was to examine the effect of aerobic exercise training on changes in peak aerobic capacity and the cardiovascular response to orthostatic stress.
Four men and four women (67.0 ± 1.7 yr old) voluntarily participated in the study after having provided informed consent and were medically approved to participate in the study (Table 1). All subjects had well-controlled arterial blood pressure (ABP) (≤140/90 mm Hg) and were free of metabolic, renal, or pulmonary diseases. None of the subjects had engaged in any regular physical exercise training program before the study. The experimental protocol was reviewed and approved by the Institutional Review Board for the Protection of Human Subjects at the University of North Texas Health Science Center at Fort Worth. After having passed the medical screening examination, each of the subjects scheduled an orientation visit to familiarize them to the study procedures and measurements in the laboratory. A total of 10 subjects began the exercise training program, but two of them did not complete the 1-yr exercise training program.
The aerobic training program consisted of cycling on a stationary bicycle or walk-jogging on a motor-driven treadmill at work intensities that elevated their HR to 65%–75% of the individual's HRpeak, approximately between 105 and 115 bpm, with a cumulative exercise time ≥60 min per session for 3 d·wk−1 for 1 yr. During exercise sessions, the subjects wore an HR monitor strapped around the chest along with a wristwatch-like display (Polar Electro, Kempele, Finland), and the heartbeats were constantly monitored for feedback. During the initial 3 to 4 wk of exercise training, the training sessions were supervised by a research assistant or technician. During these sessions, the subjects became familiar with the process of wearing HR monitoring and adjusting exercise equipment. Most of exercise sessions took place in the gyms or health clubs located on the subjects' living complex or in the neighborhood. The research assistants made frequent telephone calls and/or site visits to keep contact with the subjects to address their questions and to ensure them to keep their exercise training routine. Every 3 months during the training, the subjects visited the laboratory to undergo a graded exercise stress test to measure their peak O2 uptakes (V˙O2peak) and HRpeak.
Graded maximal exercise stress test was performed on an upright stationary bicycle (SciFit, Tulsa, OK) during which the subject wore a disposable air-cushioned mask. The subject's breath-by-breath ventilation variables and O2 uptake (VacuMed Vista V˙O2 Lab, Ventura, CA) along with HR obtained from 12 leads of ECG were continuously monitored and averaged every 15 s by a computer. Before the maximal stress test, the subject had a warm-up with the cycling resistance gradually (~1 min) increased to a level that elevated the HR between 105 and 115 bpm. After a 5-min recovery from the warm-up exercise, the subject started the graded exercise stress test with an initial workload of 60 cycles per min. The workload was increased every 2 min (10–25 W each increment with an increase in HR approximating +10 bpm) until V˙O2peak. The V˙O2peak was determined by (i) a plateau in O2 uptake that occurred at or near the peak work output, (ii) a respiratory quotient ≥1.1; and/or the subject's volitional fatigue, i.e., unable to keep the cycling cadency. A coefficient of variance 3.47% was observed from three repeated measurements of V˙O2peak within 2 wk on one subject near the end of his exercise training program.
Before and after the 1-yr aerobic exercise training program, cardiovascular response to OT was tested using LBNP graded from −10 through −15, −20, −30, −40, and −50 mm Hg, for 6 min for each negative pressure of LBNP, while the subject lay in a supine position with the lower-body sealed within an LBNP chamber (6,27,29,34). After the subject relaxed in the supine position for ≥15 min, baseline HR, systolic blood pressure (SBP), DBP, systemic arterial oxygen saturation (SaO2), and regional cerebral tissue oxygenation (ScO2) were continuously monitored for ~5 min followed by the application of graded LBNP (Fig. 1). During the test, LBNP application was terminated immediately whenever the subject's (i) SBP was decreased to ≤90 mm Hg, (ii) diastolic blood pressure (DBP) ≤60 mm Hg, (iii) HR decreased instead of increasing, and (iv) the subject requested to stop or the subject seemed to be presyncopal, such as lightheadedness and/or weakness. During the experiment, pressure inside the LBNP box was continuously monitored by a pressure transducer (Model DP45; Validyne Engineering, Northridge, CA), see Figure 1. The cumulative stress index (CSI) was calculated as the product of the LBNP intensity and the time completed expressed in millimeters of mercury per minute (20). All variables were recorded by a computer interfaced through a data acquisition system (BIOPAC MP150, Santa Barbara, CA). HR was monitored from a standard lead of ECG (BIOPAC ECG100C). Beat-to-beat SBP and DBP were measured by a tonometer (Colin 7000 Tonometer, San Antonio, TX) placed on the subject's right wrist. Mean arterial pressure (MAP) was calculated from the sum of 1/3 of SBP and 2/3 of DBP. Arterial blood pressure measured using the tonometry has been found to be highly correlated with directly measured ABP via intraradial arterial catheter in our laboratory (33) and by others (24). SaO2 was monitored using finger oximetry (BIOPAC OXY100C), and prefrontal ScO2 was determined by a near-infrared spectroscopic sensor (4100 INVOS Cerebral Oximeter, Somanetics, Troy, MI) placed on the subject's right forehead.
Before the LBNP tolerance test, carotid baroreceptor reflex (CBR) function at supine resting state was assessed and compared before and after aerobic exercise training (four men and two women). Five-second pulses of neck pressure (+40 and +20 mm Hg) and neck suction (−20, −40, −60, and −80 mm Hg) were delivered in random order to a malleable lead neck chamber that encompassed the carotid sinus region of the subject's anterior portion of the neck (16,18) while the subjects held their breath at the end of normal expiration (28), i.e., the functional residual capacity. In addition, baseline HR and MAP were obtained during breath holding at the functional residual capacity without the application of neck pressure or suction. The duration and timing of delivery of neck pressure or suction controlled by a computer with custom-made software as described previously (18,28). This brief 5-s pulses of neck pressure and suction, as applied in the present study, selectively elicit the CBR response with minimal or no influence from aortic arterial baroreceptor reflex response (16). Change in carotid sinus pressure (CSP) was estimated from the difference between baseline MAP and neck chamber pressure or suction delivered (18,19). Along with the baseline HR and MAP, their peak responses to the changes in CSP during the application of neck pressure and suction were selected to plot as the CBR mediated cardiac (CBR-HR) and vasomotor (CBR-MAP) responsiveness, respectively (Fig. 2).
Group CBR stimulus–response curve (n = 6) was plotted using the HR and the MAP against the estimated CSP (ECSP) during neck pressure and suction from +40, +20, 0, −20, −40, −60, and −80 mm Hg (Fig. 2). A four-parameter logistic model was used to fit CBR-HR and CBR-MAP stimulus–response curves (18) and to derive the CBR gains for the HR and MAP responsiveness (2), respectively. Maximal gain, i.e., change in variable (HR or MAP) per change in ECSP or (G max), occurs at the steepest slope of the sigmoidal stimulus–response curve (i.e., ΔHR/ΔECSP or ΔMAP/ΔECSP) was identified as the maximal sensitivity of the CBR control of HR or MAP (16,18), respectively.
During the LBNP test, 1-min continuous representative data of HR, SBP, DBP, SaO2, and ScO2 at rest (LBNP = 0 mm Hg) and from each completed LBNP were selected and averaged as the baseline data and the response data to LBNP, respectively. Before the syncope, a section of 15-s continuous data before the termination of LBNP application was selected and averaged as the presyncopal response. All data were reported as group mean ± SE of the mean. In addition, relative changes (%) from the baseline (i.e., LBNP = 0) were assessed and compared.
A two-way ANOVA was applied to test LBNP factor and training factor for HR, ABP, SaO2, and ScO2. The procedure with Tukey option was applied for post hoc repeated-measures analysis if the main factor was significant. A paired t-test was applied to compare the difference in baseline physiological or physical variables before and after aerobic exercise training. A P value ≤0.05 was considered statistically significant. The software package Statistical Analysis System (SAS version 9.3, Gary, NC) was used for the data analyses and significance testing.
Regular aerobic physical activities of moderate intensity and frequency increased V˙O2peak by +22% ± 2% (P < 0.001), peak work output by +17% ± 3% (P < 0.001), and HRpeak by +3% ± 1% (P = 0.019) in previously physically inactive elderly adults (Table 1). After 1 yr of exercise training, resting HR was decreased by −5.7 ± 1.7 bpm (P = 0.013) or −8.5% ± 2.5%, whereas MAP, SBP, and DBP were decreased by −12 ± 2 mm Hg (P = 0.002) or −11% ± 2%, by −11 ± 2 mm Hg (P = 0.001) or −8% ± 1%, and by −12 ± 3 mm Hg (P = 0.007) or −14% ± 4%, respectively (Table 2). The CBR-HR G max was significantly increased from −0.129 ± 0.023 bpm·mm Hg−1 pretraining to −0.269 ± 0.035 bpm·mm Hg−1 posttraining (P = 0.010). However, the CBR-MAP G max was not different before (−0.346 ± 0.088 mm Hg·mm Hg−1) and after (−0.435 ± 0.155 mm Hg·mm Hg−1) exercise training. Overall, both CBR-HR and CBR-MAP stimulus–response curves along with the operating point moved leftward to a lower threshold of the CBR operational range after exercise training (Fig. 2). This leftward and downward resetting of the operating point (OP) pressure was most likely because of the training-induced lower baseline arterial pressures and HR. Before exercise training, five of the eight elderly subjects (three women) did not complete the graded LBNP tolerance test. After exercise training, only one woman subject was unable to complete the LBNP protocol (Fig. 3). However, even this subject also increased her LBNP tolerance. After the exercise training program, the group's CSI (n = 8) was increased (P = 0.025) from 767 ± 68 mm Hg·min−1 pretraining to 946 ± 44 mm Hg·min−1 posttraining (+23%). As there were no sex-related differences in the increases in CSI or V˙O2peak, the data obtained from both genders were analyzed as one group of subjects. The group HR increased (P = 0.001) with the graded LBNP application (Table 2), which were significantly above the baseline during −40 and −50 mm Hg LBNP (Fig. 4). SBP decreased significantly (P = 0.046) during LBNP (Table 2). Before exercise training, decreases in group SBP were significant at −40 mm Hg LBNP (−8%, n = 7) and at presyncope (−27%, n = 5). After exercise training, a significant decrease in group SBP (n = 7) was observed only at −50 mm Hg LBNP (−12%). Although systemic oxygen saturation was maintained throughout the graded LBNP application, ScO2 decreased (P = 0.045) with increases in LBNP (Table 2). A decrease in ScO2 from baseline (0 mm Hg LBNP) became significant at LBNP −40 mm Hg (−5%) pretraining, whereas it became significant at LBNP −50 mm Hg (−7%) after training, see Figure 4. At presyncope before exercise training, a 13% decrease in group ScO2 (n = 5) was observed.
Our data indicate that prolonged moderate intensity and frequency of aerobic exercise training of sedentary elderly adults results in (i) an increase in aerobic capacity, (ii) an increase in exercise performance, (iii) a lower resting HR and ABP, and (iv) an increase in OT of five subjects who failed to complete an LBNP tolerance test before exercise training. The finding of an increased OT is in marked contrast to the reduced OT observed in endurance-trained young adults (10,22,31).
In general, as we age, we become more sedentary, resulting in an age-related decline in aerobic capacity that is primarily a result of detraining (21). Bed rest deconditioning without exercise training countermeasures, which are often found in residents of long-term care facilities, exacerbates the detraining effect of sedentary living and results in cardiovascular deconditioning and decreased blood volume (11,23). In the 1990s, it became evident that the relationship between OIT and aerobic fitness was a nonlinear shallow “U” shape with a high incidence of OIT associated with a low aerobic fitness of <30 mL O2·kg−1·min−1 V˙O2max and paradoxically is also associated with a high aerobic fitness of >55–60 mL O2·kg−1·min−1 V˙O2max (3,9). Hence, one possible explanation for the improved OT of the elderly subjects after exercise training in the present study is the fact that the exercise training program induced changes in CVF associated with the increase in V˙O2peak that moved the CVF/ V˙O2peak relationship toward the nadir of the shallow “U” resulting in an increase in OT (9). Indeed when exercise training was performed by subjects that increased their V˙O2max by 20% but remained less than 55–60 mL O2·kg−1·min−1, their tolerance to LBNP was increased by 28% (3).
In our earlier cross-sectional (25,26,30) and longitudinal (31) investigations of young adults, we identified that endurance exercise training resulted in a reduced baroreflex control of HR. Subsequently, Levine et al. (10) and Mack et al. (12) identified that endurance training programs in young adults resulted in increases in resting blood volume, stroke volume, and cardiac compliance. These adaptations resulted in the exercise-trained subjects having steeper Starling curves and slower HR than the untrained subjects. The training-induced increased slope of the Starling curves resulted in greater drops in stroke volume per unit decrease in pulmonary capillary wedge pressure (ΔSV/ΔPCWP) and an earlier onset of LBNP-induced OIT. Thus, the effects of the HR change on blood pressure regulation during LBNP depended on stroke volume and blood flow rather than reflex control of HR (10).
In the present study, the endurance exercise training program reduced resting MAP, i.e., the operating point (OP) pressure without a change in G max − ΔMAP/ΔECSP, or sensitivity, of the carotid–vasomotor baroreflex. By contrast, the carotid–cardiac baroreflex control of HR, i.e., G max − ΔHR/ΔECSP, or sensitivity, increased 100%. Previously, Levine's group investigated the question whether a 1-yr endurance exercise training program (similar to the present study) of healthy but sedentary lifestyle subjects ≥65 yr would reverse the age-related cardiovascular stiffening and result in a masters athlete phenotype (7). One year of endurance exercise training failed to increase cardiac compliance (ΔSV/ΔPCWP). However, the training program did result in increases in V˙O2max, arterial function, and left ventricular remodeling. Unfortunately, no assessment of baroreflex control of the heart or the vasculature was obtained (7). However, Convertino's (3) review of longitudinal and cross-sectional studies indicated that exercise training did not compromise baroreflex control of HR or vasomotion. In Convertino's review, many of the investigations summarized in the review involved training young adult subjects with V˙O2max values between 40 and 50 mL O2·min−1·kg−1 (3), whereas in the present study, the elderly subjects increased their V˙O2peak from 22.8 ± 0.9 to 27.9 ± 1.3 mL O2·min−1·kg−1. These V˙O2peak values are consistent with the sedentary cross-sectional age-related population values (7).
It is well established that in healthy subjects, LBNP from 0 to −20 mm Hg do not change ABP and HR (13), although right atrial pressure (8) and/or central venous pressure (35) are usually decreased, indicating a presence of central hypovolemia. Thus, the mild decrease in cardiac output during 0 to −20 mm Hg LBNP is compensated for by a reflexive vasoconstriction, which maintains ABP constant without significant increases in HR. Our data confirmed that there was no systemic hypotension or significant increase in HR during mild LBNP in elderly subjects before and after exercise training (Fig. 4). However, when LBNP reached −40 mm Hg in both the pre- and the posttraining states, HR values were significantly increased in association with a tendency toward systemic hypotension. However, five of our subjects before exercise training did not complete the graded LBNP test up to −50 mm Hg and had a precipitous decrease in ABP with a vasovagal response. Three of the pretrained subjects tolerated −50 mm Hg LBNP and had a significant increase in HR without further systemic hypotension. These data confirmed that a reflexive increase in vasomotor tone or vasoconstriction was critical to maintain ABP during LBNP, whereas the reflexive cardiac response helped maintain ABP by increasing the contribution of the cardiac output (15).
We have previously identified that the increased vascular resistance during LBNP reduces brain perfusion and results in a decrease in cerebral oxygenation (ScO2) (6). In the present study, a significant decrease in ScO2 was observed at −40 mm Hg LBNP in elderly subjects before aerobic exercise training (Fig. 4). After aerobic exercise training, ScO2 at −40 mm Hg LBNP was maintained, whereas it was significantly decreased when LBNP reached −50 mm Hg (Fig. 4). These data suggest that aerobic exercise training in previously sedentary elderly adults enabled the ScO2 to be maintained stable during LBNP-induced central hypovolemia. Furthermore, the increased carotid–HR reflex sensitivity and the increased contribution of the cardiac output to the maintenance of ABP we have identified, along with the reported increases in total blood volume (4,12), were factors in maintaining ScO2 during the LBNP challenge (6).
The present study confirms that healthy sedentary adults even in their 6th or 7th decade of life can improve their aerobic fitness and physical work output. These findings identify that one is never too old to benefit from aerobic physical exercise. For elderly adults who have a low OT, or sensitive to postural changes from supine to upright, chronic aerobic exercise improves not only the functions of cardiorespiratory and skeletal muscle systems but also orthostatic stability. These adaptive changes provide a physiological basis for regular aerobic physical activities to help prevent elderly from falling, lightheadedness, or dizziness during postural transfer and/or sustained upright posture.
In conclusion, the findings of the present study identify that aerobic exercise training for previously sedentary elderly individuals improves their tolerance to exercise and orthostatic stress. An improved exercise tolerance may be attributable to an enhanced cardiac reserve evident by a lower resting HR combined with an increased HRpeak, whereas an improved OT is likely a result of an enhanced carotid–HR reflex sensitivity with a subsequent improvement in cerebral tissue oxygen delivery during central hypovolemia.
The authors thank the volunteer subjects for their cheerful cooperation during the study. They also thank Frederick Schaller, D.O., and Karen Cox, R.N., for their help with the subjects' physical screening and Hong Guo and Patrick Chanthavong for their assistance during the subjects' exercise training and data collection. Funding for XS was provided by an Investigator Grant from the Texas Alzheimer's Research and Care Consortium and a Pilot Trial Award from the Center for Alzheimer's and Neurodegenerative Disease Research, University of North Texas Health Science Center. D. X. was supported by a Fujian Province grant FJ2016B172 and H. W. was supported by the governmental scholarship of China.
The results of the present study do not constitute endorsement by the American College of Sports Medicine. The results of the study are presented clearly, honestly, and without fabrication, falsification, or inappropriate data manipulation.
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