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Ischemic skeletal muscle conditions are known to augment exercise-induced increases in blood pressure (BP). Aging is also a factor that enhances the pressor response to exercise. However, the effects of aging on the BP response to ischemic exercise remain unclear. We, therefore, tested the hypothesis that aging enhances the BP response to rhythmic handgrip (RHG) exercise during postexercise muscle ischemia (PEMI). We divided the normotensive participants without cardiovascular diseases into three age groups: young (n = 26; age, 18-28 years), middle-aged (n = 23; age, 35-59 years), and older adults (n = 23; age, 60-80 years). The participants performed RHG exercise with minimal effort for 1 min after rest with and without PEMI, which was induced by inflating a cuff on the upper arm just before the isometric handgrip exercise ended; the intensity was 30% of maximal voluntary contraction force. Under PEMI, the increase in diastolic BP (DBP) from rest to RHG exercise in the older adult group (Δ13 ± 2 mmHg) was significantly higher than that in the young (Δ5 ± 2 mmHg) and middle-aged groups (Δ6 ± 1 mmHg), despite there being no significant difference between the groups in the DBP response from rest to RHG exercise without PEMI. Importantly, based on multiple regression analysis, age remained a significant independent determinant of both the SBP and DBP responses to RHG exercise during PEMI (p < 0.01). These findings indicate that aging enhances the pressor response to ischemic rhythmic exercise., (© 2021 The Authors. Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.)

Increased arterial stiffness has emerged as a strong predictor of future cardiovascular events and all-cause mortality. The aim of this study was to elucidate influences of endothelin (ET)-related genetic polymorphisms and regular physical activity on age-related arterial stiffening through a 10-yr longitudinal study. A decadal change in brachial-ankle pulse wave velocity (baPWV), an index of arterial stiffness, was evaluated retrospectively among 92 volunteers (63 ± 14 yr, 51 men). The targeted single-nucleotide polymorphisms were ET-A receptor SNP rs5333 (ET-A) and ET-B receptor SNP rs5351 (ET-B). Subjects with either ET-A TC or CC genotypes exhibited significantly greater increases in baPWV (+15.3 ± 11.7 and +16.6 ± 15.7%/dec, respectively) than ET-A TT genotype holders (+9.2 ± 9.0%/dec), whereas subjects with the ET-B GG genotype showed a significantly greater increase in baPWV (+17.7 ± 14.1%/dec) than other ET-B genotype holders (AA: +9.5 ± 10.0%/dec; AG: +11.2 ± 9.6%/dec). The combination of these ET-related genetic risks was associated with a 2.4 times greater decadal increase in baPWV compared with no genetic risk (+8.1 ± 8.4 vs. 19.5 ± 16.0%/dec). In contrast, individuals engaging in >15 METs·h/wk of aerobic exercise showed substantially smaller increases in baPWV (+5.0 ± 9.7%/dec) compared with their physically inactive peers (approximately +13%/dec). These differences remained significant after adjusting for confounding factors, including baseline baPWV and ET-related genotype risk. Our current longitudinal study found that ET-related gene polymorphisms contribute to diverse age-related changes in arterial stiffness, and that regular sufficient aerobic exercise attenuates the age-related arterial stiffening independently of ET-related gene polymorphisms. NEW & NOTEWORTHY This 10-yr longitudinal study suggests that endothelin-related gene polymorphisms contribute to divergent increases in arterial stiffness with advancing age, whereas regular sufficient aerobic exercise attenuates age-related arterial stiffening independently of ET-related gene polymorphisms. This notion partly supports prevailing evidence that regular aerobic exercise contributes to a lower incidence of cardiovascular disease.

An early return of reflected waves, the backward propagation of the arterial pressure wave from the periphery to the heart, is associated with the augmentation of central pulse pressure and cardiovascular risks. The locations of arterial pressure wave reflection, along with arterial stiffening, have a major influence on the timing of the reflected wave. To determine the influence of aging on the location of a major reflection site, arterial length (via 3D artery tracing of MRI) and central (carotid-femoral) and peripheral (femoral-ankle) pulse wave velocities were measured in 208 adults varying in age. The major reflection site was detected by carotid-femoral pulse wave velocity and the reflected wave transit time (via carotid arterial pressure wave analysis). The length from the aortic valve to the major reflection site (eg, effective reflecting length) significantly increased with aging. The effective reflecting length normalized by the arterial length demonstrated that the major reflection sites were located between the aortic bifurcation and femoral site in most of the subjects. The normalized effective reflecting length did not alter with aging until 65 years of age and increased remarkably thereafter in men and women. The effective reflecting length was significantly and positively associated with the difference between central and peripheral pulse wave velocities (r=0.76). This correlation remained significant even when the influence of aortic pulse wave velocity was partial out (r=0.35). These results suggest that the major reflection site shifts distally with aging partly because of the closer matching of impedance provided by central and peripheral arterial stiffness.

Objectives: To determine whether human aorta lengthens with aging and to evaluate the impact of the hypothesized aortic elongation on pulse wave velocity (PWV) measurements., Background: Although it is generally thought that the aorta becomes tortuous with aging, there has been no systematic study to date in healthy adults to determine if this is so. Such age-related aortic elongation may be a confounding factor for the PWV measurement in elderly people., Methods: Arterial lengths were computed by the 3-dimensional transverse magnetic resonance image arterial tracing of the aorta and carotid and iliac arteries in 256 apparently healthy adults (age 19 to 79 years)., Results: The ascending aorta was greater with advancing age (r = 0.72), whereas the lengths of the descending aorta and carotid and iliac arteries were not associated with age. The elongation of the ascending aorta was associated with the corresponding increases in aortic PWV (beta = 0.50) and brachial/aortic pulse pressure ratio (beta = 0.24), which is an index of pulse wave amplification. The straight distance between carotid and femoral sites (car-fem), the most popular arterial length measurement, overestimated the aortic length measured with the magnetic resonance image by approximately 25%. The most accurate arterial length estimation was the distance obtained by subtracting carotid length from the car-fem, with <5% difference from the magnetic resonance image-measured length. Because the ascending aorta was omitted or subtracted from the length estimation in PWV, the impact of age-related elongation of the aorta on PWV was small., Conclusions: The aorta lengthens with age, even in healthy humans, due primarily to the elongation of the ascending aorta. Age-related aortic elongation has little impact on PWV measurements, as the ascending aorta, which undergoes lengthening with age, is not included in the arterial length measurements.

An increase in arterial stiffness with advancing age is associated with several pathological states, including hypertension and arteriosclerosis. Regular exercise improves the aging-induced increase in arterial stiffness and has a protective effect against these diseases. However, not all individuals respond to exercise to the same extent. Atrial natriuretic peptide (ANP) is involved in the regulation of basal blood pressure, blood flow, and vascular tone. The present study was designed to clarify whether gene polymorphisms in ANP-related genes affect exercise-induced improvements in arterial stiffness. We performed a cross-sectional study of 291 healthy middle-aged and older Japanese subjects (63+/-1 years), examining the relationship between daily physical activity-induced improvements in arterial stiffness, estimated by brachial-ankle arterial pulse wave velocity (baPWV), and the gene polymorphisms of valine32methionine (V32M: 664G>A) in exon 1 of ANP and asparagine521aspartic acid (N521D: 1780A>G) in exon 8 of the ANP clearance receptor (NPR-C). The baseline baPWV was significantly lower in the active group, but no differences were seen in blood pressure. Active subjects with the ANP-VV genotype had significantly lower baPWV and higher plasma ANP levels compared with inactive subjects, but there were no variations related to the VM+MM genotype. Additionally, baPWV and plasma ANP levels were negatively correlated in ANP-VV genotype subjects, but were not correlated in VM+MM individuals. Our results suggest that ANP polymorphism in older Japanese subjects may affect the cardiovascular response to regular exercise.

Background: Increased arterial stiffness is an independent risk factor for cardiovascular disease. The estrogen system (estrogen and estrogen receptor-alpha [ER-alpha]) has potent vasodilator and antiatherosclerotic activity in vascular tissue and therefore was implicated in the regulation of arterial stiffness. We hypothesized that the relationship between arterial stiffness and gene polymorphisms in ER-alpha has a sex-specific component in older humans., Methods: Two hundred healthy older subjects, comprised of 85 men and 115 postmenopausal women (men, 66 +/- 5 years old; women, 64 +/- 7 years old; mean +/- SD) participated in a cross-sectional study. We determined the genotypes of single-nucleotide polymorphisms (SNPs) at -401T/C of intron 1 and at 30T/C of exon 1 of ER-alpha, using a TaqMan-polymerase chain reaction method. Arterial stiffness was estimated by brachial-ankle pulse-wave velocity (baPWV)., Results: Polymorphisms of both -401T/C and 30T/C in ER-alpha affected baPWV values in postmenopausal women but did not affect men. The baPWV in women was significantly lower in the CC genotype at both -401T/C and 30T/C than in the TT genotype (both P < .05), and the CC genotype of two SNPs in women was significantly lower than in men., Conclusions: The present study suggests that the relationship between arterial stiffness and -401T/C or 30T/C polymorphisms in ER-alpha is different between sexes in older humans. These polymorphisms may be important in the health and clinical care of cardiovascular function and disease in older women.

A decrease in systemic arterial compliance (SAC) increases left ventricular load along with the demand for excessive myocardial oxygen consumption when the age-related reduction of SAC reaches a marked level, and consequently may depress left ventricular pump function. Reduced left ventricular pump function decreases aerobic capacity, and some study groups have shown that SAC and/or central arterial distensibility is correlated with maximal aerobic capacity in humans. We thus hypothesize that, once the age-related reduction of SAC reaches a marked level, the participation of SAC in aerobic capacity will be significant even during sub-maximal exercise. Thirty young humans and 46 elderly humans participated in this study. SAC, oxygen uptake at the ventilatory threshold (VO2VT), and the ratio of increase in oxygen uptake, in cardiac output, and in effective arterial elastance to increase in work rate (deltaVO2/deltaWR, deltaCO/deltaWR and deltaEa/deltaWR) were measured. SAC was significantly higher in young subjects compared with elderly subjects, and was significantly related to VO2VT in elderly subjects. SAC also significantly correlated with deltaVO2/deltaWR, deltaCO/deltaWR and deltaEa/deltaWR in elderly subjects. When total subjects were divided by the value of SAC into 6 groups, the VO2VT values in the 3 groups with lower SAC were significantly lower than those in the 3 groups with higher SAC, and gradually decreased with the reduction of SAC. There were no changes in VO2VT among the 3 groups with higher SAC. These results suggest that the participation of SAC in aerobic capacity is significant even during sub-maximal exercise in individuals who show a pronounced age-related reduction of SAC.

Reduction of systemic arterial compliance (SAC) with aging increases left ventricular afterload. The present study was designed to examine whether age-related reduction of SAC is related to excessive myocardial oxygen consumption during sub-maximal aerobic exercise. We studied elderly (60-69 years; n = 25) and senior (70-82 years; n = 25) subjects. We measured SAC immediately before the start of the ramp-fashion exercise (i.e., at the end of the 20 W warm-up exercise) and the double product (DP: systolic blood pressure x heart rate) during the ramp-fashion exercise (20-50 W). SAC was significantly lower in senior subjects (0.76 +/- 0.25 ml mmHg(-1) m(-2)) compared with elderly subjects (0.95 +/- 0.22 ml mmHg(-1) m(-2)). DP was higher in senior subjects (20 W: 14.3 +/- 3.1; 30 W: 15.9 +/- 4.2; 40 W: 17.7 +/- 4.9; 50 W: 20.6 +/- 5.6 [x 10(3) mmHg bpm]) than in elderly subjects (12.8 +/- 3.0, 14.0 +/- 3.5, 15.1 +/- 4.0, 17.1 +/- 4.3 [x 10(3) mmHg bpm]). In total subjects, SAC correlated significantly with DP (r = -0.64, r = -0.64, r = -0.64, r = -0.64). In senior subjects, SAC was related significantly to DP (r = -0.83, r = -0.78, r = -0.76, r = -0.74). In elderly subjects, SAC tended to correlate with DP although its relationships were not statistically significant (r = -0.34, r = -0.36, r = -0.33, r = -0.31). Correlation coefficients at each respective exercise intensity were significantly higher in senior subjects compared with elderly subjects. These results suggest that the age-related reduction of SAC is related to excessive myocardial oxygen consumption during sub-maximal aerobic exercise in older humans, but this relation does not become significant until the SAC reduction becomes pronounced.

A reduction in central arterial compliance has been identified as an independent risk factor for future cardiovascular disease. The aim of the present study was to determine the influence of age-related carotid arterial enlargement on carotid arterial compliance in postmenopausal females, using a cross-sectional study design. Carotid arterial properties were measured with applanation tonometry and ultrasound system in 113 normotensive females (aged 50-78). Brachial-ankle pulse wave velocity (baPWV) measured by a plethysmographic technique was used as an index of arterial stiffness. In comparisons among the three age groups (50-59, 60-69, and 70-78 years old), baPWV (F=11.9, p<0.001) and carotid systolic (F=4.5, p<0.05) and pulse pressures (F=9.6, p<0.0001), and lumen diameter (F=5.6, p<0.01) increased with advancing age. Carotid arterial compliance gradually decreased with age, but not significantly. A stepwise regression analysis revealed that carotid systolic pressure and lumen diameter and age were independent correlates of carotid arterial compliance. After carotid lumen diameter was taken into account (ANCOVA), the differences in carotid arterial compliance among the three age groups became significant (F=3.8, p<0.05). These results suggest that an increase in arterial lumen diameter might compensate for the age-related increase in arterial stiffness and limit the deterioration of the buffering capacity of the central artery in normotensive postmenopausal females.

Endothelial function deteriorates with aging. On the other hand, exercise training improves the function of vascular endothelial cells. Endothelin-1 (ET-1), which is produced by vascular endothelial cells, has potent constrictor and proliferative activity in vascular smooth muscle cells and, therefore, has been implicated in regulation of vascular tonus and progression of atherosclerosis. We previously reported significantly higher plasma ET-1 concentration in middle-aged than in young humans, and recently we showed that plasma ET-1 concentration was significantly decreased by aerobic exercise training in healthy young humans. We hypothesized that plasma ET-1 concentration increases with age, even in healthy adults, and that lifestyle modification (i.e., exercise) can reduce plasma ET-1 concentration in previously sedentary older adults. We measured plasma ET-1 concentration in healthy young women (21-28 yr old), healthy middle-aged women (31-47 yr old), and healthy older women (61-69 yr old). The plasma level of ET-1 significantly increased with aging (1.02 +/- 0.08, 1.33 +/- 0.11, and 2.90 +/- 0.20 pg/ml in young, middle-aged, and older women, respectively). Thus plasma ET-1 concentration was markedly higher in healthy older women than in healthy young or middle-aged women (by approximately 3- and 2-fold, respectively). In healthy older women, we also measured plasma ET-1 concentration after 3 mo of aerobic exercise (cycling on a leg ergometer at 80% of ventilatory threshold for 30 min, 5 days/wk). Regular exercise significantly decreased plasma ET-1 concentration in the healthy older women (2.22 +/- 0.16 pg/ml, P < 0.01) and also significantly reduced their blood pressure. The present study suggests that regular aerobic-endurance exercise reduces plasma ET-1 concentration in older humans, and this reduction in plasma ET-1 concentration may have beneficial effects on the cardiovascular system (i.e., prevention of progression of hypertension and/or atherosclerosis by endogenous ET-1).

Appendicular skeletal muscle mass decreases with advancing age, and this is thought to be a key factor for reductions in functional independence in the elderly. We determined the potential modulatory influence of regular aerobic exercise on the age-related reductions in appendicular muscle mass. In the present cross-sectional study, we studied a total of 131 healthy men aged 20-79 years. For at least the previous 2 years subjects were either sedentary or endurance-trained. Appendicular skeletal muscle mass was measured using dual-energy X-ray absorptiometry. There were no significant group differences in height. Body mass and body surface area were lower in endurance-trained compared with sedentary men (P<0.05). In general, body fat increased with age in both groups, but was lower in endurance-trained compared with sedentary men at any age group (P<0.05). Lean body mass and maximal oxygen consumption decreased with age (P<0.05). Irrespective of expression (absolute, relative to body surface area, or relative to body mass), arm, leg, and total limb muscle mass generally decreased with age. Absolute appendicular muscle mass was not different between the two activity groups. When expressed relative to body mass or body surface area, appendicular muscle mass in the endurance-trained middle-aged and older men was significantly higher than their sedentary peers. The rate of decline in appendicular muscle mass with age was similar between the two activity groups. The results of the present cross-sectional study indicate that endurance-trained men had significantly higher appendicular skeletal muscle mass relative to body mass or body size compared with their sedentary peers. This may contribute, at least in part, to the lower incidence of functional disability observed in middle-aged and older men who exercise regularly.

Using positron emission tomography (PET), cerebral blood flow (CBF) and cerebral metabolic rate of oxygen (CMRO2) were measured in 32 healthy volunteers aged from 27 to 67 years. In bilateral putamen, left supratemporal, left infrafrontal and left parietal cortices, CMRO2 showed a significant decline during aging. The age-related decline of CBF was seen only at the left superior temporal cortex. The mean CMRO2 was significantly lower in the elder group (over 51 years old) than in the younger group (under 50 years old), whereas no significant difference in mean CBF between the two groups. The poor correlation of CBF to the age could be explained partly by the fact that CBF is easily influenced by the physiological, psychological and/or environmental factors. The age-related changes of CMRO2 were more marked in the association cortices of the left hemisphere than in that of the right hemisphere.

This paper is an analysis of normal craniofacial growth in adolescent crab-eating macaques (Macaca fascicularis). Eight female adolescent monkeys were used in this study. Their individual craniofacial growth was studied for a 24-month period utilizing tantalum implants and roentgenographic cephalograms. Throughout the observation period, each monkey consistently showed a class I molar relationship with a good overjet and overbite. The amount of anterior displacement of the maxilla and the mandible was significantly dominant compared to the vertical displacements at every observation period. The midface exhibited a maxillary differential growth pattern in which the premaxilla displaced superiorly and the posterior maxilla moved inferiorly, resulting in a counterclockwise rotation of the entire maxilla. Growth of the lower anterior teeth and alveolar bone compensated for the incremental vertical spaces which were induced by superior displacement of the premaxilla and inferior repositioning of the chin. In addition, the amount of anterior displacement of the upper and lower anterior teeth were significantly larger than that of the premaxilla and the chin. The dentocraniofacial growth pattern in Macaca fascicularis was quite similar to that seen in Macaca mulatta.

We previously demonstrated that the Modelflow method provides a reliable estimation of cardiac output during submaximal exercise in young people, but did not address this issue in elderly people. The present study tested the reliability of the Modelflow method for cardiac output estimation during submaximal exercise in elderly people. Four elderly subjects performed a multi-step stage cycle ergometer exercise at intensities corresponding to the 70, 90, 110 and 130% of their individual ventilatory threshold (VT), and their cardiac output was measured output using Modelflow and Doppler echocardiography methods simultaneously. The correlation coefficient in the overall data obtained by both methods was significant (r = 0.809. P < 0.0001), but the agreement between the two estimates was low not satisfactory (mean error: -1.5 ± 2.6 L · min-1; 95% confidence interval of the bias:-5.0 ∼ 1.9 L · min-1). However, at least below the VT level, the correlation coefficient was becoming higher (r = 0.889, P < 0.0001) and the agreement between the two estimates was much improved (mean error: -0.1 ± 1.2 L · min-1; 95% confidence interval of the bias: -2.6 ∼ 2.3 L · min-1). These results suggest that the Modelflow method provides reliable estimation of cardiac output in elderly people at intensities below the VT. [ABSTRACT FROM AUTHOR]