Koichiro Tanahashi

Aerobic exercise training increases plasma Klotho levels and reduces arterial stiffness in postmenopausal women

The Klotho gene is a suppressor of the aging phenomena, and the secretion as well as the circulation of Klotho proteins decrease with aging. Although habitual exercise has antiaging effects (e.g., a decrease in arterial stiffness), the relationship between Klotho and habitual exercise remains unclear. In the present study, we investigated the effect of habitual exercise on Klotho, with a particular focus on arterial stiffness. First, we examined the correlation between plasma Klotho concentration and arterial stiffness (carotid artery compliance and β-stiffness index) or aerobic exercise capacity [oxygen uptake at ventilatory threshold (VT)] in 69 healthy, postmenopausal women (50-76 years old) by conducting a cross-sectional study. Second, we tested the effects of aerobic exercise training on plasma Klotho concentrations and arterial stiffness. A total of 19 healthy, postmenopausal women (50-76 years old) were divided into two groups: control group and exercise group. The exercise group completed 12 wk of moderate aerobic exercise training. In the cross-sectional study, plasma Klotho concentrations positively correlated with carotid artery compliance and VT and negatively correlated with the β-stiffness index. In the interventional study, aerobic exercise training increased plasma Klotho concentrations and carotid artery compliance and decreased the β-stiffness index. Moreover, the changes in plasma Klotho concentration and arterial stiffness were found to be correlated. These results suggest a possible role for secreted Klotho in the exercise-induced modulation of arterial stiffness.

Aerobic Exercise Training Decreases Plasma Asymmetric Dimethylarginine Concentrations With Increase in Arterial Compliance in Postmenopausal Women

BACKGROUND Asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase, increase with advancing age and menopausal status. ADMA plays a role in endothelial dysfunction and increasing arterial stiffness. Regular aerobic exercise has a positive effect on arterial function (i.e., arterial compliance). This study investigated the effects of aerobic exercise training on plasma ADMA concentrations and arterial compliance in postmenopausal women. METHODS Thirty postmenopausal women were divided into 2 groups: an exercise group (n = 20) and a control group (n = 10). Subjects in the exercise group completed 12 weeks of aerobic exercise training (65%-80% of maximal heart rate, 40-60 min/day, 3-6 days/week). Before and after each intervention, plasma ADMA concentrations and carotid arterial compliance were measured in all participants. RESULTS The baseline plasma ADMA concentrations, carotid arterial compliance, and most other key dependent variables did not differ between the 2 groups. In the exercise group, carotid arterial compliance significantly increased after exercise intervention (P < 0.01), and plasma ADMA concentrations significantly decreased (P < 0.05). In addition, changes in carotid arterial compliance after the exercise intervention were inversely correlated with changes in plasma ADMA concentrations (r = -0.367; P < 0.05). CONCLUSIONS We demonstrated that aerobic exercise training significantly decreased plasma ADMA concentrations with increase in carotid arterial compliance in postmenopausal women. These results suggest that reduction in ADMA may play an important role in the aerobic exercise training-induced increase in arterial compliance.

Taurine Supplementation Reduces Eccentric Exercise-Induced Delayed Onset Muscle Soreness in Young Men

The purpose of the present study was to clarify the effects of taurine supplementation on delayed onset muscle soreness (DOMS) and muscle damage after high-intensity eccentric exercise (ECC) in healthy young men. Twenty-nine healthy young men were recruited and randomly assigned to receive either placebo (n = 14) or taurine supplementation (n = 15) in a double-blind manner. Participants ingested either 2.0 g of placebo or taurine supplement three times a day for 2 weeks before and 3 days after high-intensity ECC. Two weeks after starting supplementation, participants performed two sets of unilateral maximal-effort ECC of the elbow flexors on a Biodex isokinetic dynamometer. Each set consisted of 20 contractions with each contraction lasting 3 s and repeated every 9 s, and a 4 min period of rest in between sets. DOMS (evaluated by the visual analogue scale), upper arm circumference (CIR), elbow range of motion (ROM), and parameters of muscle damage including serum myoglobin (Mb) and creatine kinase (CK) levels, were measured before exercise and for 4 days after ECC. The severity of DOMS 2 days after ECC was significantly less in the taurine group than in the placebo group. The area under the curve for DOMS was also significantly smaller in the taurine group. However, taurine supplementation did not affect muscle damage (CIR, ROM, and serum Mb level and CK activity) after ECC. These results suggest that taurine supplementation effectively decreases DOMS after high-intensity ECC in young healthy men.

Plasma ADMA concentrations associate with aerobic fitness in postmenopausal women.

AIMS Asymmetric dimethylarginine (ADMA) is an endogenous competitive inhibitor of nitric oxide (NO) synthase, an enzyme responsible for the generation of NO. Plasma concentrations of ADMA increase in the elderly and in postmenopausal women. In fact, an elevated ADMA level is a risk factor of cardiovascular disease. Aerobic exercise has a beneficial effect on cardiovascular disease. However, the relationship between ADMA and aerobic fitness is unknown. The aim of this study was to determine whether plasma ADMA concentrations correlate with aerobic fitness levels in postmenopausal women. MAIN METHODS Thirty healthy postmenopausal women aged 50-76 years participated in this study. We measured plasma concentrations of ADMA and oxygen consumption at the ventilatory threshold (VO2VT) as an index of aerobic fitness. Subjects were divided into the low aerobic fitness (Low fitness) and high aerobic fitness (High fitness) groups, and the dividing line was set at the median VO2VT value. KEY FINDINGS VO2VT was significantly higher in the High fitness group than in the Low fitness group (P<0.01). The plasma ADMA concentrations in the High fitness group were significantly lower than those in the Low fitness group (P<0.05). There was a negative correlation between plasma ADMA concentrations and VO2VT (r=-0.532, P<0.01). SIGNIFICANCE We found that plasma ADMA concentrations were associated with aerobic fitness in postmenopausal women. The results of this study suggest that habitual aerobic exercise may decrease plasma ADMA concentrations.

Effect of habitual exercise on urinary liver-type fatty acid-binding protein levels in middle-aged and older adults.

The purpose of this study was to examine the effect of habitual exercise on urinary liver‐type fatty acid‐binding protein (L‐FABP), which can reflect the degree of various stresses on renal proximal tubule related to the progression of renal disease, in middle‐aged and older adults. Cross‐sectional and interventional approaches were used to comprehensively achieve this purpose. In the cross‐sectional study, we investigated the relationship between physical activity levels and urinary L‐FABP levels in 130 middle‐aged and older adults. In the interventional study, subjects (n=31) were divided into two groups: exercise (n=19) and control group (n=12), whereby we examined the effects of 12‐week aerobic exercise training on urinary L‐FABP levels. The cross‐sectional study showed that the urinary L‐FABP levels were significantly lower in the higher physical activity group than in the lower physical activity group (P<.05). In the interventional study, 12‐week aerobic exercise training significantly decreased urinary L‐FABP levels (P<.01). Furthermore, the relative changes in urinary L‐FABP levels were significantly correlated with the relative changes in physical activity levels and mean arterial pressure after intervention (r=−.374 and r=.530, respectively). Our results revealed that the urinary L‐FABP levels were lower in the higher physical activity individuals, and aerobic exercise training decreased urinary L‐FABP levels. These results suggest that habitual exercise appears to be associated with a decrease in the degree of several stresses on renal proximal tubule and to be beneficial for kidney health in middle‐aged and older adults.

Association between muscular strength and intrarenal vascular resistance in middle-aged and older individuals

ABSTRACT A strategy for the preservation of intrarenal vasculature conditions remains obscure in middle‐aged and older individuals without the renal disease. In the present study, we sought to identify whether the maintenance of muscular strength is an effective method of preserving the intrarenal vasculature condition of middle‐aged and older individuals. Therefore, we applied a cross‐sectional approach for investigating the relationship between muscular strength and the condition of the intrarenal vasculature. In 169 middle‐aged and older individuals without renal disease, handgrip strength (HGS) and the renal resistive index (RRI) were measured as the parameters of muscular strength and intrarenal vascular resistance, respectively. The RRI was elevated with aging (rs = 0.499, P < 0.001) and was inversely correlated with HGS (rs = − 0.370, P < 0.001). The relationship between RRI and HGS remained significant after the consideration of confounders, including age and various central hemodynamic parameters. Furthermore, when the individuals were divided into four groups according to age (middle‐aged or older) and the median HGS values, the RRI exhibited the highest values in the older group with lower HGS values (P < 0.001). Our findings indicate that muscular strength as assessed by HGS is independently associated with the RRI (i.e. intrarenal vascular resistance) in middle‐aged and older individuals. This finding suggests that the muscular strength may be one of the key factors to preserve the intrarenal vasculature condition. HighlightsRenal resistive index increases with aging.Handgrip strength is independently associated with the renal resistive index.Muscular strength may be important to preserve intrarenal vasculature condition.

Aerobic exercise training enhances cerebrovascular pulsatility response to acute aerobic exercise in older adults

The brains low resistance ensures a robust blood flow throughout systole and diastole and is susceptible to flow pulsatility. Increased cerebral pulsatility contributes to the progression of cerebrovascular disease. Although aerobic exercise affects vascular function, little is known about the effect of exercise on the cerebral pulsatility index in older adults. The aim of this study was to investigate the effect of exercise training on the post‐exercise cerebral pulsatility response in older adults. Ten healthy older adults participated in a 12‐week exercise training intervention. Before and after the intervention, we measured the pulsatility index of the middle cerebral artery by means of transcranial Doppler method at baseline and following a cycling exercise bout performed at an intensity corresponding to the ventilatory threshold. Before exercise training, there was no significant change in the cerebral pulsatility response to an acute bout of cycling exercise. However, after the intervention, cerebral pulsatility decreased significantly following 30 min of an acute cycling exercise (P < 0.05). This study demonstrated that cerebral pulsatility index did not change following an acute bout of cycling exercise at an intensity corresponding to ventilatory threshold, but that, after 12 weeks of exercise training, cerebral pulsatility index was reduced at 30 min after a single bout of cycling exercise. These results suggest that long‐term aerobic exercise training may enhance the post‐exercise reduction in pulsatility index in older adults.

Lactotripeptide ingestion increases cerebral blood flow velocity in middle-aged and older adults

The age-related decrease in cerebral blood flow velocity increases the risk of cerebrovascular disease. Milk protein-derived bioactive peptides, e.g., lactotripeptide (LTP), have been shown to inhibit angiotensin converting enzyme activities and increase vasodilator production. We hypothesized that LTP ingestion increases cerebral blood flow velocity in middle-aged and older adults. In a randomized, placebo-controlled, double-blind design, 15 healthy middle-aged and older adults were assigned to either a LTP group or a placebo group. The subjects ingested LTP or placebo orally for 8 weeks. Before and after intervention, middle cerebral blood flow velocity was measured using transcranial Doppler ultrasonography. The baseline middle cerebral blood flow velocity and most other key dependent variables did not differ between the groups. LTP ingestion significantly increased middle cerebral blood flow velocity, but there was no such improvement in the placebo groups. We concluded that 8 weeks of LTP ingestion increased middle cerebral blood flow velocity in middle-aged and older adults.

Habitual exercise decreases plasma xanthine oxidoreductase activity in middle-aged and older women

The aim of present study was to investigate the association between plasma xanthine oxidoreductase activity, which has gained attention as a novel preventive target of cardiovascular disease, and various physiological parameters and was to determine the effects of habitual exercise on plasma xanthine oxidoreductase activity in middle-aged and older women. In the cross-sectional study, we investigated the association between plasma xanthine oxidoreductase activity and various physiological parameters in 94 middle-aged and older women. In the interventional study, subjects (n = 22) were divided into two groups: exercise (n = 12) or the control group (n = 10), whereby we examined the effect of 12-week aerobic exercise training on plasma xanthine oxidoreductase activity in middle-aged and older women. The cross-sectional study demonstrated that plasma xanthine oxidoreductase activity was significantly associated with various physiological parameters, including visceral fat and daily step counts. In the interventional study, the plasma xanthine oxidoreductase activity significantly decreased after the 12-week aerobic exercise training, its changes were inversely associated with the changes in daily step counts. Our results revealed that the plasma xanthine oxidoreductase activity was associated with visceral fat accumulation and lack of exercise, and it was decreased by the aerobic exercise training.

Urinary liver-type fatty acid-binding protein is associated with subendocardial viability ratio in middle- and older-aged adults

ABSTRACT Background: To identify one of the physiological underlying mechanisms of the predictive effects of urinary liver-type fatty acid-binding protein (L-FABP) for the onset of cardiovascular disease (CVD), we investigated the relationship between urinary L-FABP levels and subendocardial viability ratio (SEVR), a marker of myocardial perfusion, in middle- and older-aged adults. Methods: This was a cross-sectional study of 249 middle- and older-aged adults (aged 46–83 years). We measured urinary L-FABP levels and central hemodynamic parameters, including SEVR, calculated by pulse wave analysis using an applanation tonometry. Results: In the participants stratified in accordance with the tertiles of urinary L-FABP levels, SEVR decreased in a stepwise fashion with increasing tertiles (p < 0.001). Furthermore, this association remains significant after the consideration of various confounders. On the contrary, urinary albumin levels were not independently related with SEVR. Conclusion: Our results demonstrated that urinary L-FABP levels were independently associated with the SEVR of the middle- and older-aged adults. This result suggests that the increase in urinary L-FABP levels even within the normal range might be related to the decrease in myocardial perfusion (SEVR).