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Age-related vascular dysfunction in large elastic and resistance arteries is associated with reductions in microvascular perfusion and elevations in blood pressure. Recent evidence indicates that telomere uncapping-induced senescence in vascular cells may be an important source of oxidative stress and vascular dysfunction in aging, but the causal relationship between these processes has yet to be elucidated. To test this important unexplored hypothesis, we measured arterial senescence signaling and oxidative stress, carotid and mesenteric artery endothelium-dependent vasodilatory capacity, markers of mesenteric microvascular perfusion and endothelial glycocalyx deterioration, and blood pressure in a novel mouse model of Cre-inducible whole body Trf2 deletion and telomere uncapping. Trf2 deletion led to a 320% increase in arterial senescence signaling (P < 0.05). There was a concurrent 29% and 22% reduction in peak endothelium-dependent vasodilation in carotid and mesenteric arteries, respectively, as well as a 63% reduction in mesenteric microvascular endothelial glycocalyx thickness (all P ≤ 0.01). Mesenteric microvascular perfusion was reduced by 8% and systolic blood pressure was increased by 9% following Trf2 deletion (both P < 0.05). Trf2 deletion also led to a pro-oxidative arterial phenotype characterized by increased in NADPH oxidase gene expression; a 210% increase in superoxide levels that was partly dependent on NADPH oxidase activity; and an oxidative stress-mediated reduction in carotid artery vasodilation (all P ≤ 0.05). Collectively, our findings demonstrate that induced Trf2 deletion leads to telomere uncapping, increased senescence signaling, and oxidative-stress mediated functional impairments in the vasculature similar to those seen in human aging.

Aging adipose tissues (ATs) manifest reduced vascularity and increased hypoxia and inflammation that contribute to local and systemic metabolic dysfunction. However, the mechanisms that underlie these age-related changes are incompletely understood. In this study, we sought to examine insulin-stimulated vasodilation and angiogenesis in the arterial vasculature from three major AT depots, perigonadal white (pgWAT), subcutaneous white (scWAT) and brown (BAT) from young and old mice. Here, we demonstrate that in young mice, insulin-stimulated vasodilation is lower in feed arteries from pgWAT compared to scWAT (p 0.05), but no differences were found between feed arteries in other AT depots (p 0.05). Insulin-stimulated vasodilation was lower in old compared to young feed arteries from all three AT depots (p 0.05 for all). In the presence of endothelial nitric oxide synthase inhibitor, L-NAME, insulin-stimulated vasodilation was decreased in young (p 0.05), but was unaffected in old (p 0.05) from all AT depots. We also observed no age-related differences in endothelium-independent dilation, as assessed by sodium nitroprusside (p 0.05). We next investigated angiogenic capacity of the vasculature in these AT depots. In young mice, BAT vasculature demonstrated the highest angiogenic potential, followed by pgWAT and scWAT. We found that aging decreased angiogenic sprout formation in pgWAT and BAT (both p 0.05), but increased angiogenic potential in scWAT (p 0.05), indicating dissimilar impact of aging on angiogenesis in different AT depots. Collectively, these data suggest that aging leads to a consistent impairment in insulin-stimulated vasodilation and reduction in NO bioavailability in all three AT, although aging differentially impacts angiogenic capacity across different AT depots.

BACKGROUND Elevated android body fat increases the risk of developing cardiometabolic diseases. Postprandial hyperglycemia contributes to the proatherogenic metabolic state evident in android adiposity. Due to the insulinotropic effect of milk‐derived proteins, postprandial hyperglycemia has been shown to be reduced with the addition of dairy products. The purpose of this study was to determine whether one serving of nonfat milk added to an oral glucose tolerance test (OGTT ) could attenuate postprandial hyperglycemia in individuals with elevated android adiposity and whether these improvements would be associated with metabolic and/or peripheral hemodynamic effects. METHODS In this placebo‐controlled, randomized, crossover experimental study, 29 overweight/obese adults (26 ± 1 year) consumed an OGTT beverage (75 g glucose) combined with either nonfat milk (227 g) or a placebo control (12 g lactose + 8 g protein + 207 g water) that was matched for both carbohydrate and protein quantities. RESULTS In the whole sample, blood glucose and insulin concentrations increased over time in both trials with no significant differences between trials. Relative increases in peak blood glucose response were significantly related to android body fat (p < 0.05). The subjects in the highest tertiles of android body fat displayed attenuated hyperglycemic responses as well as improvements in flow‐mediated dilation (FMD) after milk intake. CONCLUSIONS A single serving of nonfat milk may attenuate acute hyperglycemia in individuals with elevated android body fat offering a simple and convenient option for managing elevations in blood glucose.

NEW FINDINGS What is the central question of this study? Do systemic sclerosis patients exhibit impaired nitric oxide-mediated vascular function of the lower limb and are these decrements correlated with plasma biomarkers for inflammation and oxidative stress? What is the main finding and its importance? Findings indicate impaired nitric oxide-mediated vascular function, linked to the incidence of digital ulcers and a milieu of inflammation and oxidative stress. However, the absence of significant correlations between individual biomarkers and blood flow responses suggests that the vasculopathy observed in systemic sclerosis may not be solely the result of derangements in the redox balance or inflammatory signalling. ABSTRACT Systemic sclerosis (SSc) is an autoimmune disease characterized by vasculopathy, which may be the consequence of inflammation and oxidative stress that ultimately leads to a reduced nitric oxide (NO) bioavailability. Passive leg movement (PLM) is a novel methodology for assessing lower limb vascular function that is predominantly NO dependent. We combined this vascular assessment with a comprehensive panel of plasma biomarkers to assess the axis of inflammation, oxidative stress and NO in SSc patients (n = 12; 62 ± 11 years of age) compared with healthy control subjects (n = 17; 60 ± 16 years of age). The PLM-induced changes in leg blood flow (LBF; 191 ± 104 versus 327 ± 217 ml min-1 ) and LBF area under the curve (39 ± 104 versus 125 ± 131 ml) were reduced in SSc compared with control subjects. Stratification of patients according to history of digital ulcer (DU) formation revealed a further reduction in LBF area under the curve in DU (-13 ± 83 ml) versus non-DU (91 ± 102 ml) patients. Biomarkers of inflammation (C-reactive protein) and oxidative stress (malondialdehyde and protein carbonyl) were all elevated in SSc (C-reactive protein, 3299 ± 2372 versus 984 ± 565 ng ml-1 ; malondialdehyde, 3.2 ± 1.1 versus 1.1 ± 0.7 μm; and protein carbonyl, 0.15 ± 0.05 versus 0.12 ± 0.03 nmol mg-1 ), and C-reactive protein was further elevated in patients with a history of DU (4551 ± 2752 versus 2047 ± 1019 ng ml-1 ) compared with non-DU, although these were not individually correlated with changes in LBF. These findings of impaired NO-mediated vascular function, linked to DU and a milieu of inflammation and oxidative stress, suggest that redox balance plays an important, but not necessarily deterministic, role in the vascular pathophysiology of SSc.

Background: Repeated exposure to elevated postprandial triglycerides, as seen with typical Western diets, contributes to atherosclerosis and vascular disease. We determined if a single serving of non-fat milk added to a high fat tolerance test could attenuate postprandial hypertriglyceridemia in individuals who consume a high fat diet. Methods: In this placebo-controlled, randomized, crossover experimental study, 30 overweight/obese adults consumed a high-fat tolerance test meal combined with either non-fat milk, carbohydrate control drink, or caloric control drink. Results: Plasma triglycerides increased over time with no significant differences between interventions. Peak plasma triglyceride levels during HFTT were significantly related to dietary fat intake (r = 0.30, p

Objective.The aim of our study was to determine whether an automated capture and analysis system could detect differences in structure and function of sublingual microvessels in patients with systemic sclerosis (SSc) compared to healthy controls.Methods.Intravital microscopy of the sublingual microcirculation was automatically captured and analyzed in 40 patients with SSc and 10 age-matched healthy controls.Results.Total and perfused microvascular density were lower in patients with SSc compared with controls (total microvascular density: 2471 ± 134 µm/mm2 vs 3067 ± 197 µm/mm2, p = 0.020; perfused microvascular density: 1708 ± 92 µm/mm2 vs 2192 ± 144 µm/mm2, p = 0.009). However, the relative percentage of perfused to total microvascular density was similar between SSc and controls (72 ± 2% vs 71 ± 2%, respectively, p = 0.429). Mean red blood cell (RBC) fraction, which indicates the longitudinal tube hematocrit of microvessel segments, was lower in patients with SSc compared with controls (69 ± 1% vs 77 ± 1%, respectively, p < 0.001). Perfused boundary region (PBR), a marker of endothelial glycocalyx barrier properties, was higher in patients with SSc compared with controls (2.1 ± 0.0 µm vs 1.9 ± 0.0 µm, respectively, p = 0.012), suggestive of a dysfunctional glycocalyx. There was an inverse association of PBR with perfused microvascular density (r = −0.40, p = 0.004) and RBC fraction (r = −0.80, p < 0.001).Conclusion.Our results indicate that automated capture and analysis of sublingual microvessel segments produces detailed, objective microvascular structural and functional data that have allowed us to distinguish patients with SSc from controls. These data suggest that microvascular structural and functional abnormalities present in patients with SSc could be at least partly due to a dysfunctional glycocalyx.

Large elastic artery stiffening and endothelial dysfunction, and associated reductions in nitric oxide (NO) bioavailability, are central features of vascular aging. We have recently demonstrated th...

Atherogenic remodeling often occurs at arterial locations with disturbed blood flow (i.e., low or oscillatory) and both aging and western diet (WD) increase the likelihood for pro-atherogenic remodeling. However, it is unknown if old age and/or a WD modify the pro-atherogenic response to disturbed blood flow. We induced disturbed blood flow by partial carotid ligation (PCL) of the left carotid artery in young and old, normal chow (NC) or WD fed male B6D2F1 mice. Three weeks post-PCL, ligated carotid arteries had greater intima media thickness, neointima formation, and macrophage content compared with un-ligated arteries. WD led to greater remodeling and macrophage content in the ligated artery compared with NC mice, but these outcomes were similar between young and old mice. In contrast, nitrotyrosine content, a marker of oxidative stress, did not differ between WD and NC fed mice, but was greater in old compared with young mice in both ligated and un-ligated carotid arteries. In primary vascular smooth muscle cells, aging reduced proliferation, whereas conditioned media from fatty acid treated endothelial cells increased proliferation. Taken together, these findings suggest that the remodeling and pro-inflammatory response to disturbed blood flow is increased by WD, but is not increased by aging.

Swimming exercise is an ideal and excellent form of exercise for patients with osteoarthritis (OA). However, there is no scientific evidence that regular swimming reduces vascular dysfunction and inflammation and elicits similar benefits compared with land-based exercises such as cycling in terms of reducing vascular dysfunction and inflammation in patients with OA. Forty-eight middle-aged and older patients with OA were randomly assigned to swimming or cycling training groups. Cycling training was included as a non-weight-bearing land-based comparison group. After 12 weeks of supervised exercise training, central arterial stiffness, as determined by carotid-femoral pulse wave velocity, and carotid artery stiffness, through simultaneous ultrasound and applanation tonometry, decreased significantly after both swimming and cycling training. Vascular endothelial function, as determined by brachial flow-mediated dilation, increased significantly after swimming but not after cycling training. Both swimming and cycling interventions reduced interleukin-6 levels, whereas no changes were observed in other inflammatory markers. In conclusion, these results indicate that regular swimming exercise can exert similar or even superior effects on vascular function and inflammatory markers compared with land-based cycling exercise in patients with OA who often has an increased risk of developing cardiovascular disease.

Although the associations between chronic levels of arterial stiffness and blood pressure (BP) have been fairly well studied, it is not clear whether and how much arterial stiffness is influenced by acute perturbations in BP. The primary aim of this study was to determine magnitudes of BP dependence of various measures of arterial stiffness during acute BP perturbation maneuvers. Fifty apparently healthy subjects, including 25 young (20–40 yr) and 25 older adults (60–80 yr), were studied. A variety of BP perturbations, including head-up tilt, head-down tilt, mental stress, isometric handgrip exercise, and cold pressor test, were used to encompass BP changes induced by physical, mental, and/or mechanical stimuli. When each index of arterial stiffness was plotted with mean BP, all arterial stiffness indices, including cardio-ankle vascular index or CAVI ( r = 0.50), carotid-femoral pulse wave velocity or cfPWV ( r = 0.51), brachial-ankle pulse wave velocity or baPWV ( r = 0.61), arterial compliance ( r = −0.42), elastic modulus ( r = 0.52), arterial distensibility ( r = −0.32), β-stiffness index ( r = 0.19), and Young's modulus ( r = 0.35) were related to mean BP (all P < 0.01). Changes in CAVI, cfPWV, baPWV, and elastic modulus were significantly associated with changes in mean BP in the pooled conditions, while changes in arterial compliance, arterial distensibility, β-stiffness index, and Young's modulus were not. In conclusion, this study demonstrated that BP changes in response to various forms of pressor stimuli were associated with the corresponding changes in arterial stiffness indices and that the strengths of associations with BP varied widely depending on what arterial stiffness indices were examined.

The endothelial glycocalyx is a gel-like structure that is bound to the luminal surface of the vascular endothelium. At the interface between flowing blood and endothelial cells, the glycocalyx has several functions that are critical for the maintenance of a healthy vasculature, particularly in regard to the vascular endothelium. Within the vasculature, the glycocalyx modulates vascular resistance to maintain blood flow homogeneity in the microcirculation, mechanotransduces fluid shear stress to the endothelium, and buffers endothelial cells from plasma oxidants, cytokines, and circulating immune cells. In advanced age and cardiovascular disease (CVD), the glycocalyx is deteriorated. Moreover, glycocalyx deterioration may precede traditional measurements of age-related vascular dysfunction, such as impaired endothelium-dependent dilation and large artery stiffness, suggesting that a deteriorated glycocalyx could initiate age-related CVD pathology.

OBJECTIVE: Accumulating evidence suggests the vascular endothelium plays a fundamental role in the pathophysiology of obesity by regulating the functional status of white adipose and systemic metabolism. Roundabout guidance 4 (Robo4) is expressed specifically in endothelial cells and increases vascular stability and inhibits angiogenesis. We sought to determine the role of Robo4 in modulating cardio-metabolic function in response to high fat feeding. METHODS: We examined exercise capacity, glucose tolerance, and white adipose tissue artery gene expression, endothelium-dependent dilation and angiogenesis in wild type and Robo4 knockout mice fed normal chow or a high fat diet (HFD). RESULTS: We found Robo4 deletion enhances exercise capacity in normal chow fed mice and HFD markedly increased the expression of Robo4 ligand Slit2 in white adipose tissue. Deletion of Robo4 increased angiogenesis in white adipose tissue and protected against HFD-induced impairments in white adipose artery vasodilation and glucose intolerance. CONCLUSIONS: We demonstrate a novel functional role for Robo4 in endothelial cell function and metabolic homeostasis in white adipose tissue, with Robo4 deletion protecting against endothelial and metabolic dysfunction associated with a HFD. Our findings suggest that Robo4-dependent signaling pathways may be a novel target in anti-obesity therapy.

Advancing age promotes cardiovascular disease (CVD), the leading cause of death in the United States and many developed nations. Two major age-related arterial phenotypes, large elastic artery stiffening and endothelial dysfunction, are independent predictors of future CVD diagnosis and likely are responsible for the development of CVD in older adults. Not limited to traditional CVD, these age-related changes in the vasculature also contribute to other age-related diseases that influence mammalian health span and potential life span. This review explores mechanisms that influence age-related large elastic artery stiffening and endothelial dysfunction at the tissue level via inflammation and oxidative stress and at the cellular level via Klotho and energy-sensing pathways (AMPK [AMP-activated protein kinase], SIRT [sirtuins], and mTOR [mammalian target of rapamycin]). We also discuss how long-term calorie restriction—a health span- and life span-extending intervention—can prevent many of these age-related vascular phenotypes through the prevention of deleterious alterations in these mechanisms. Lastly, we discuss emerging novel mechanisms of vascular aging, including senescence and genomic instability within cells of the vasculature. As the population of older adults steadily expands, elucidating the cellular and molecular mechanisms of vascular dysfunction with age is critical to better direct appropriate and measured strategies that use pharmacological and lifestyle interventions to reduce risk of CVD within this population.

Regular consumption of low- and nonfat dairy products reduces blood pressure (BP) in adults with elevated BP. Currently, it is unknown if conventional full-fat dairy products exert similar hypotensive effects. We hypothesized that adding full-fat dairy products to the normal routine diet would reduce seated office and ambulatory BP (primary outcome) in adults with elevated BP when compared with a no dairy control. Using a randomized controlled crossover design, 60 adults with elevated systolic BP (systolic/diastolic BP: 120-159/

Age-related microvascular dysfunction is well characterized in rodents and humans, but little is known about the properties of the microvascular endothelial glycocalyx in advanced age. We examined the glycocalyx in microvessels of young and old male C57BL6 mice (young: 6.1 ± 0.1 mo vs. old: 24.6 ± 0.2 mo) using intravital microscopy and transmission electron microscopy and in human participants (young: 29 ± 1 yr vs. old: 60 ± 2 yr) using intravital microscopy. Glycocalyx thickness in mesenteric and skeletal muscle microvessels was 51–54% lower in old compared with young mice. We also observed 33% lower glycocalyx thickness in the sublingual microcirculation of humans in advanced age. The perfused boundary region, a marker of glycocalyx barrier function, was also obtained using an automated capture and analysis system. In advanced age, we observed a 10–22% greater perfused boundary region in mice and humans, indicating a more penetrable glycocalyx. Finally, using this automated analysis system, we examined perfused microvascular density and red blood cell (RBC) fraction. Perfused microvascular density is a marker of microvascular function that reflects the length of perfused microvessel segments in a given area; RBC fraction represents the heterogeneity in RBC presence between microvessel segments. Compared with young, the perfused microvascular density was 16–21% lower and RBC fraction was 5–14% lower in older mice and in older humans. These data provide novel evidence that, across mammalian species, a diminished glycocalyx is present in advanced age and is accompanied by markers of impaired microvascular perfusion. Age-related glycocalyx deterioration may be an important contributor to microvascular dysfunction in older adults and subsequent pathophysiology. NEW & NOTEWORTHY Advanced age is characterized by microvascular dysfunction that contributes to age-related cardiovascular diseases, but little is known about endothelial glycocalyx properties in advanced age. This study reveals, for the first time, lower glycocalyx thickness and barrier function that is accompanied by impaired microvascular perfusion in both mice and humans in advanced age.

Hispanics are at increased risk of acquiring cardiovascular risk factors that contribute to cognitive dysfunction. To compare indices of vascular health to measures of cerebral gray matter integrity, 60 middle-aged Hispanic and non-Hispanic Caucasian participants were matched across age, gender, years of education, and mental status. Arterial stiffness was characterized via β-stiffness index and carotid-femoral pulse-wave velocity, and magnetic resonance imaging estimated cortical thickness in a priori regions of interest known to be susceptible to vascular risk factors. Measures of arterial stiffness were significantly higher in Hispanics than in non-Hispanic Caucasians. Hispanics exhibited thinner left inferior frontal gyrus (LIFG) cortical thickness (p=0.04) with concurrently lower language (p=0.02), memory (p=0.03), and attention-executive functioning (p=0.02). These results suggest that compromised vascular health may occur simultaneously with cortical thinning of the LIFG as an early neuropathological alteration in Hispanics.

Purpose: Ischemic preconditioning (IPC) has been used to protect myocardial cells against ischemia- reperfusion injury and is recently utilized for improving exercise performance. It is unknown whether remote IPC (RIPC) to tissues not involved in exercise can induce similar exercise improvements and what "dose" of IPC is necessary to induce exercise performance benefits. This study determined if unilateral and bilateral upper limb RIPC improves lower body anaerobic power output. Methods: Using two randomized, sham-controlled, crossover study designs, we studied 43 recreationally-active adults. For study 1, unilateral RIPC was used, while for study 2, the ischemic stimuli was increased to bilateral occlusion. After either the RIPC or sham control treatment, subjects completed four 30 s Wingate anaerobic tests on a Monark cycle ergometer with 2 min passive rest between trials. Results: In the unilateral occlusion trial, peak power, mean power, and fatigue index were not different between the two conditions at every Wingate test. In the bilateral occlusion trial, mean power was greater in the RIPC condition during the first Wingate test compared with the sham control (both p

In the present review, we describe the dysfunction in arteries that occurs with advanced aging and review how increased dairy product consumption ameliorates age-related arterial dysfunction and lowers the risk of cardiovascular disease (CVD) as well as type 2 diabetes. High consumption of low- and nonfat dairy products is inversely related to key markers of arterial dysfunction, including elevated blood pressure, arterial stiffening, and endothelial dysfunction. Importantly, adoption of a diet that is high in low- and nonfat dairy products is able to lower blood pressure and reduce arterial stiffness and ameliorate endothelial dysfunction in humans. More importantly, simply adding nonfat dairy products to the normal routine diet results in the amelioration of age-related arterial dysfunction. Consumption of a diet that is high in dairy products is also inversely related to risk of type 2 diabetes, which itself is a major risk factor for the development of CVD. Indeed, there is a substantial overlap of risk factors between type 2 diabetes and CVD, most of which are affected by age-related arterial dysfunction. These risk factors also appear to be ameliorated by high consumption of low- and nonfat dairy products. Nevertheless, the information pertaining to the relation between dairy intake and arterial dysfunction is currently limited, and it is clear that more research is warranted.

Dietary supplementation with pomegranate juice improves isometric strength recovery after unaccustomed eccentric exercise. The purpose of this study was to determine if there is a dose response effect of pomegranate juice supplementation after eccentric exercise isometric strength recovery. Forty-five nonresistance trained, recreationally active men were assigned once-daily pomegranate juice, twice-daily pomegranate juice, or placebo supplementation. On day four of supplementation, 20 min of downhill running and 40 maximal eccentric elbow flexion repetitions were performed. Isometric knee extensor and elbow flexor strength, muscular soreness, and serum myoglobin concentrations were measured prior to exercise and 2, 24, 48, 72, and 96 h after exercise. Throughout the postexercise time period, while isometric knee extensor and elbow flexor strength were similar between once-daily and twice-daily pomegranate juice supplementation groups, isometric strength was significantly higher in pomegranate juice groups than placebo. Knee extensor soreness, elbow flexor soreness, and myoglobin increased in response to exercise but were similar between groups. It is apparent that pomegranate juice supplementation improves strength recovery in leg and arm muscles following eccentric exercise; however, no dose response effect was present. We conclude that once-daily pomegranate juice supplementation is not different from twice-daily supplementation in regards to strength recovery after eccentric exercise.

Arterial vasodilation to increases in wall shear rate is indicative of vascular endothelial function. In humans, the non-invasive measurement of endothelial function can be achieved by employing the flow-mediated dilation technique, typically performed in the brachial or superficial femoral artery. Briefly, a blood pressure cuff placed distal to an ultrasound probe is inflated to a suprasystolic pressure, which results in limb ischemia. After 5 min of occlusion the cuff is deflated, resulting in reactive hyperemia and increases in wall shear rate that signal vasodilatory molecules to be released from the endothelium eliciting vasodilation. Despite the thousands of studies performing flow-mediated dilation in humans, surprisingly, no studies have performed this technique non-invasively in living rats. Considering the recent shift in focus to translational research, the establishment of guidelines for non-invasive measurement of flow-mediated dilation in rats and other rodents would be extremely valuable. In the following article, a protocol is presented for the non-invasive measurement of flow-mediated dilation in brachial and superficial femoral arteries of rats, as those sites are most commonly measured in humans.

Systemic sclerosis (SSc) is a rare autoimmune disease characterized by debilitating fibrosis and vascular dysfunction; however, little is known about the circulatory response to exercise in this population. Therefore, we examined the peripheral hemodynamic and vasodilatory responses to handgrip exercise in 10 patients with SSc (61 ± 4 yr) and 15 age-matched healthy controls (56 ± 5 yr). Brachial artery diameter, blood flow, and mean arterial pressure (MAP) were determined at rest and during progressive static-intermittent handgrip exercise. Patients with SSc and controls were similar in body stature, handgrip strength, and MAP; however, brachial artery blood flow at rest was nearly twofold lower in patients with SSc compared with controls (22 ± 4 vs. 42 ± 5 ml/min, respectively; P < 0.05). Additionally, SSc patients had an ∼18% smaller brachial artery lumen diameter with an ∼28% thicker arterial wall at rest ( P < 0.05). Although, during handgrip exercise, there were no differences in MAP between the groups, exercise-induced hyperemia and therefore vascular conductance were ∼35% lower at all exercise workloads in patients with SSc ( P < 0.05). Brachial artery vasodilation, as assessed by the relationship between Δbrachial artery diameter and Δshear rate, was significantly attenuated in the patients with SSc ( P < 0.05). Finally, vascular dysfunction in the patients with SSc was accompanied by elevated blood markers of oxidative stress and attenuated endogenous antioxidant activity ( P < 0.05). Together, these findings reveal attenuated exercise-induced brachial artery blood flow and conduit arterial vasodilatory dysfunction during handgrip exercise in SSc and suggest that elevated oxidative stress may play a role.

Objective.Arthritis and its associated joint pain act as significant barriers for adults attempting to perform land-based physical activity. Swimming can be an ideal form of exercise for patients with arthritis. Yet there is no information on the efficacy of regular swimming exercise involving patients with arthritis. The effect of a swimming exercise intervention on joint pain, stiffness, and physical function was evaluated in patients with osteoarthritis (OA).Methods.Using a randomized study design, 48 sedentary middle-aged and older adults with OA underwent 3 months of either swimming or cycling exercise training. Supervised exercise training was performed for 45 min/day, 3 days/week at 60–70% heart rate reserve for 12 weeks. The Western Ontario and McMaster Universities Arthritis Index was used to measure joint pain, stiffness, and physical limitation.Results.After the exercise interventions, there were significant reductions in joint pain, stiffness, and physical limitation accompanied by increases in quality of life in both groups (all p < 0.05). Functional capacity as assessed by maximal handgrip strength, isokinetic knee extension and flexion power (15–30% increases), and the distance covered in the 6-min walk test increased (all p < 0.05) in both exercise groups. No differences were observed in the magnitude of improvements between swimming and cycling training.Conclusion.Regular swimming exercise reduced joint pain and stiffness associated with OA and improved muscle strength and functional capacity in middle-aged and older adults with OA. Additionally, the benefits of swimming exercise were similar to the more frequently prescribed land-based cycling training. Trial registration: clinicaltrials.govNCT01836380.

It was reported in 1980s that ages at which peak performance was observed had remained remarkably stable in the past century, although absolute levels of athletic performance increased dramatically for the same time span. The emergence of older (masters) athletes in the past few decades has changed the demographics and age-spectrum of Olympic athletes. The primary aim of the present study was to determine whether the ages at which peak performance was observed had increased in the recent decades. The data spanning 114 years from the first Olympics (1898) to the most recent Olympics (2014) were collected using the publically available data. In the present study, ages at which Olympic medals (gold, silver, and bronze) were won were used as the indicators of peak performance age. Track and field, swimming, rowing, and ice skating events were analyzed. In men, peak performance age did not change significantly in most of the sporting events (except in 100 m sprint running). In contrast, peak performance ages in women have increased significantly since 1980s and consistently in all the athletic events examined. Interestingly, as women's peak performance age increased, they became similar to men's peak ages in many events. In the last 20-30 years, ages at which peak athletic performance is observed have increased in women but not in men.

Blood pressure (BP) reactivity has been assessed by a variety of stimuli, including physical, psychological, and physiological perturbations, that can be further classified into cardiac or vascular...

BACKGROUND The number of new world records has decreased substantially in most athletic events in recent years. There has been enormous growth in participation at Masters events, and older athletes have been competing at the highest levels with much younger athletes. However, the progression of athletic performance over time has not been well investigated in Masters athletes. OBJECTIVE AND METHODS To determine whether older Masters athletes improved athletic performance over time, running and swimming times from 1975 to 2013 were collected biennially. The running event of 100 m was chosen specifically, as it is one of the most popular track and field events that would have attracted a large number of competitors. The middle distance of 400 m as well as 100 m freestyle swimming were also examined to determine whether the results in 100 m sprint event can be confirmed in other events. RESULTS The improvements in fastest 100 m running times over time were not significant. However, all the Masters age-group records improved significantly over time. The slopes of improvements over the years were progressively greater at older age groups with the greatest progression observed at oldest age groups of 75-79 years examined. The general trends were similar for 400 m middle-distance running and 100 m freestyle swimming. CONCLUSIONS While younger athletes' performance has stagnated, Masters athletes improved their athletic performance significantly and progressively over the years. The magnitude of improvements was greater in older age groups gradually closing the gap in athletic performance between younger and older participants.

High consumption of low- and non-fat dairy products is associated with reduced risk of high blood pressure (BP) and central arterial stiffness. However, interventional studies to determine if the addition of non-fat dairy products to the diet is capable of reducing central BP and improving vascular function are lacking. The aim of this study was to determine if the solitary addition of non-fat dairy products to the normal routine diet would reduce central BP and improve vascular function in middle-aged and older adults with elevated BP.Using a randomized, crossover intervention study design, forty-nine adults (44% men, 53 ± 2 years, 170 ± 2 cm, 88 ± 3 kg; mean ± SEM) with elevated BP (134 ± 1/81 ± 1 mm Hg) underwent a High Dairy condition (+4 servings/day of conventional non-fat dairy products) and No Dairy condition (+4 servings/day fruit products) in which all dairy products were removed. Both dietary conditions lasted 4 weeks with a 2-week washout before crossing over into the alternate condition. The High Dairy condition produced reductions in central systolic BP (-3 ± 1 mm Hg) and carotid-femoral pulse wave velocity (-0.5 ± 0.1 m/sec), with a concomitant increase in brachial flow-mediated dilation (+1.1 ± 0.4%) and cardiovagal baroreflex sensitivity (+5 ± 1 ms/mm Hg) (P0.05 for all vs. baseline). In the No Dairy condition, brachial flow-mediated dilation was reduced (-1.0 ± 0.1%, P0.05 vs. baseline).The solitary manipulation of conventional dairy products in the normal routine diet modulates levels of central BP and vascular function in middle-aged and older adults with elevated BP.clinicaltrials.gov Identifier: NCT01577030.

Background: The high consumption of low-fat and nonfat dairy products is associated with reduced risk of high blood pressure. Objective: We aimed to investigate whether the solitary addition of nonfat dairy products to the normal routine diet was capable of lowering blood pressure in middle-aged and older adults with elevated blood pressure. Design: With the use of a randomized, crossover intervention-study design, 49 adults (56% women) with elevated blood pressure (mean 6 SEM age: 53 6 2 y; systolic blood pressure: 135 6 1; diastolic blood pressure: 80 6 1 mm Hg) underwent a high-dairy condition (+4 servings conventional nonfat dairy products/d) and isocaloric no-dairy condition (+4 servings fruit products/d) in which all dairy products were removed. Both dietary conditions lasted 4 wk with a 2-wk washout before crossing over into the alternate condition. Results: The high-dairy condition produced reductions in systolic blood pressure (135 6 1 to 127 6 1 mm Hg) and pulse pressure (54 6 1t o 486 1 mm Hg) (both P , 0.05). The hypotensive effects were observed within 3 wk after the initiation of the dietary intervention and in both casual seated and ambulatory (24-h) measurements (P , 0.05). Pulse pressure was increased after the removal of all dairy products in the no-dairy condition (54 6 1t o 566 1 mm Hg; P , 0.05). There were no changes in diastolic blood pressure after either dietary condition. Conclusion: We concluded that the solitary manipulation of conventional dairy products in the normal routine diet would modulate blood pressure in middle-aged and older adults with prehypertension and hypertension. This trial was registered at clinicaltrials.gov as NCT01577030. Am J Clin Nutr 2014;100:80–7.

Elevated central systolic blood pressure and vascular dysfunction increase the risk of cardiovascular disease. Using a randomized, crossover study design, we tested the hypothesis that the addition...