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 healthspan and potential lifespan. 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, Sirtuins, mTOR). We also discuss how long-term calorie restriction, a healthspan and lifespan 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 utilize pharmacological and lifestyle interventions to prevent against CVD risk within this population.

clinicaltrials.gov NCT01836380.

Acute exercise has been shown to attenuate postprandial plasma triglyceride elevation (PPTG). However, the direct contribution of exercise intensity is less well understood. The purpose of this study was to examine the effects of exercise intensity on PPTG and postprandial fat oxidation. One of three experimental treatments was performed in healthy young men (n = 6): nonexercise control (CON), moderate-intensity exercise (MIE; 50% Vo2peak for 60 min), or isoenergetic high-intensity exercise (HIE; alternating 2 min at 25% and 2 min at 90% Vo2peak). The morning after the exercise, a standardized meal was provided (16 kcal/kg BM, 1.02 g fat/kg, 1.36 g CHO/kg, 0.31 g PRO/kg), and measurements of plasma concentrations of triglyceride (TG), glucose, insulin, and β-hydroxybutyrate were made in the fasted condition and hourly for 6 h postprandial. Indirect calorimetry was used to determine fat oxidation in the fasted condition and 2, 4, and 6 h postprandial. Compared with CON, both MIE and HIE significantly attenuated PPTG [incremental AUC; 75.2 (15.5%), P = 0.033, and 54.9 (13.5%), P = 0.001], with HIE also significantly lower than MIE (P = 0.03). Postprandial fat oxidation was significantly higher in MIE [83.3 (10.6%) of total energy expenditure] and HIE [89.1 (9.8) %total] compared with CON [69.0 (16.1) %total, P = 0.039, and P = 0.018, respectively], with HIE significantly greater than MIE (P = 0.012). We conclude that, despite similar energy expenditure, HIE was more effective than MIE for lowering PPTG and increasing postprandial fat oxidation.

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.

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.

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 viscoelastic and inertial properties of the arterial wall are responsible for the arterial functional role in the cardiovascular system. Cryopreservation is widely used to preserve blood vessels for vascular reconstruction but it is controversially suspected to affect the dynamic behaviour of these allografts. The aim of this work was to assess the cryopreservation's effects on human arteries mechanical properties. Common carotid artery (CCA) segments harvested from donors were divided into two groups: Fresh (n = 18), tested for 24-48 h after harvesting, and Cryopreserved (n = 18) for an average time of 30 days in gas-nitrogen phase, and finally defrosted. Each segment was tested in a circulation mock, and its pressure and diameter were registered at similar pump frequency, pulse and mean pressure levels, including those of normotensive and hypertensive conditions. A compliance transfer function (diameter/pressure) derived from a mathematical adaptive modelling was designed for the on line assessment of the arterial wall dynamics and its frequency response. Assessment of arterial wall dynamics was made by measuring its viscous (eta), inertial (M) and elastic (E) properties, and creep and stress relaxation time constant (tauC and tauSR, respectively). The frequency response characterization allowed to evaluate the arterial wall filter or buffer function. Results showed that non-significant differences exist between wall dynamics and buffer function of fresh and cryopreserved segments of human CCA. In conclusion, our cryopreservation method maintains arterial wall functional properties, close to their fresh values.

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