4 Day in dry immersion reproduces partially the aging effect on the arteries as observed during 6 month spaceflight or confinement

The objectives of this study were to determine whether 4 days of dry immersion (DI) induced similar arterial aging as spaceflight and to test the impact of thigh cuffs. Eighteen subjects underwent DI; nine wore thigh cuffs. Cardiac and arterial targets were assessed by ultrasound. No significant differences were found between the groups. The left ventricle volume, stroke volume (SV), and ejection fraction decreased with DI (p < 0.001). Carotid distensibility reduced (p < 0.05), carotid to femoral arterial tree became stiffer in 33% of the subjects, and femoral artery intima media thickness increased (p < 0.05). A reduction in plasma volume is likely to have caused the observed cardiac changes, whereas the arterial wall changes are probably best explained by hypokinesia and/or environmental stress. These changes are similar but lower in amplitude than those observed in spaceflight and mimic the natural aging effect on earth. The daytime-worn thigh cuffs had no acute or chronic impact on these arterial-focused measurements.

Pace of arterial aging and its association with cardiovascular risk factors

Introduction Chronological age is a well-known risk factor of cardiovascular diseases (CVD). In comparison with chronological age, biological arterial age can determine person's individual pace of aging, while difference between biological and chronological arterial age (delta age) can be rated as accelerated or decelerated artery aging. Purpose The aim of this study was to assess the association of risk factors of CVD with accelerated and decelerated arterial aging in almost healthy people. Methods We investigated systolic blood pressure (SBP), blood chemistry (total cholesterol (TC), low- (LDL) and high-density (HDL) lipoproteins, triglycerides (TG), apolipoprotein B (ApoB), fasting glucose (FG), glycated hemoglobin (HbA1c), serum renin levels) and urinary albumine, carotid ultrasonography (presence of atherosclerotic plaques and carotid intima-media thickness), arterial stiffness (AS) and leucocyte telomere length (LTL) in 143 adults (mean age 50.31±12.98 years, 35% male, 29% have hypertension, 15% - type 2 diabetes mellitus (T2DM)). LTL was measured by real-time polymerase chain reaction. AS was measured by pulse wave velocity and augmentation index with applanation tonometry using SphygmoCor device (AtCor, Australia). Biological artery age was estimated according to the age-predicting models, based on arterial wall parameters (A. Fedintsev et al, 2017). All the subjects were divided into groups of “old” and “young” arteries according to the positive or negative delta age – difference between biological and chronological age. The data were analyzed using multivariate logistic and linear regression analysis. Results The main statistically significant results are shown in the table. Arterial pace of aging is closely associated with chronological age, hypertension and glucose metabolism. There were not found any associations of arterial pace of aging with lipid, renin levels, urinary albumin and LTL. Conclusion Hypertension, carbohydrate metabolism are main therapeutic targets for accelerated arterial aging and CVD prevention. FUNDunding Acknowledgement Type of funding sources: None. Results of regression analysis

Dynamic Crosstalk between Vascular Smooth Muscle Cells and the Aged Extracellular Matrix

Vascular aging is accompanied by the fragmentation of elastic fibers and collagen deposition, leading to reduced distensibility and increased vascular stiffness. A rigid artery facilitates elastin to degradation by MMPs, exposing vascular cells to greater mechanical stress and triggering signaling mechanisms that only exacerbate aging, creating a self-sustaining inflammatory environment that also promotes vascular calcification. In this review, we highlight the role of crosstalk between smooth muscle cells and the vascular extracellular matrix (ECM) and how aging promotes smooth muscle cell phenotypes that ultimately lead to mechanical impairment of aging arteries. Understanding the underlying mechanisms and the role of associated changes in ECM during aging may contribute to new approaches to prevent or delay arterial aging and the onset of cardiovascular diseases.

Predicting arterial age using carotid ultrasound images, pulse wave analysis records, cardiovascular biomarkers and deep learning

Cardiovascular disease --an age-related disease-- is the leading cause of death worldwide. We built an arterial age predictor by training deep learning models to predict age from 233,388 pulse wave analysis records, 8,279 carotid ultrasound images and arterial health biomarkers (e.g blood pressure) collected from 502,000 UKB participants. We predicted age with a R-Squared of 67.1+/-0.6% and a root mean squared error of 4.29+/-0.04 years. Attention maps for carotid ultrasound images suggest that the predictions are driven by vascular features, for the largest part. Accelerated arterial aging is 32.6+/-7.3% GWAS-heritable, and we identified 192 single nucleotide polymorphisms in 109 genes (e.g NPR3, involved in blood volume and pressure) significantly associated with this phenotype. Similarly, we identified biomarkers (e.g electrocardiogram features), clinical phenotypes (e.g chest pain), diseases (e.g hypertension), environmental (e.g smoking) and socioeconomic (e.g income and education) variables associated with accelerated arterial aging. Finally, carotid ultrasound images, pulse wave analysis records and blood pressure biomarkers capture different facets of arterial aging. For example, carotid ultrasound-measured and pulse wave analysis-measured accelerated arterial aging phenotypes are only .164+/-.009 correlated. In conclusion, our predictor suggests potential lifestyle and therapeutic interventions to slow arterial aging, and could be used to assess the efficiency of emerging rejuvenating therapies on the arterial system.

Apigenin restores endothelial function by ameliorating oxidative stress, reverses aortic stiffening, and mitigates vascular inflammation with aging

We assessed the efficacy of oral supplementation with the flavanoid apigenin on arterial function during aging and identified critical mechanisms of action. Young (6 months) and old (27 months) C57BL/6N mice (model of arterial aging) consumed drinking water containing vehicle (0.2% carboxymethylcellulose; 10 young, 7 old) or apigenin (0.5 mg/ml in vehicle; 10 young, 9 old) for 6 weeks. In vehicle-treated animals, isolated carotid artery endothelium-dependent dilation (EDD), bioassay of endothelial function, was impaired in old vs young (70±9 vs 92±1 %, P<0.0001) due to reduced nitric oxide (NO) bioavailability. Old mice had greater arterial reactive oxygen species (ROS) production and oxidative stress (higher nitrotyrosine) associated with greater nicotinamide adenine dinucleotide phosphate oxidase (oxidant enzyme) and lower superoxide dismutase 1 and 2 (antioxidant enzymes); ex vivo administration of TEMPOL (antioxidant) restored EDD to young levels, indicating ROS-mediated suppression of EDD. Old animals also had greater aortic stiffness as indicated by higher aortic pulse wave velocity (PWV, 434±9 vs 346±5 cm/sec, P<0.0001) due to greater intrinsic aortic wall stiffness associated with lower elastin levels and higher collagen, advanced glycation end-products (AGEs) and pro-inflammatory cytokine abundance. In old mice, apigenin restored EDD (96±2%) by increasing NO bioavailability, normalized arterial ROS, oxidative stress and antioxidant expression, and abolished ROS inhibition of EDD. Moreover, apigenin prevented foam cell formation in vitro (initiating step in atherosclerosis) and mitigated age-associated aortic stiffening (PWV 373±5 cm/sec) by normalizing aortic intrinsic wall stiffness, collagen, elastin, AGEs, and inflammation. Thus, apigenin is a promising therapeutic for arterial aging.

Abstract P175: Predicting Healthy Arterial Aging Versus Premature Atherosclerosis In Young Adults: The Bogalusa Heart Study

Introduction: Early differentiation of healthy arterial aging versus premature atherosclerosis is important for optimal atherosclerotic cardiovascular disease (ASCVD) risk stratification and prevention. We sought to identify predictors for the long-term absence of carotid plaque in young adults. Hypothesis: Calcium and phosphate are found in excess in atherosclerotic lesions, therefore we hypothesized that mineral markers may help to explain residual heterogeneity in arterial aging phenotypes beyond traditional ASCVD risk factors. Methods: We included 508 participants from the Bogalusa Heart Study without clinical ASCVD who were free of carotid plaque at baseline (2001-02) and underwent ultrasound at follow-up (2013-16). Modified Poisson regression estimated the persistent absence of carotid plaque over 12.8 years. Results: Participants were on average 36.2 years old at baseline, 64% were women, and 29% were African American. Although a majority (97%) of participants had a 10-year ASCVD risk <7.5%, only 68% remained free of plaque ( Figure ). Beyond younger age (RR=1.20, 95% CI: 1.07-1.36, per 10 years) and a total cholesterol-HDL-cholesterol ratio <3.5 (RR=1.15, 95% CI: 1.01-1.30), normal values of traditional risk factors did not predict long-term absence of plaque. Independent from traditional markers, including glomerular filtration rate, serum calcium-phosphate product (RR=1.08, 95% CI: 1.01-1.14, per 1-SD lower), phosphate (RR=1.15, 95% CI: 1.03-1.29, per 1 mg/dL lower), and dietary sodium <2300 mg/day (RR=1.20, 95% CI: 1.03-1.41) significantly associated with non-development of plaque. Conclusions: Lower calcium-phosphate homeostasis and low sodium intake independently associated with long-term absence of carotid plaque. However, nearly one-third of young adults with a relatively low burden of traditional risk factors developed premature atherosclerosis. These results suggest that dietary and intrinsic minerals are early contributors to the development of arterial aging phenotypes.

Treating Arterial Ageing in Patients with Diabetes: From Mechanisms to Effective Drugs

Diabetes mellitus is a major healthcare problem. It is not only characterized by hyperglycemia and chronic complications, but in longer lasting diabetes and a longer living population, it is also associated with accelerated arterial ageing, which importantly contributes to cardiovascular complications. The accelerated arterial ageing in patients with diabetes should be considered separately from arterial ageing in patients without diabetes. Basic and clinical research have allowed better insight into the mechanisms of arterial ageing. In a simplified mechanistic way, it could be considered that the three tightly connected cornerstone characteristics of arterial ageing in patients with diabetes are: phenotypic presentation as endothelial dysfunction and arterial stiffness, and the underlying basic ageing-facilitating mechanism represented as the impaired expression of genetic longevity pathways. Currently, specific drugs for preventing/treating arterial ageing are not available. Therefore, we aimed to review the capacity of available drugs, particularly antidiabetic drugs, to interfere with the arterial ageing process. In the near future, these characteristics could help to guide therapy in patients with diabetes. Overall, it appears that arterial ageing could become a new target in diabetes. The expanding knowledge regarding the capability of antidiabetic drugs and other available drugs to inhibit/delay arterial aging is therefore essential.