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Background: A mismatch between myocardial oxygen supply and demand is the most common cause of ischemic myocardial injury in older persons. The subendocardial viability ratio (SEVR) can usefully estimate the degree of myocardial perfusion relative to left‐ventricular workload. The aim of the present study was to evaluate the ability of SEVR to predict long‐term mortality in the older population. Additionally, we aimed to identify the SEVR cutoff value best predicting total mortality. Methods: This is a multicenter, longitudinal study involving a large population of individuals older than 80 years living in nursing homes. Patients with cancer, severe dementia, and very low level of autonomy were excluded from the study. Participants were monitored for 10 years. Adverse outcomes were recorded every 3 months from inclusion to the end of the study. SEVR reflects the balance between subendocardial oxygen supply and demand, and was estimated non‐invasively by analyzing the carotid pressure waveform recorded by applanation arterial tonometry. Results: A total of 828 people were enrolled (mean age: 87.7 ± 4.7 years, 78% female). 735 patients died within 10 years and 24 were lost to follow‐up. SEVR was inversely associated with mortality at univariate Cox‐regression model (risk ratio, 0.683 per unit increase in SEVR; 95% confidence interval (CI) [0.502–0.930], p = 0.015) and in a model including age, sex, body mass index, Activity of Daily Living index and Mini‐Mental State Examination score (risk ratio, 0.647; 95% CI [0.472–0.930]). The lowest tertile of SEVR was associated with higher 10‐years total mortality than the middle (p < 0.001) and the highest (p < 0.004) tertile. A SEVR cutoff value of 83% was identified as the best predictor of total mortality. Conclusions: SEVR may be considered as a marker of "cardiovascular frailty." An accurate non‐invasive estimation of SEVR could be a useful and independent parameter to assess survival probability in very old adults. Trial Registration: NCT00901355, registered on ClinicalTrials.gov website. [ABSTRACT FROM AUTHOR]

Short telomere length (TL) is associated with atherosclerotic cardiovascular disease (ACVD) and other age-related diseases. It is unclear whether these associations originate from having inherently short TL or a faster TL attrition before or during disease development. We proposed the blood-and-muscle model to assess TL dynamics throughout life course. Our objective was to measure TL in leukocytes (LTL) and in skeletal muscle (MTL), which served as a proxy of TL at birth. The delta (MTL-LTL) represented life-long telomere attrition. Blood draws and skeletal muscle biopsies were performed on 35 Lebanese individuals undergoing surgery. Following DNA extraction, LTL and MTL were measured by Southern blot. In every individual aged between 30 and 85 years, MTL was longer than LTL. With age, MTL and LTL decreased, but the delta (MTL-LTL) increased by 14 bp/year. We validated the blood-and-muscle model that allowed us to identify TL, TL at birth, and lifelong TL attrition in a cross-sectional study. This model can be used in larger cross-sectional studies to evaluate the association of telomere dynamics with age-related diseases onset and progression. Key words: aging, leukocytes, muscle, telomere, Southern blot. Les telomeres (TL) courts sont associes avec la maladie cardiovasculaire atherosclerotique (MCAS) et a d'autres maladies liees au vieillissement. On ne sait toujours pas si ces associations sont issues du fait que les TL soient courts de maniere inherente ou si les TL subissent une attrition plus rapide avant ou pendant l'evolution de la maladie. Nous avons propose un modele << sang et muscle >> en vue d'evaluer la dynamique des TL tout au long de la vie. Notre objectif etait de mesurer les TL dans les leucocytes (TLL) et dans le muscle squelettique (TLM) pour servir de comparateur avec les TL a la naissance. Le delta (TLM-TLL) representait l'attrition des TL au cours de la vie. Nous avons effectue des prelevements sanguins et des biopsies musculaires chez 35 Libanais subissant une intervention chirurgicale. Apres l'extraction de l'ADN, nous avons mesure les TLL et les TLM a l'aide de la technique de buvardage de Southern. Chez toutes les personnes agees de 30 a 85 ans, les TLM etaient plus longs que les TLL. Avec l'age, la longueur des TLM et des TLL diminuait, mais le delta (TLM-TLL) augmentait de 14 pb/annee. Nous avons valide le modele << sang et muscle >>, qui nous a permis d'etablir la longueur des TL, des TL a la naissance et l'attrition des TL tout au long de la vie dans une etude croisee. Ce modele peut etre utilise dans des etudes croisees plus vastes en vue d'evaluer l'association de la dynamique des TL avec l'apparition et l'evolution de maladies liees au vieillissement. [Traduit par la Redaction] Mots-cles : vieillissement, leucocytes, muscle, telomere, buvardage de Southern., Introduction In replicating somatic cells, telomeres, the nucleoproteic structures at the extremities of chromosomes, go through progressive shortening that eventually induces replicative senescence (Blackburn 2005; van Deursen 2014). During early [...]

Adult Brown Norway (BN) rats exhibit numerous internal elastic lamina (IEL) ruptures in the abdominal aorta (AA) and a lower aortic elastin-to-collagen ratio (E/C) compared with other strains. We studied here AA mechanical properties in BN compared with control strains. AA stiffness (assessed by plotting elastic modulus/wall-stress curves obtained under anesthesia), thoracic aorta elastin and collagen contents, and IEL ruptures in AA were measured in male BN and LOU rats aged 6, 10, and 15 wk. The Long Evans (LE) control strain was compared with BN at more advanced ages (15, 28, and 64 wk). At all ages, aortic E/C was lower in BN than in control strains. At 6 wk, AA stiffness was greater in BN than in LOU. In both strains, AA stiffness decreased between 6 and 10 wk, more so in BN than in LOU, and then increased, reaching similar values at 15 wk. BN AA stiffness was not different from that of LE at 15 and 28 wk, but was significantly lower at 64 wk. The increased stiffness in young BN rat AA may be due to the decreased E/C. IEL rupture onset in the BN around 7-8 wk, which decreases stiffness, as suggested by its pharmacological modulation, abolished such differences by 15 wk. Thereafter, age-related AA stiffness increased less in BN than in LE, likely due to the numerous IEL ruptures. We conclude that, in the BN rat, the lower E/C and the presence of IEL ruptures have opposing effects on arterial stiffness. elastin; collagen; incremental elastic modulus-stress curves; abdominal aorta; internal elastic lamina ruptures doi: 10.1152/ajpheart.00040.2010.

We examined the arterial phenotype of mice lacking [[alpha].sub.1]-integrin ([[alpha].sub.1.sup.-/-]) at baseline and after 4 wk of ANG II or norepinephrine (NE) administration. Arterial mechanical properties were determined in the carotid artery (CA). Integrin expression, MAPK kinases, and focal adhesion kinase (FAK) were assessed in the aorta. No change in arterial pressure was observed in [[alpha].sub.1.sup.-/-] mice. Elastic modulus-wall stress curves were similar in [[alpha].sub.1.sup.-/-] and [[alpha].sub.1.sup.+/+] animals, indicating no change in arterial stiffness. The rupture pressure was lower in [[alpha].sub.1.sup.-/-] mice, demonstrating decreased mechanical strength. Lack of [[alpha].sub.1]-integrin was accompanied by an increase in [[beta].sub.1]-, [[alpha].sub.v]-, and [[alpha].sub.5]-integrins but no change in [[alpha].sub.2]--integrin. ANG II increased medial cross-sectional area of the CA in [[alpha].sub.1.sup.+/+], but not [[alpha].sub.1.sup.-/-], mice, whereas equivalent pressor doses of NE did not produce a significant increase in either group. In [[alpha].sub.1.sup.+/+] mice, ANG II induced [[alpha].sub.1]-integrin expression and smooth muscle cell (SMC) hypertrophy in the CA in association with increased aortic expression of [alpha]-smooth muscle actin and smooth muscle myosin heavy chain and phosphorylation of ERK1/2, p38 MAPK, and FAK. ANG II did not induce SMC hypertrophy or phosphorylation of p38 MAPK and FAK in [[alpha].sub.1.sup.-/-] mice. A functional anti-[[alpha].sub.1]-integrin antibody inhibited in vitro the ANG II-induced phosphorylation of FAK and p38 MAPK. In conclusion, [[alpha].sub.1.sup.-/-] mice exhibit a reduced mechanical strength at baseline and a lack of ANG II-induced SMC hypertrophy. These results emphasize the importance of [[alpha].sub.1][[beta].sub.1]-integrin in p38 MAPK and FAK phosphorylation during vascular hypertrophy in response to ANG II. arterial mechanical properties; vascular hypertrophy; MAPK kinases; integrin expression; smooth muscle cells

In spontaneously hypertensive rats (SHR), carotid and aortic distensibilities measured at operational blood pressure (BP) are reduced. Increased body weight and mean arterial pressure (MAP) are both known to reduce distensibility independently. However, whether, after adjustment to body weight and mean BP, distensibility remains reduced in SHR has never been investigated. Carotid and abdominal aorta distensibilities were measured under anesthesia in SHR at 5, 12, 52, and 78 wk of age, and measurements were compared with age-matched normotensive Wistar rats. Each age group was composed of 9 or 10 animals. We determined distensibility using echo-tracking techniques of high resolution. Compared with Wistar rats, carotid and aortic distensibilities measured at operational MAP are reduced in SHR. This reduction is accentuated with age, particularly for the carotid artery. After adjustment to body weight and MAP, carotid and aortic distensibilities become identical in Wistar and SHR (or even slightly increased in SHR) but continue to be reduced with age, mainly for the carotid artery. In conclusion, in SHR, age and high BP do not have a parallel and similar influence on the reduction of arterial distensibility. Aging constantly reduces arterial distensibility, whereas MAP levels contribute to maintenance of arterial function. spontaneously hypertensive rats; carotid distensibility

Background. Aldosterone accelerates cardiovascular aging by mechanisms that generate reactive oxygen species. Telomere length in white blood cells (WBCs) may be a bioindicator that registers the accruing burden of systemic oxidative stress. The aim of the present study was, therefore, to examine the relationship between plasma aldosterone and telomere length in WBCs. Methods. We studied 75 normotensive and never-treated mildly hypertensive men whose blood was drawn for the measurements of plasma aldosterone concentration and the terminal restriction fragment (TRF) length in WBCs. Results. The slope of the TRF--age relationship in the entire cohort showed a decrease in telomere length of 26 [+ or -] 5 base pairs per year (r = -0.46, p < .001). Age-adjusted TRF length was the longest in the lowest aldosterone quartile (6.74 [+ or -] 0.12 kb) and shortest in the highest aldosterone quartile (6.36 [+ or -] 0.11 kb), with intermediate TRF lengths in the second and third aldosterone quartiles (analysis of variance [ANOVA] trend test, p = .025). In telomeric attrition equivalence, participants in the upper aldosterone quartile were 15 years older than their peers in the lowest quartile. Conclusions. The inverse relationship between aldosterone and WBC telomere length suggests not only that aldosterone is pro-oxidant but that elevated concentrations of this hormone might be linked to a higher rate of telomere attrition and perhaps increased biological aging in humans.