scholarly journals Age-related Aortic Stiffness Can Be Transferred and Ameliorated via Fecal Microbiota Transplant in Mice

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. 829-830
Author(s):  
Nathan Greenberg ◽  
Nicholas VanDongen ◽  
Rachel Gioscia-Ryan ◽  
Abigail Casso ◽  
David Hutton ◽  
...  
Keyword(s):  
Aortic Stiffness ◽  
Structural Changes ◽  
Fecal Microbiota ◽  
Structural Proteins ◽  
Mechanical Stiffness ◽  
Fecal Microbiota Transplant ◽  
Age Related ◽  
Aortic Stiffening ◽  
Young Mice

Abstract Age-related increases in aortic stiffness contribute to the development of cardiovascular diseases (CVD). To determine whether the gut microbiome (GM) modulates age-related aortic stiffening, we performed fecal microbiota transplants (FMT) between young (Y; 3 month) and older (O; 25 month) male C57BL/6N mice. Following antibiotic treatment (to suppress endogenous microbiota), mice received weekly FMT (fecal samples collected at baseline) via oral gavage for 8-16 weeks from their own (i.e., sham condition: Y-y, O-o [RECIPIENT-donor]) or opposite age group (Y-o, O-y) (N=8-12/group). In vivo aortic stiffness (pulse wave velocity [PWV]) was higher in older vs. young mice at baseline (382±8 vs. 328±7cm/sec, mean±SE, P<0.001). Arterial phenotypes were transferred such that old microbiota transplanted into young mice increased, while young into old decreased, PWV (Y-y: 325±10 vs. Y-o: 362±10cm/sec, P=0.022; O-o: 409±10 vs. O-y: 335±6cm/sec, P<0.001). Intrinsic mechanical stiffness of excised aortic rings (elastic modulus) increased after transplant of old into young (Y-y: 2141±223 vs. Y-o: 3218±394kPA, P=0.022), and decreased with young into old (O-O: 3263±217 vs. O-y: 2602±136kPA, P=0.016), indicating the GM mediates aortic stiffening by modulating structural changes in the arterial wall. Age-related increases in aortic abundance of advanced glycation end products (AGEs), which cross-link arterial structural proteins, tended to be transferred by the GM (Y-y: 0.022±0.001 vs. Y-o: 0.038±0.006 A.U., P=0.11; O-o: 0.120±0.029 vs. O-y: 0.038±0.009 A.U., P=0.06). The aging GM can induce aortic stiffening via promoting AGEs accumulation and crosslinking of arterial structural proteins, and thus might be a promising target for preventing/treating age-related aortic stiffening and CVD.

scholarly journals Electromechanical and structural alterations in the aging rabbit heart and aorta

2012 ◽  
Vol 302 (8) ◽  
pp. H1625-H1635 ◽  
Author(s):  
Leroy L. Cooper ◽  
Katja E. Odening ◽  
Min-Sig Hwang ◽  
Leonard Chaves ◽  
Lorraine Schofield ◽  
...  
Keyword(s):  
Conduction Velocity ◽  
Structural Changes ◽  
Optical Mapping ◽  
Diastolic Pressure ◽  
Ex Vivo ◽  
Rabbit Model ◽  
Systolic Pressure ◽  
Age Related ◽  
Sheet Structure

Aging increases the risk for arrhythmias and sudden cardiac death (SCD). We aimed at elucidating aging-related electrical, functional, and structural changes in the heart and vasculature that account for this heightened arrhythmogenic risk. Young (5–9 mo) and old (3.5–6 yr) female New Zealand White (NZW) rabbits were subjected to in vivo hemodynamic, electrophysiological, and echocardiographic studies as well as ex vivo optical mapping, high-field magnetic resonance imaging (MRI), and histochemical experiments. Aging increased aortic stiffness (baseline pulse wave velocity: young, 3.54 ± 0.36 vs. old, 4.35 ± 0.28 m/s, P < 0.002) and diastolic (end diastolic pressure-volume relations: 3.28 ± 0.5 vs. 4.95 ± 1.5 mmHg/ml, P < 0.05) and systolic (end systolic pressure-volume relations: 20.56 ± 4.2 vs. 33.14 ± 8.4 mmHg/ml, P < 0.01) myocardial elastances in old rabbits. Electrophysiological and optical mapping studies revealed age-related slowing of ventricular and His-Purkinje conduction (His-to-ventricle interval: 23 ± 2.5 vs. 31.9 ± 2.9 ms, P < 0.0001), altered conduction anisotropy, and a greater inducibility of ventricular fibrillation (VF, 3/12 vs. 7/9, P < 0.05) in old rabbits. Histochemical studies confirmed an aging-related increased fibrosis in the ventricles. MRI showed a deterioration of the free-running Purkinje fiber network in ventricular and septal walls in old hearts as well as aging-related alterations of the myofibrillar orientation and myocardial sheet structure that may account for this slowed conduction velocity. Aging leads to parallel stiffening of the aorta and the heart, including an increase in systolic stiffness and contractility and diastolic stiffness. Increasingly, anisotropic conduction velocity due to fibrosis and altered myofibrillar orientation and myocardial sheet structure may contribute to the pathogenesis of VF in old hearts. The aging rabbit model represents a useful tool for elucidating age-related changes that predispose the aging heart to arrhythmias and SCD.

scholarly journals Loss of D2 Receptor Binding with Age in Rhesus Monkeys: Importance of Correction for Differences in Striatal Size

1999 ◽  
Vol 19 (2) ◽  
pp. 218-229 ◽  
Author(s):  
Evan D. Morris ◽  
Svetlana I. Chefer ◽  
Mark A. Lane ◽  
Raymond F. Muzic ◽  
Dean F. Wong ◽  
...  
Keyword(s):  
Receptor Binding ◽  
Rhesus Monkeys ◽  
Structural Changes ◽  
D2 Receptor ◽  
Binding Potential ◽  
Age Related ◽  
Positron Emission ◽  
Dopamine Receptor Binding

The relation between striatal dopamine D2 receptor binding and aging was investigated in rhesus monkeys with PET. Monkeys (n = 18, 39 to 360 months of age) were scanned with 11C-raclopride; binding potential in the striatum was estimated graphically. Because our magnetic resonance imaging analysis revealed a concomitant relation between size of striatum and age, the dynamic positron emission tomography (PET) data were corrected for possible partial volume (PV) artifacts before parameter estimation. The age-related decline in binding potential was 1% per year and was smaller than the apparent effect if the age-related change in size was ignored. This is the first in vivo demonstration of a decline in dopamine receptor binding in nonhuman primates. The rate of decline in binding potential is consistent with in vitro findings in monkeys but smaller than what has been measured previously in humans using PET. Previous PET studies in humans, however, have not corrected for PV error, although a decline in striatal size with age has been demonstrated. The results of this study suggest that PV correction must be applied to PET data to accurately detect small changes in receptor binding that may occur in parallel with structural changes in the brain.

scholarly journals Mitochondria-targeted antioxidant therapy with MitoQ ameliorates aortic stiffening in old mice

2018 ◽  
Vol 124 (5) ◽  
pp. 1194-1202 ◽  
Author(s):  
Rachel A. Gioscia-Ryan ◽  
Micah L. Battson ◽  
Lauren M. Cuevas ◽  
Jason S. Eng ◽  
Michael P. Murphy ◽  
...  
Keyword(s):  
Pulse Wave Velocity ◽  
Wave Velocity ◽  
Aortic Stiffness ◽  
Pulse Wave ◽  
Therapeutic Strategies ◽  
Elastin Degradation ◽  
Age Related ◽  
Clinical Disorders ◽  
Aortic Stiffening ◽  
Old Mice

Aortic stiffening is a major independent risk factor for cardiovascular diseases, cognitive dysfunction, and other chronic disorders of aging. Mitochondria-derived reactive oxygen species are a key source of arterial oxidative stress, which may contribute to arterial stiffening by promoting adverse structural changes—including collagen overabundance and elastin degradation—and enhancing inflammation, but the potential for mitochondria-targeted therapeutic strategies to ameliorate aortic stiffening with primary aging is unknown. We assessed aortic stiffness [pulse-wave velocity (aPWV)], ex vivo aortic intrinsic mechanical properties [elastic modulus (EM) of collagen and elastin regions], and aortic protein expression in young (~6 mo) and old (~27 mo) male C57BL/6 mice consuming normal drinking water (YC and OC) or water containing mitochondria-targeted antioxidant MitoQ (250 µM; YMQ and OMQ) for 4 wk. Both baseline and postintervention aPWV values were higher in OC vs. YC (post: 482 ± 21 vs. 420 ± 5 cm/s, P < 0.05). MitoQ had no effect in young mice but decreased aPWV in old mice (OMQ, 426 ± 20, P < 0.05 vs. OC). MitoQ did not affect age-associated increases in aortic collagen-region EM, collagen expression, or proinflammatory cytokine expression, but partially attenuated age-associated decreases in elastin region EM and elastin expression. Our results demonstrate that MitoQ reverses in vivo aortic stiffness in old mice and suggest that mitochondria-targeted antioxidants may represent a novel, promising therapeutic strategy for decreasing aortic stiffness with primary aging and, possibly, age-related clinical disorders in humans. The destiffening effects of MitoQ treatment may be at least partially mediated by attenuation/reversal of age-related aortic elastin degradation. NEW & NOTEWORTHY We show that 4 wk of treatment with the mitochondria-specific antioxidant MitoQ in mice completely reverses the age-associated elevation in aortic stiffness, assessed as aortic pulse-wave velocity. The destiffening effects of MitoQ treatment may be at least partially mediated by attenuation of age-related aortic elastin degradation. Our results suggest that mitochondria-targeted therapeutic strategies may hold promise for decreasing arterial stiffening with aging in humans, possibly decreasing the risk of many chronic age-related clinical disorders.

scholarly journals Computational evaluation of an extra-aortic elastic-wrap applied to simulated aging anisotropic human aorta models

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Christian Legerer ◽  
Zakaria A. Almsherqi ◽  
Socrates Dokos ◽  
Craig S. McLachlan
Keyword(s):  
Aortic Stiffness ◽  
Structural Changes ◽  
Aortic Wall ◽  
Human Subjects ◽  
Aortic Distensibility ◽  
The Elderly ◽  
Human Aorta ◽  
Element Analysis

AbstractStructural changes occurring to the aortic wall can result in vascular stiffening. This is represented by a loss of vascular compliance during pulsatile flow, resulting in increased systolic and pulse blood pressure, particularly in populations aged 50 and over. Aortic stiffness is thought to be permanent and an active de-stiffening strategy is yet to be developed. Extra aortic elastic wrapping has been proposed as a surgical technique to boost aortic distensibility and treat hypertension in the elderly. Previously, in-vivo and in-vitro testing have suggested a pulse-pressure reduction potential of elastic wrapping in the stiffened aortas. Herein, we explore the feasibility of elastic aortic wrapping to improve simulated aortic compliance across the age span. Detailed computational studies of the anisotropic aortic wall mechanics, using data from human subjects, were performed, evaluating key performance properties for the interaction between the aortic wall and elastic aortic wrap procedure. Main determinants of the procedure’s efficiency are identified using a pre-defined aortic stiffness and wrap elasticity. Finite element analysis predicts that segmental aortic distensibility can be increased if elastic wrapping is applied to a simulated stiff aorta. Elastic aortic wrapping is calculated to have little impact on the compliance of an initially distensible aorta.

scholarly journals Istaroxime treatment ameliorates calcium dysregulation in a zebrafish model for Phospholamban R14del cardiomyopathy

2020 ◽  
Author(s):  
S.M. Kamel ◽  
C.J.M. van Opbergen ◽  
C.D. Koopman ◽  
A.O. Verkerk ◽  
Y. L. Onderwater ◽  
...  
Keyword(s):  
Structural Changes ◽  
Cellular Level ◽  
Zebrafish Model ◽  
Physiological Processes ◽  
Cardiac Contractile ◽  
Age Related ◽  
Intracellular Ca ◽  
Cardiac Contractile Dysfunction ◽  
Novel Drug

AbstractThe heterozygous phospholamban (PLN) p.Arg14del (R14del) mutation is found in patients with dilated or arrhythmogenic cardiomyopathy. The PLN R14del mutation triggers cardiac contractile dysfunction and arrhythmogenesis by affecting intracellular Ca2+ dynamics. Little is known about the physiological processes preceding PLN R14del induced cardiomyopathy, which is characterized by sub-epicardial accumulation of fibrofatty tissue, and a specific drug treatment is currently lacking. Here, we addressed these issues using a knock-in PLN R14del zebrafish model. Hearts from adult zebrafish with the R14del mutation display age-related remodeling with sub-epicardial inflammation and fibrosis. Echocardiography revealed contractile pulsus alternans before overt structural changes occurred, which correlated at the cellular level with action potential duration (APD) alternans. These functional alterations are preceded by diminished Ca2+ transient amplitudes in embryonic hearts. We found that istaroxime treatment ameliorates the in vivo Ca2+ dysregulation, rescues the cellular APD alternans, while it improves cardiac relaxation. Thus, we present novel insight into the pathophysiology of PLN R14del cardiomyopathy and identify istaroxime as a potential novel drug for its treatment.

scholarly journals Demonstration Of Age-Related Increase In Blood-Brain Barrier Permeability By Longitudinal Intravital Microscopy

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. 666-666
Author(s):  
Adam Nyul Toth ◽  
Stefano Tarantini ◽  
Jordan DelFavero ◽  
Feng Yan ◽  
Zoltan Ungvari ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Longitudinal Assessment ◽  
Aged Mice ◽  
Two Photon ◽  
Blood Brain ◽  
Age Related ◽  
Bbb Permeability ◽  
Young Mice

Abstract Age-related blood-brain barrier disruption and cerebromicrovascular rarefaction contribute importantly to the pathogenesis of both vascular cognitive impairment and dementia (VCID) and Alzheimer's disease (AD). Recent advances in geroscience research enable development of novel interventions to reverse age-related alterations of the cerebral microcirculation for prevention of VCID and AD. To facilitate this research there is an urgent need for sensitive and easy-to-adapt imaging methods, which enable longitudinal assessment of changes in BBB permeability and brain capillarization in aged mice, that could be used in vivo to evaluate treatment efficiency. To enable longitudinal assessment of changes in BBB permeability in aged mice equipped with a chronic cranial window, we adapted and optimized two different intravital two-photon imaging approaches. By assessing relative fluorescence changes over the baseline within a volume of brain tissue, after qualitative image subtraction of the brain microvasculature, we confirmed that in 24 month old C57BL/6J mice cumulative permeability of the microvessels to fluorescent tracers of different molecular weights (0.3 kDa to 40 kDa) is significantly increased as compared to that of 5 month old mice. Real-time recording of vessel cross-sections showed that apparent solute permeability of single microvessels is significantly increased in aged mice vs. young mice. Cortical capillary density, assessed both by intravital two-photon microscopy and optical coherence tomography (OCT) was also decreased in aged mice vs. young mice. The presented methods have been optimized for longitudinal (over the period of 36 weeks) in vivo assessment of cerebromicrovascular health in preclinical geroscience research.

scholarly journals Monitoring Age-Related Susceptibility of Young Mice To Oral Salmonella enterica Serovar Typhimurium Infection Using an In Vivo Murine Model

2005 ◽  
Vol 58 (1) ◽  
pp. 153-158 ◽  
Author(s):  
Stacy M Burns-Guydish ◽  
Isoken N Olomu ◽  
Hui Zhao ◽  
Ronald J Wong ◽  
David K Stevenson ◽  
...  
Keyword(s):  
Murine Model ◽  
Salmonella Enterica ◽  
Salmonella Enterica Serovar Typhimurium ◽  
Age Related ◽  
Serovar Typhimurium ◽  
Young Mice

scholarly journals Fecal Microbiota Transplant from Highly Feed-Efficient Donors Shows Little Effect on Age-Related Changes in Feed-Efficiency-Associated Fecal Microbiota from Chickens

2017 ◽  
Vol 84 (2) ◽  
Author(s):  
Sina-Catherine Siegerstetter ◽  
Renée M. Petri ◽  
Elizabeth Magowan ◽  
Peadar G. Lawlor ◽  
Qendrim Zebeli ◽  
...  
Keyword(s):  
Feed Intake ◽  
Feed Efficiency ◽  
Body Weight Gain ◽  
Nutrient Retention ◽  
Fecal Microbiota ◽  
Microbial Colonization ◽  
Microbiota Composition ◽  
Fecal Microbiota Transplant ◽  
Content Type ◽  
Age Related

ABSTRACT Chickens with good or poor feed efficiency (FE) have been shown to differ in their intestinal microbiota composition. This study investigated differences in the fecal bacterial community of highly and poorly feed-efficient chickens at 16 and 29 days posthatch (dph) and evaluated whether a fecal microbiota transplant (FMT) from feed-efficient donors early in life can affect the fecal microbiota in chickens at 16 and 29 dph and chicken FE and nutrient retention at 4 weeks of age. A total of 110 chickens were inoculated with a FMT or a control transplant (CT) on dph 1, 6, and 9 and ranked according to residual feed intake (RFI; the metric for FE) on 30 dph. Fifty-six chickens across both inoculation groups were selected as the extremes in RFI (29 low, 27 high). RFI-related fecal bacterial profiles were discernible at 16 and 29 dph. In particular, Lactobacillus salivarius, Lactobacillus crispatus, and Anaerobacterium operational taxonomic units were associated with low RFI (good FE). Multiple administrations of the FMT only slightly changed the fecal bacterial composition, which was supported by weighted UniFrac analysis, showing similar bacterial communities in the feces of both inoculation groups at 16 and 29 dph. Moreover, the FMT did not change the RFI and nutrient retention of highly and poorly feed-efficient recipients, whereas it tended to increase feed intake and body weight gain in female chickens. This finding suggests that host- and environment-related factors may more strongly affect chicken fecal microbiota and FE than the FMT. IMPORTANCE Modulating the chicken's early microbial colonization using a FMT from highly feed-efficient donor chickens may be a promising tool to establish a more desirable bacterial profile in recipient chickens, thereby improving host FE. Although FE-associated fecal bacterial profiles at 16 and 29 dph could be established, the microbiota composition of a FMT, when administered early in life, may not be a strong factor modulating the fecal microbiota at 2 to 4 weeks of life and reducing the variation in chicken's FE. Nevertheless, the present FMT may have potential benefits for growth performance in female chickens.

scholarly journals In vivo evaluation of posterior eye elasticity using shaker-based optical coherence elastography

2020 ◽  
Vol 245 (4) ◽  
pp. 282-288 ◽  
Author(s):  
Xuejun Qian ◽  
Runze Li ◽  
Yan Li ◽  
Gengxi Lu ◽  
Youmin He ◽  
...  
Keyword(s):  
Shear Wave ◽  
Wave Speed ◽  
Structural Changes ◽  
Biomechanical Properties ◽  
Age Related Macular Degeneration ◽  
Large Field ◽  
Optical Coherence ◽  
Shear Wave Speed ◽  
Age Related

Age-related macular degeneration (AMD) is a progressive retinal disease and becomes the leading cause of blindness. It is well established that early detection is the key to preservation of functional vision. However, it is very difficult to diagnose AMD in very early stages, before structural changes are evident. Consequently, investigating the biomechanical properties of the retina maybe essential for understanding its physiological function. In this study, we present a shear wave-based quantitative method for estimating the elasticity of the posterior eye using shaker-based optical coherence elastography. This technique has been developed and validated on both a homogeneous phantom and a healthy rabbit in vivo. The shear wave speed from the ganglion side to the photoreceptor side of the rabbit eye is 4.1 m/s, 4.9 m/s, and 6.7 m/s, respectively. In addition, the most stiff sclera region has an average shear wave speed of 9.1 m/s. The results demonstrate the feasibility of using this technique to quantify biomechanical properties of the posterior eye and its potential translation to the clinical study. Impact statement Herein, we propose a potentially clinical applicable shaker-based optical coherence elastography (OCE) technique to characterize the biomechanical properties of the posterior eye, including different layers of the retina. Compared with either acoustic radiation force OCE or air-puff OCE, the newly developed method can induce sufficient shear wave propagation at the posterior eye with high resolution and large field of view.

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