Oral Intake of EPA:DHA 6:1 by Middle-Aged Rats for One Week Improves Age-Related Endothelial Dysfunction in Both the Femoral Artery and Vein: Role of Cyclooxygenases

In humans, aging is associated with endothelial dysfunction and an increased risk of venous thromboembolism. Although intake of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) at a ratio of 6:1 by old rats improved the endothelial dysfunction in arteries, the impact on veins remains unclear. Eight-month-old male Wistar rats were either untreated or orally administered corn oil, EPA:DHA 1:1, or EPA:DHA 6:1 (500 mg/kg/d) for seven days. Vascular reactivity was studied by myography. In middle-aged femoral artery rings, acetylcholine caused a partial relaxation at low concentrations and a contractile response at high concentrations, whereas in the old femoral vein only a partial relaxation was observed. The EPA:DHA 6:1 treatment blunted the contractile response to acetylcholine in the middle-aged femoral artery and both EPA:DHA 6:1 and 1:1 increased the relaxation to acetylcholine in the old femoral vein. No such effects were observed with corn oil. Both the non-selective cyclooxygenase inhibitor indomethacin and the COX-1 inhibitor SC-560 increased the relaxation to acetylcholine in the middle-aged femoral artery whereas the COX-2 inhibitor NS-398 increased that in the middle-aged femoral vein. In conclusion, our results indicate that aging is associated with an endothelial dysfunction in the femoral artery and vein, which can be improved by EPA:DHA 6:1 treatment—most likely via a cyclooxygenase-dependent mechanism.

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The Role of Vascular Aging in Atherosclerotic Plaque Development and Vulnerability

Current Pharmaceutical Design ◽

10.2174/1381612825666190830175424 ◽

2019 ◽

Vol 25 (29) ◽

pp. 3098-3111 ◽

Cited By ~ 6

Author(s):

Luca Liberale ◽

Giovanni G. Camici

Keyword(s):

Atherosclerotic Plaque ◽

Molecular Mechanisms ◽

Driving Forces ◽

Plaque Burden ◽

Vascular Aging ◽

Age Related ◽

Plaque Development ◽

Increased Risk ◽

The Impact ◽

Over Time

Background: The ongoing demographical shift is leading to an unprecedented aging of the population. As a consequence, the prevalence of age-related diseases, such as atherosclerosis and its thrombotic complications is set to increase in the near future. Endothelial dysfunction and vascular stiffening characterize arterial aging and set the stage for the development of cardiovascular diseases. Atherosclerotic plaques evolve over time, the extent to which these changes might affect their stability and predispose to sudden complications remains to be determined. Recent advances in imaging technology will allow for longitudinal prospective studies following the progression of plaque burden aimed at better characterizing changes over time associated with plaque stability or rupture. Oxidative stress and inflammation, firmly established driving forces of age-related CV dysfunction, also play an important role in atherosclerotic plaque destabilization and rupture. Several genes involved in lifespan determination are known regulator of redox cellular balance and pre-clinical evidence underlines their pathophysiological roles in age-related cardiovascular dysfunction and atherosclerosis. Objective: The aim of this narrative review is to examine the impact of aging on arterial function and atherosclerotic plaque development. Furthermore, we report how molecular mechanisms of vascular aging might regulate age-related plaque modifications and how this may help to identify novel therapeutic targets to attenuate the increased risk of CV disease in elderly people.

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Dual Effects of Hearing Loss and Dementia on Functional Limitations in Older Adults

Innovation in Aging ◽

10.1093/geroni/igaa057.690 ◽

2020 ◽

Vol 4 (Supplement_1) ◽

pp. 214-214

Author(s):

Michael McKee ◽

Yunshu Zhou ◽

Joshua Ehrlich ◽

Elham Mahmoudi ◽

Jennifer Deal ◽

...

Keyword(s):

Older Adults ◽

Hearing Loss ◽

Self Care ◽

Household Activity ◽

Cross Sectional ◽

Age Related ◽

Increased Risk ◽

Lower Mobility ◽

Independent Effects ◽

The Impact

Abstract Age-related hearing loss (HL) is both common and associated with elevated risk for cognitive decline and poorer health. To care for an aging population, it is critical to understand the effect of coexisting HL and dementia on functional activities. The effect of co-existing dementia and self-reported HL on daily functioning were assessed. A cross-sectional analysis was performed using nationally-representative data from the 2015 National Health and Aging Trends Study consisting of U.S. adults 65+. The sample included 1,829 adults with HL (22.8%) and 5,338 adults without HL. Multivariable Poisson regression was used to model the independent effects and interaction of self-reported HL and dementia status on three validated functional activity scales (self-care, mobility, and household). All analyses adjusted for sociodemographic and medical factors. HL participants were more likely to be white, older, male, less educated (p <0.01). 8.4% had possible dementia and 6.5% had probable dementia. Respondents with HL or possible or probable dementia had significantly lower mobility, self-care, and household activity scores (p<.001 for all comparisons) compared to their peers. A small yet significant interaction was present in all models, suggesting that HL respondents with co-occurring dementia had lower mobility, self-care, and household activity scores than predicted by the independent effects of dementia and self-reported HL (p<.001 for all comparisons). Older adults with co-occurring dementia and HL are at increased risk for poor functioning and should be screened by healthcare providers. Future work should consider the impact of intervention in this vulnerable/at-risk population.

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Abstract T P136: Potential Contributors to the Declining Impact of Stroke Risk Factors with Age: Implications for Stroke Epidemiology in the Elderly

Stroke ◽

10.1161/str.45.suppl_1.tp136 ◽

2014 ◽

Vol 45 (suppl_1) ◽

Author(s):

George Howard ◽

Mary Cushman ◽

Maciej Banach ◽

Brett M Kissela ◽

David C Goff ◽

...

Keyword(s):

Risk Factors ◽

Risk Factor ◽

Stroke Risk ◽

Multivariable Analysis ◽

The Elderly ◽

Stroke Risk Factors ◽

Age Related ◽

Increased Risk ◽

The Impact ◽

Age Related Changes

Purpose: The importance of stroke research in the elderly is increasing as America is “graying.” For most risk factors for most diseases (including stroke), the magnitude of association with incident events decreases at older ages. Potential changes in the impact of risk factors could be a “true” effect, or could be due to methodological issues such as age-related changes in residual confounding. Methods: REGARDS followed 27,748 stroke-free participants age 45 and over for an average of 5.3 years, during which 715 incident strokes occurred. The association of the “Framingham” risk factors (hypertension [HTN], diabetes, smoking, AFib, LVH and heart disease) with incident stroke risk was assessed in age strata of 45-64 (Young), 65-74 (Middle), and 75+ (Old). For those with and without an “index” risk factor (e.g., HTN), the average number of “other” risk factors was calculated. Results: With the exception of AFib, there was a monotonic decrease in the magnitude of the impact across the age strata, with HTN, diabetes, smoking and LVH even becoming non-significant in the elderly (Figure 1). However, for most factors, the increasing prevalence of other risk factors with age impacts primarily those with the index risk factor absent (Figure 2, example HTN as the “index” risk factor). Discussion: The impact of stroke risk factors substantially declined at older ages. However, this decrease is partially attributable to increases in the prevalence of other risk factors among those without the index risk factor, as there was little change in the prevalence of other risk factors in those with the index risk factor. Hence, the impact of the index risk factor is attenuated by increased risk in the comparison group. If this phenomenon is active with latent risk factors, estimates from multivariable analysis will also decrease with age. A deeper understanding of age-related changes in the impact of risk factors is needed.

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Abstract 1421: In Vivo Measurement of Flow-Mediated Vasodilation in Living Rats using High Resolution Ultrasound: Age-Dependent Endothelial Dysfunction

Circulation ◽

10.1161/circ.116.suppl_16.ii_292-b ◽

2007 ◽

Vol 116 (suppl_16) ◽

Author(s):

Christian Heiss ◽

Richard E Sievers ◽

Nicolas Amabile ◽

Tony Y Momma ◽

Shobha Natarajan ◽

...

Keyword(s):

High Resolution ◽

Endothelial Dysfunction ◽

Endothelial Function ◽

Femoral Artery ◽

Reactive Hyperemia ◽

Surrogate Marker ◽

Flow Measurements ◽

Age Related ◽

Age Dependent

In humans, endothelial function serves as a surrogate marker for cardiovascular health and is measured as changes in arterial diameter after temporary ischemia (flow-mediated dilation; FMD). We developed an FMD-related approach to study conduit artery vasodilation in living rats, and demonstrate a reduction in FMD in older versus younger animals consistent with age-related endothelial dysfunction. Diameter and Doppler-flow measurements were obtained from the femoral artery using high-resolution ultrasound (35 MHz). We observed dose-dependent vasodilation using both endothelium-dependent and endothelium-independent pharmacologic vasodilators (acetylcholine and nitroglycerine). Flow-dependent vasodilation was observed in response to flow increase induced both by adenosine and local saline infusion. Transient hindlimb ischemia led to reactive hyperemia with sequential flow velocity increase and femoral artery dilation, the latter of which was completely abolished by NO-synthase (NOS) inhibition with L-NMMA. To demonstrate its applicability in a model of endothelial dysfunction, we show that FMD is significantly reduced in older versus younger animals. While FMD was completely NOS-dependent in younger animals, NOS-dependent mechanisms accounted for only half of the FMD in older animals, with the remainder being blocked by charybdotoxin (CTx) and apamin suggesting contribution of endothelium-derived-hyperpolarizing-factor. Using this new integrative physiologic model to reproducibly study FMD in living rats, we show that age-dependent endothelial dysfunction is accompanied by a shift in mechanisms underlying vasodilatory endothelial function.

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Age-Related Differences in Experiences With Social Distancing at the Onset of the COVID-19 Pandemic: A Computational and Content Analytic Investigation of Natural Language From a Social Media Survey (Preprint)

10.2196/preprints.26043 ◽

2020 ◽

Author(s):

Ryan C Moore ◽

Angela Y Lee ◽

Jeffrey T Hancock ◽

Meghan C Halley ◽

Eleni Linos

Keyword(s):

Public Health ◽

Age Groups ◽

Prevention Measures ◽

Middle Aged ◽

Social Distancing ◽

Aged People ◽

Age Related ◽

Health Related ◽

The Impact ◽

Health Guidance

BACKGROUND As COVID-19 poses different levels of threat to people of different ages, health communication regarding prevention measures such as social distancing and isolation may be strengthened by understanding the unique experiences of various age groups. OBJECTIVE The aim of this study was to examine how people of different ages (1) experienced the impact of the COVID-19 pandemic and (2) their respective rates and reasons for compliance or noncompliance with social distancing and isolation health guidance. METHODS We fielded a survey on social media early in the pandemic to examine the emotional impact of COVID-19 and individuals’ rates and reasons for noncompliance with public health guidance, using computational and content analytic methods of linguistic analysis. RESULTS A total of 17,287 participants were surveyed. The majority (n=13,183, 76.3%) were from the United States. Younger (18-31 years), middle-aged (32-44 years and 45-64 years), and older (≥65 years) individuals significantly varied in how they described the impact of COVID-19 on their lives, including their emotional experience, self-focused attention, and topical concerns. Younger individuals were more emotionally negative and self-focused, while middle-aged people were other-focused and concerned with family. The oldest and most at-risk group was most concerned with health-related terms but were lower in anxiety (use of fewer anxiety-related terms) and higher in the use of emotionally positive terms than the other less at-risk age groups. While all groups discussed topics such as acquiring essential supplies, they differentially experienced the impact of school closures and limited social interactions. We also found relatively high rates of noncompliance with COVID-19 prevention measures, such as social distancing and self-isolation, with younger people being more likely to be noncompliant than older people (<i>P</i><.001). Among the 43.1% (n=7456) of respondents who did not fully comply with health orders, people differed substantially in the reasons they gave for noncompliance. The most common reason for noncompliance was not being able to afford to miss work (n=4273, 57.3%). While work obligations proved challenging for participants across ages, younger people struggled more to find adequate space to self-isolate and manage their mental and physical health; middle-aged people had more concerns regarding childcare; and older people perceived themselves as being able to take sufficient precautions. CONCLUSIONS Analysis of natural language can provide insight into rapidly developing public health challenges like the COVID-19 pandemic, uncovering individual differences in emotional experiences and health-related behaviors. In this case, our analyses revealed significant differences between different age groups in feelings about and responses to public health orders aimed to mitigate the spread of COVID-19. To improve public compliance with health orders as the pandemic continues, health communication strategies could be made more effective by being tailored to these age-related differences.

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Middle-Aged Indians with Type 2 Diabetes Are at Higher Risk of Biological Ageing with Special Reference to Serum CDKN2A

Journal of Diabetes Research ◽

10.1155/2020/7569259 ◽

2020 ◽

Vol 2020 ◽

pp. 1-10

Author(s):

Joyita Banerjee ◽

Yogita Dhas ◽

Neetu Mishra

Keyword(s):

Oxidative Stress ◽

Type 2 Diabetes ◽

Special Reference ◽

Oxidized Ldl ◽

Middle Aged ◽

Biological Ageing ◽

Proinflammatory Mediators ◽

Age Related ◽

Increased Risk

Sedentary lifestyle and high visceral adiposity have elevated the risk of type 2 diabetes (T2DM) among Indians at younger age. In this study, we aimed to investigate the association of oxidative stress and chronic inflammatory mediators with ageing with special reference to the biological ageing marker cyclin-dependent kinase inhibitor 2A (CDKN2A) among middle-aged (31-50 years) Indian healthy and T2DM subjects. Malondialdehyde (MDA), oxidized LDL (oxLDL), interleukin-6 (IL-6), interleukin 1β (IL-1β), tumor necrosis factor α (TNF-α), monocyte chemoattractant protein-1 (MCP-1), and CDKN2A were measured in T2DM patients (n=80) and controls (n=80) aged 31-50 years, further grouped into G1: 31-40 years and G2: 41-50 years. IL-6, TNF-α, MCP-1, and CDKN2A showed a significant association with ageing among both T2DM patients and controls. But the strength of the association of MCP-1 and CKDN2A with ageing was significantly stronger in T2DM patients than the controls. All the oxidative stress and proinflammatory mediators showed nonsignificant associations with CDKN2A in the controls. However, IL-6, TNF-α, and MCP-1 showed a strong association with CDKN2A in T2DM patients. An increased risk of high levels of CDKN2A was found in G1 T2DM patients (OR: 3.484 (95% CI: 1.246-9.747) p=0.017) and G2 T2DM patients (OR: 5.000 (95% CI: 1.914-13.061), p=0.001) with reference to the respective control groups. Our study reveals that the middle-aged Indians with T2DM are at higher risk of biological ageing. The development of T2DM is more common among middle-aged Indians. T2DM may exacerbate the ageing process and may subsequently predispose Indians to various age-related complications at a much early age.

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Lower human defensin 5 in elderly people compared to middle-aged is associated with differences in the intestinal microbiota composition: the DOSANCO Health Study

GeroScience ◽

10.1007/s11357-021-00398-y ◽

2021 ◽

Author(s):

Yu Shimizu ◽

Kiminori Nakamura ◽

Mani Kikuchi ◽

Shigekazu Ukawa ◽

Koshi Nakamura ◽

...

Keyword(s):

Elderly People ◽

Intestinal Microbiota ◽

Disease Risk ◽

Paneth Cell ◽

The Elderly ◽

Microbiota Composition ◽

Middle Aged ◽

Age Related ◽

Increased Risk ◽

Human Defensin 5

AbstractRecently, aging is considered a risk factor for various diseases. Although changes in the intestinal microbiota along with aging are thought to associate with the increased disease risk, mechanisms that cause age-related transition of the intestinal microbiota remain unknown. This study aims to clarify relationships between the amount of human defensin 5 (HD5), a Paneth cell α-defensin, which is known to regulate the intestinal microbiota, and age-related differences of the intestinal microbiota composition. Fecal samples from 196 healthy Japanese (35 to 81 years old) were collected and measured HD5 concentration. HD5 concentration in the elderly group (age > 70 years old) was significantly lower than the middle-aged group (age ≤ 70 years old). Furthermore, individual age was negatively correlated with HD5 concentration (r = − 0.307, p < 0.001). In β-diversity, the intestinal microbiota of the elderly showed a significantly different composition compared to the middle-aged. At the genus level, relative abundance of Collinsella, Alistipes, Peptococcaceae; unassigned, Lactobacillus, Lactococcus, Weissella, Christensenellaceae R-7 group, Megasphaera, and [Eubacterium] eligens group was significantly higher, and Lachnospiraceae; unassigned, Blautia, Anaerostipes, Fusicatenibacter, Dorea, and Faecalibacterium was significantly lower in the elderly compared to the middle-aged. In addition, HD5 concentration was negatively correlated with Alistipes, Peptococcaceae; unassigned, and Christensenellaceae R-7 group and positively correlated with Lachnospiraceae; unassigned and Dorea. These results provide novel insights into the immunosenescence of enteric innate immunity, indicating low HD5 is suggested to contribute to the age-related differences in the intestinal microbiota and may relate to increased risk of diseases in elderly people.

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Metabolomic profiling of serum in aging mice supplemented with tocotrienol-rich fraction for identification of female reproductive aging biomarkers

Malaysian Journal of Fundamental and Applied Sciences ◽

10.11113/mjfas.v14n4.1132 ◽

2018 ◽

Vol 14 (4) ◽

pp. 467-470

Author(s):

Norrabiátul Adawiyah Aziz ◽

Fathimah Mohamad ◽

Teh Lay Kek ◽

Nuraliza Abdul Satar

Keyword(s):

Oxidative Stress ◽

Ovarian Function ◽

Corn Oil ◽

Negative Impact ◽

Protective Mechanism ◽

Reproductive Aging ◽

Cell Stage ◽

Age Related ◽

Tocotrienol Rich Fraction ◽

The Impact

Ovarian aging has been associated with increased oxidative stress leading to loss of ovarian function and infertility. Tocotrienol, a potent antioxidant, has been proven to exert beneficial effects in the female reproductive system. Serum metabolites were analyzed to examine the biochemical changes and to identify biomarkers related to reproductive aging that could lead to poor embryo quality and development. Female Mus musculus mice were divided into four groups. Six-month-old mice were given tocopherol-stripped corn oil as a vehicle control while other groups were supplemented orally with tocotrienol-rich fraction (TRF) at doses of 90, 120, and 150 mg/kg bodyweight for two months, respectively. After two months, mice from all groups were super ovulated, and euthanized. Embryos were collected at the 2-cell stage and cultured to monitor their development while serum was used for metabolomic analysis. The percentage of normal embryos and development of embryos to blastocyst stage were significantly higher in groups supplemented with TRF. A total of 71 metabolites that are related to reproductive aging were identified in all groups and significant changes were detected in metabolic pathways that include fatty acids, amino acids metabolism and steroid hormone biosynthesis. These changes suggest that aging has a negative impact on cellular energy storage, energy metabolism and oxidative stress that subsequently affect female fertility. Supplementation with TRF prevented the impact of age related metabolic changes on the embryo. Thus, it appears that TRF exerts a protective mechanism towards female reproductive aging.

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Estimating the Risks from COVID-19 Infection in Adult Chemotherapy Patients

10.1101/2020.03.18.20038067 ◽

2020 ◽

Cited By ~ 3

Author(s):

Matt Williams ◽

Kerlann Le Calvez ◽

Ella Mi ◽

Jiarong Chen ◽

Seema Dadhania ◽

...

Keyword(s):

Case Fatality ◽

Related Case ◽

Additional Risk ◽

Risk Of Death ◽

Age Related ◽

Increased Risk ◽

Chemotherapy Patients ◽

Influenza Outbreaks ◽

Rich Countries ◽

The Impact

AbstractThe SARS-CoV-2 (COVID-19) novel corona virus represents a significant health risk, particularly in older patients. Cancer is one of the leading causes of death in most rich countries, and delivering chemotherapy may be associated with increased risk in the presence of a pandemic infection. Estimating this risk is crucial in making decisions about balancing risks and benefits from administering chemotherapy. However, there are no specific data about chemotherapy risks per se. Here we develop a simple model to estimate the potential harms in patients undergoing chemotherapy during a COVID outbreak. We use age-related case fatality rates as a basis for estimating risk, and use previous data from risk of death during influenza outbreaks to estimate the additional risk associated with chemotherapy. We use data from randomised trials to estimate benefit across a range of curative and palliative settings, and address the balance of benefit against the risk of harm. We then use those data to estimate the impact on national chemotherapy delivery patterns.

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Balance training and visual rehabilitation of age-related macular degeneration patients

Journal of Vestibular Research ◽

10.3233/ves-2007-17404 ◽

2008 ◽

Vol 17 (4) ◽

pp. 183-193

Author(s):

Xavier Radvay ◽

Stéphanie Duhoux ◽

Françoise Koenig-Supiot ◽

François Vital-Durand

Keyword(s):

Macular Degeneration ◽

Balance Control ◽

Reading Speed ◽

Balance Training ◽

Age Related Macular Degeneration ◽

Control Group ◽

Age Related ◽

Increased Risk ◽

Pointing Accuracy ◽

The Impact

Patients with Age-Related Macular Degeneration (AMD) experience a large scotoma precluding central vision. In addition, 2/3 of these patients present visuomotor and balance deficits resulting in clumsiness and increased risk of falls. On the basis of previous work demonstrating that visual, vestibular and somatosensory functions involved in balance control can be rehabilitated by training, we attempted to improve these functions by balance training. We measured the impact of balance training on several visuomotor functions and reading speed. We compared balance status of 54 AMD patients to 55 normal controls. Sixteen of these patients and 14 controls subsequently received balance training sessions on a postural platform (Multitest®) stressing sensorimotor coordination by selectively inhibiting or disturbing either, visual, vestibular or somatosensory input. Producing a conflict between two inputs reinforces the use of the third. We assessed postural sway, pointing accuracy, reading performance and, for the patients, the effect of low vision training and balance training on the shift from several spontaneous Preferred Retinal Loci (PRLs) to one or more Trained Retinal Loci (TRL). Even after a limited number of sessions of cross-modal balance training, the results show a significant improvement for the vestibular input and fixation stability. A decrease of visual dependency was observed only in the control group. Apart from these improvements, pointing accuracy and reading speed were not significantly improved compared to controls, leading to the conclusion that more training sessions may be necessary to gain more significant improvement of visuo-motor functions.

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