scholarly journals Decoding the transcriptional response to ischemic stroke in young and aged mouse brain

2019 ◽  
Author(s):  
Peter Androvic ◽  
Denisa Belov Kirdajova ◽  
Jana Tureckova ◽  
Daniel Zucha ◽  
Eva Rohlova ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Expression Analysis ◽  
Temporal Dynamics ◽  
Age Groups ◽  
Transcriptional Response ◽  
Cell Types ◽  
Selective Vulnerability ◽  
Type I ◽  
Aged Mouse ◽  
Age Related

AbstractIschemic stroke is one of the leading causes of mortality and major healthcare and economic burden. It is a well-recognized disease of aging, yet it is unclear how the age-dependent vulnerability occurs and what are the underlying mechanisms. To address these issues, we performed a comprehensive RNA-Seq analysis of aging, ischemic stroke and their interaction using a model of permanent middle cerebral artery occlusion (MCAO) in 3 and 18 month old female mice. We assessed differential gene expression across injury status and age, estimated cell type proportion changes, assayed the results against a range of transcriptional signatures from the literature and performed unsupervised co-expression analysis, identifying modules of genes with varying response to injury. We uncovered selective vulnerability of neuronal populations and increased activation of type-I interferon (IFN-I) signaling and several other inflammatory pathways in aged mice. We extended these findings via targeted expression analysis in tissue as well as acutely purified cellular populations to show differential temporal dynamics of IFN-I signaling between age groups and contribution of individual cell types. Together, these results paint a picture of ischemic stroke as a complex age-related disease and provide insights into interaction of aging and stroke on cellular and molecular level.Graphical summary

Maximal lactate steady state declines during the aging process

2003 ◽  
Vol 95 (6) ◽  
pp. 2576-2582 ◽  
Author(s):  
Craig O. Mattern ◽  
Margaret J. Gutilla ◽  
Darrin L. Bright ◽  
Timothy E. Kirby ◽  
Kenneth W. Hinchcliff ◽  
...  
Keyword(s):  
Steady State ◽  
Exercise Intensity ◽  
Citrate Synthase ◽  
Age Groups ◽  
Type I ◽  
Training Intensity ◽  
Maximal Lactate Steady State ◽  
Age Related ◽  
Competitive Cyclists ◽  
Age Related Changes

Increased participation of aged individuals in athletics warrants basic research focused on delineating age-related changes in performance variables. On the basis of potential age-related declines in aerobic enzyme activities and a shift in the expression of myosin heavy chain (MHC) isoforms, we hypothesized that maximal lactate steady-state (MLSS) exercise intensity would be altered as a function of age. Three age groups [young athletes (YA), 25.9 ± 1.0 yr, middle-age athletes (MA), 43.2 ± 1.0 yr, and older athletes (OA), 64.6 ± 2.7 yr] of male, competitive cyclists and triathletes matched for training intensity and duration were studied. Subjects performed a maximal O2 consumption (V̇o2 max) test followed by a series of 30-min exercise trials to determine MLSS. A muscle biopsy of the vastus lateralis was procured on a separate visit. There were differences ( P < 0.05) in V̇o2 max among all age groups (YA = 67.7 ± 1.2 ml · kg-1 · min-1, MA = 56.0 ± 2.6 ml · kg-1 · min-1, OA = 47.0 ± 2.6 ml · kg-1 · min-1). When expressed as a percentage of V̇o2 max, there was also an age-related decrease ( P < 0.05) in the relative MLSS exercise intensity (YA = 80.8 ± 0.9%, MA = 76.1 ± 1.4%, OA = 69.9 ± 1.5%). There were no significant age-related changes in citrate synthase activity or MHC isoform profile. The hypothesis is supported as there is an age-related decline in MLSS exercise intensity in athletes matched for training intensity and duration. Although type I MHC isoform, combined with age, is helpful in predicting ( r = 0.76, P < 0.05) relative MLSS intensity, it does not explain the age-related decline in MLSS.

scholarly journals Age-related histochemical investigations of small intestinal goblet cells in bronze turkeys (Meleagris gallopavo gallopavo)

2021 ◽  
Vol 24 (2) ◽  
pp. 176-183
Author(s):  
D. Yovchev ◽  
G. Penchev
Keyword(s):  
Small Intestine ◽  
Age Groups ◽  
Negative Relationship ◽  
Meleagris Gallopavo ◽  
Cell Types ◽  
Goblet Cells ◽  
Age Related ◽  
Pas Staining ◽  
Small Intestinal ◽  
Acid Mucins

The aim of the study was to investigate the goblet cell types and their density in the small intestine of bronze turkey (Meleagris meleagris gallopovo), by means of Alcian blue-PAS staining. Sixty birds from 10 age groups were used. In the duodenum and jejunum, goblet cells produced acid, neutral and mixed mucins, while in the jejunum - acid mucins. A negative relationship was observed between cell density and either duodenum or jejunum lengths; such a correlation was not established in the ileum.

Effects of aging and obesity on respiratory muscle phenotype in Zucker rats

1996 ◽  
Vol 81 (3) ◽  
pp. 1347-1354 ◽  
Author(s):  
S. K. Powers ◽  
G. A. Farkas ◽  
H. Demirel ◽  
J. Coombes ◽  
L. Fletcher ◽  
...  
Keyword(s):  
Respiratory Muscle ◽  
Citrate Synthase ◽  
Work Of Breathing ◽  
Age Groups ◽  
Respiratory Muscles ◽  
Oxidative Capacity ◽  
Zucker Rats ◽  
Type I ◽  
Inspiratory Muscles ◽  
Age Related

Because obesity results in an increased work of breathing, we tested the hypothesis that the oxidative properties and myosin heavy chain (MHC) isoform profiles in respiratory muscles would differ between lean and obese animals. Furthermore, we postulated that obesity-related changes in respiratory muscles would be independent of age. To test these hypothesis, samples of the costal diaphragm, crural diaphragm, and parasternal intercostal muscles were removed from three age groups (young, adult, and old) of obese and lean Zucker rats. Citrate synthase (CS) activity was measured as a marker of oxidative capacity, and MHC isoforms were identified with gel electrophoresis. Analysis revealed that CS activity was significantly higher in the crural and costal diaphragms and parasternal intercostal of obese animals compared with lean animals (P < 0.05); this obesity-related increased in CS activity was related independent of age. Furthermore, respiratory muscle percent type IIb MHC was lower and percent type I MHC isoforms were higher in obese animals compared with lean animals. These data support the notion that obesity results in a fast-to-slow shift in MHC phenotype and an increase in oxidative capacity in major inspiratory muscles. The shift in MHC isoforms in obese animals is also age related, whereas the obesity-mediated increase in oxidative capacity is relatively independent of age.

scholarly journals Chromatin alterations in the aging lung change progenitor cell activity

2021 ◽  
Author(s):  
Samuel P. Rowbotham ◽  
Patrizia Pessina ◽  
Carolina Garcia de Alba Rivas ◽  
Jingyun Li ◽  
Irene Wong ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Progenitor Cell ◽  
Cell Activity ◽  
Cell Types ◽  
Chromatin Accessibility ◽  
Alveolar Type ◽  
Aged Mouse ◽  
Efficient Manner ◽  
Age Related ◽  
Multipotent Progenitor Cells

The lung contains multiple progenitor cell types that respond to damage, but how their responses are choreographed and why they decline with age is poorly understood. We report that histone H3 lysine 9 di-methylation (K9me2), mediated by histone methyltransferase G9a, regulates the dynamics of lung epithelial progenitor cells, and this regulation deteriorates with age. In aged mouse lungs, K9me2 loss coincided with lower frequency and activity of alveolar type 2 (AT2) cell progenitors. In contrast, K9me2 loss resulted in increased frequency and activity of multipotent progenitor cells with bronchiolar and alveolar potential (BASCs) and bronchiolar progenitors. K9me2 depletion in young mice through deletion or inhibition of G9a decreased AT2 progenitor activity and impaired alveolar injury regeneration. Conversely, K9me2 depletion increased chromatin accessibility of bronchiolar cell genes, increased BASC frequency and accelerated bronchiolar repair. K9me2 depletion also resulted in increased bronchiolar cell expression of the SARS-CoV2 receptor Ace2 in aged lungs. These data point to K9me2 and G9a as a critical regulator of the balance of lung progenitor cell regenerative responses and prevention of susceptibility to age-related lung diseases. These findings indicate that epigenetic regulation coordinates progenitor cell populations to expedite regeneration in the most efficient manner and disruption of this regulation presents significant challenges to lung health.

scholarly journals Decoding the Transcriptional Response to Ischemic Stroke in Young and Aged Mouse Brain

Cell Reports ◽  
2020 ◽  
Vol 31 (11) ◽  
pp. 107777
Author(s):  
Peter Androvic ◽  
Denisa Kirdajova ◽  
Jana Tureckova ◽  
Daniel Zucha ◽  
Eva Rohlova ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Mouse Brain ◽  
Transcriptional Response ◽  
Aged Mouse ◽  
Stroke In Young

Abstract WMP50: Age-Specific Female-Male Disparities in Endovascular Thrombectomy Use for Acute Ischemic Stroke in the United States

Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Hamidreza Saber ◽  
Amytis Towfighi ◽  
David S Liebeskind ◽  
Jeffrey L Saver
Keyword(s):  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Age Groups ◽  
Reperfusion Therapy ◽  
The United States ◽  
National Inpatient Sample ◽  
Endovascular Thrombectomy ◽  
Age Related ◽  
The Us ◽  
Age And Sex

Introduction: Studies have suggested sex-related and age-related variations in frequency of reperfusion therapy, but have been limited by constrained geographic scope, data from before the modern thrombectomy era, and incomplete exploration of sex-related differences in discrete age ranges. We therefore analyzed sex-, age-, and sex-age interaction in the frequency of endovascular thrombectomy (EVT) for acute ischemic stroke in the US National Inpatient Sample. Methods: In the National Inpatient Sample , we identified all adult ischemic stroke EVT hospitalizations from 2010-2016, using ICD-9-CM and ICD-10-CM codes. Patient age was categorized as: <50y, 50-59y, 60-69y, 70-79y and ≥80ys. Rates of use of EVT were assessed standardized to the 2010 US Census population. Results: Among 50,573 EVT hospitalizations, 50.1% were female. The number of EVTs increased from 4091 in 2010 to 12,875 in 2016. Over the entire 7y time period, a sex-age interaction was noted: 49% in <50y; 37% in 50-59y; 35% in 60-69y; 53% in 70-79y; and 66% in ≥80y. This sex-age interaction was present as well for EVT rates per 100,000 individuals in the population, with the total ratio of female to male rate of EVT per 100,000: 0.93 for in <50y; 0.52 in 50-59y; 0.58 in 60-69y; 0.91 in 70-79y; and 1.1 in ≥80y. EVT utilization rates increased substantially over time in both men and women in all age groups. However, the ratio of women to men per 100,000 receiving EVT changed for only one age range, decreasing among <50y from 0.98 in 2010 to 0.79 in 2016 (P<0.05). Conclusion: While half of all endovascular thrombectomies in the US are performed in women, there are major age-related sex-specific variations in EVT rates, with rates of EVT much lower among women than men in 50-70 age group. Determinants of these age-specific female-male disparities in EVT treatment merit detailed investigation. Figure: Age- and sex-specific female to male thrombectomy utilization rates.

scholarly journals Age-Related Expression of IFN-λ1 Versus IFN-I and Beta-Defensins in the Nasopharynx of SARS-CoV-2-Infected Individuals

2021 ◽  
Vol 12 ◽  
Author(s):  
Charly Gilbert ◽  
Caroline Lefeuvre ◽  
Laurence Preisser ◽  
Adeline Pivert ◽  
Raffaella Soleti ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Expression Patterns ◽  
Age Groups ◽  
The Elderly ◽  
Surfactant Protein ◽  
Innate Immune ◽  
Surfactant Protein D ◽  
Type I ◽  
Mrna Levels ◽  
Age Related

SARS-CoV-2 coronavirus infection induces heterogeneous symptoms, ranging from asymptomatic to lethal forms. Severe forms usually occur in the elderly and/or individuals with comorbidities. Children generally remain asymptomatic to primary infection, suggesting that they may have an effective local innate immune response. IFN-I and -III have non-redundant protective roles against SARS-CoV-2, although sometimes damaging the host. The expression and role of anti-viral peptides during SARS-CoV-2 infection have thus far been little studied. We aimed to identify the innate immune molecules present at the SARS-CoV-2 entry point. We analyzed the mRNA levels of type I (IFN-α and -β) and type III (IFN-λ1-3) interferons and selected antiviral peptides (i.e., β-defensins 1-3, α-defensins [HNP1-3, HD5] pentraxin-3, surfactant protein D, the cathelicidin LL-37 and interleukin-26) in nasopharyngeal swabs from 226 individuals of various ages, either infected with SARS-CoV-2 (symptomatic or asymptomatic) or negative for the virus. We observed that infection induced selective upregulation of IFN-λ1 expression in pediatric subjects (≤15 years), whereas IFN-α, IFN-β, IFN-λ2/λ3, and β-defensin 1-3 expression was unaffected. Conversely, infection triggered upregulation of IFN-α, IFN-β, IFN-λ2/λ3, and β-defensin 1-3 mRNA expression in adults (15-65 years) and the elderly (≥ 65 years), but without modulation of IFN-λ1. The expression of these innate molecules was not associated with gender or symptoms. Expression of the interferon-stimulated genes IFITM1 and IFITM3 was upregulated in SARS-CoV-2-positive subjects and reached similar levels in the three age groups. Finally, age-related differences in nasopharyngeal innate immunity were also observed in SARS-CoV-2-negative subjects. This study shows that the expression patterns of IFN-I/-III and certain anti-viral molecules in the nasopharyngeal mucosa of SARS-CoV-2-infected subjects differ with age and suggests that susceptibility to SARS-CoV-2 may be related to intrinsic differences in the nature of mucosal anti-viral innate immunity.

scholarly journals Inflammatory pathways are central to posterior cerebrovascular artery remodelling prior to the onset of congenital hypertension

2018 ◽  
Vol 39 (9) ◽  
pp. 1803-1817 ◽  
Author(s):  
Dawid Walas ◽  
Karol Nowicki-Osuch ◽  
Dominic Alibhai ◽  
Eva von Linstow Roloff ◽  
Jane Coghill ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Cerebral Artery ◽  
Collagen Type ◽  
Cerebral Arteries ◽  
Systemic Blood Pressure ◽  
Collagen Type I ◽  
Protective Mechanism ◽  
Type I ◽  
Age Related ◽  
Second Harmonics Generation

Cerebral artery hypoperfusion may provide the basis for linking ischemic stroke with hypertension. Brain hypoperfusion may induce hypertension that may serve as an auto-protective mechanism to prevent ischemic stroke. We hypothesised that hypertension is caused by remodelling of the cerebral arteries, which is triggered by inflammation. We used a congenital rat model of hypertension and examined age-related changes in gene expression of the cerebral arteries using RNA sequencing. Prior to hypertension, we found changes in signalling pathways associated with the immune system and fibrosis. Validation studies using second harmonics generation microscopy revealed upregulation of collagen type I and IV in both tunica externa and media. These changes in the extracellular matrix of cerebral arteries pre-empted hypertension accounting for their increased stiffness and resistance, both potentially conducive to stroke. These data indicate that inflammatory driven cerebral artery remodelling occurs prior to the onset of hypertension and may be a trigger elevating systemic blood pressure in genetically programmed hypertension.

scholarly journals Getting on in Old Age: How the Gut Microbiota Interferes With Brain Innate Immunity

2021 ◽  
Vol 15 ◽  
Author(s):  
Omar Mossad ◽  
Thomas Blank
Keyword(s):  
Immune Response ◽  
Innate Immunity ◽  
Immune System ◽  
Gut Microbiota ◽  
Inflammatory Diseases ◽  
Cell Types ◽  
Innate Immune ◽  
Type I Interferons ◽  
Type I ◽  
Age Related

The immune system is crucial for defending against various invaders, such as pathogens, cancer cells or misfolded proteins. With increasing age, the diminishing immune response, known as immunosenescence, becomes evident. Concomitantly, some diseases like infections, autoimmune diseases, chronic inflammatory diseases and cancer, accumulate with age. Different cell types are part of the innate immunity response and produce soluble factors, cytokines, chemokines, and type I interferons. Improper maturation of innate immune cells or their dysfunction have been linked to numerous age-related diseases. In parallel to the occurrence of the many functional facets of the immune response, a symbiotic microbiota had been acquired. For the relevant and situation-dependent function of the immune system the microbiome plays an essential role because it fine-tunes the immune system and its responses during life. Nevertheless, how the age-related alterations in the microbiota are reflected in the innate immune system, is still poorly understood. With this review, we provide an up-to-date overview on our present understanding of the gut microbiota effects on innate immunity, with a particular emphasis on aging-associated changes in the gut microbiota and the implications for the brain innate immune response.

Aging and Error Processing

2005 ◽  
Vol 19 (4) ◽  
pp. 289-297 ◽  
Author(s):  
Vasil Kolev ◽  
Michael Falkenstein ◽  
Juliana Yordanova
Keyword(s):  
Temporal Dynamics ◽  
Age Groups ◽  
Reaction Time Task ◽  
Error Processing ◽  
Frequency Content ◽  
Common Error ◽  
Time Frequency ◽  
Age Related ◽  
Related Potentials ◽  
Older Subjects

Abstract: Objectives: To determine age-related changes in the frequency content, temporal dynamics, and functional reactivity of error-related potentials. Methods: Two groups of subjects, young (mean age 22.5 years) and older (mean age 58.3 years) were studied with a four-choice reaction time task. Response-related potentials (RRPs) to correct and error responses were decomposed by means of wavelet transform. Time-frequency (TF) components of correct and error responses were identified. Effects of aging were evaluated for the phase-locked TF power at FCz. Results: (1) Error-related potentials in both groups were characterized by phase-locked activity from the delta (1.5-3.5 Hz) frequency band that was error-specific and was significantly enhanced for errors. (2) In contrast to young adults, no pronounced phase-locked theta (4-7 Hz) RRP components were generated at FCz for either correct or error responses, nor did the theta power manifest any sensitivity to error processing in older subjects. Conclusion: In older subjects, RRPs at FCz do not contain a theta TF component, thus, demonstrating that the frequency content of error-related potentials changes with aging. A common error-specific delta component is present in the two age groups, but its reactivity is significantly reduced and delayed with aging. These qualitative and quantitative differences between young and older subjects may reflect a functional suppression of the underlying frontomedial structures involved in performance and movement monitoring.

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