Effects of aging on protein expression in mice brain microvessels: ROS scavengers, mRNA/protein stability, glycolytic enzymes, mitochondrial complexes, and basement membrane components

AbstractDifferentially expressed (DE) proteins in the cortical microvessels (MVs) of young, middle-aged, and old male and female mice were evaluated using discovery-based proteomics analysis (> 4,200 quantified proteins/group). Most DE proteins (> 90%) showed no significant differences between the sexes; however, some significant DE proteins showing sexual differences in MVs decreased from young (8.3%), to middle-aged (3.7%), to old (0.5%) mice. Therefore, we combined male and female data for age-dependent comparisons but noted sex differences for examination. Key proteins involved in the oxidative stress response, mRNA or protein stability, basement membrane (BM) composition, aerobic glycolysis, and mitochondrial function were significantly altered with aging. Relative abundance of superoxide dismutase-1/-2, catalase and thioredoxin were reduced with aging. Proteins participating in either mRNA degradation or pre-mRNA splicing were significantly increased in old mice MVs, whereas protein stabilizing proteins decreased. Glycolytic proteins were not affected in middle age, but the relative abundance of these proteins decreased in MVs of old mice. Although most of the 41 examined proteins composing mitochondrial complexes I–V were reduced in old mice, six of these proteins showed a significant reduction in middle-aged mice, but the relative abundance increased in fourteen proteins. Nidogen, collagen, and laminin family members as well as perlecan showed differing patterns during aging, indicating BM reorganization starting in middle age. We suggest that increased oxidative stress during aging leads to adverse protein profile changes of brain cortical MVs that affect mRNA/protein stability, BM integrity, and ATP synthesis capacity.

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CLINICAL CHARACTERISTICS OF MEN AND WOMEN IN YOUNG AND MIDDLE AGE WITH ARTERIAL HYPERTENSION AT DIFFERENT GALECTIN-3 PLASMA LEVELS ACCORDING TO THE RESULT OF LINEAR REGRESSION ANALYSIS

EUREKA Health Sciences ◽

10.21303/2504-5679.2019.001072 ◽

2019 ◽

Vol 6 ◽

pp. 35-41

Author(s):

Valeriy Ivanov ◽

Tetiana Onyshchuk

Keyword(s):

Regression Analysis ◽

Linear Regression ◽

Arterial Hypertension ◽

Multiple Linear Regression ◽

Plasma Levels ◽

Middle Age ◽

Middle Aged ◽

Male And Female ◽

Female Patients ◽

Galectin 3

The aim of the research was to describe the clinical charachters of male and female patients with stage II arterial hypertension (AH) of young and middle age with different gradations of galectin-3 plasma levels according to multiple linear stepwise regression analysis. Materials and methods: 160 patients with AH of different sex (male and female) and age (young (18–44 years), middle (45–60 years)) were examined (clinical, laboratory and instrumental). Multiple linear regression was used to determine the clinical presentation of patients with AH at different levels of the neurohormone (StatSoft's Statistica MultipleRegression v. 10.0 module). which were divided into groups that vi told for the entirely different patient characteristics. multiple linear regression was performed for each indicator separately and the results have been shaped in the form of regression equations. Results. Patients with young and middle-aged AH have been found to be relatively high (RH) levels of galectin-3 associated with: the presence of a complex of metabolic risk factors – obesity and dyslipidemia; in combination with multiple features of structural and functional changes in the cardiovascular system, such as the presence of concentric left ventricular (LV) hypertrophy in combination with myocardial relaxation disorders (Е/e' aver>7.2) and signs of hemodynamic overload of the left atrium (LA) (LA volume index (LAVi)>34 ml/m2); the presence of valve dysfunctions in the form of mitral (1–2 degree) and aortic regurgitation (1 stage); the presence of structural remodeling of the carotid arteries (intima-media thickness (IMT)>0.91 mm). Plasma abdominal obesity was the most informative marker of RH galectin-3 in plasma, IMT>0.91 mm and LAVi>34 ml/m2. Conclusions. The association of plasma galectin-3 levels with various clinical and instrumental indicators indicates a certain effect of the neurohormone on the course of AH in young and middle-aged male and female patients. Of indisputable interest is the determination of the features of the course of AH and the clinical profile of patients at different gradations (relatively low (RL), relatively moderate (RM) and relatively high (RH)) galectin-3 plasma level.

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Androgens Enhance Adult Hippocampal Neurogenesis in Males but Not Females in an Age-Dependent Manner

Endocrinology ◽

10.1210/en.2019-00114 ◽

2019 ◽

Vol 160 (9) ◽

pp. 2128-2136 ◽

Cited By ~ 10

Author(s):

Paula Duarte-Guterman ◽

Stephanie E Lieblich ◽

Steven R Wainwright ◽

Carmen Chow ◽

Jessica A Chaiton ◽

...

Keyword(s):

Middle Age ◽

Hippocampal Neurogenesis ◽

Adult Hippocampal Neurogenesis ◽

Female Rats ◽

Male Rats ◽

Dependent Manner ◽

Middle Aged ◽

Male And Female ◽

Male And Female Rats ◽

Age Dependent

Abstract Androgens (testosterone and DHT) increase adult hippocampal neurogenesis by increasing survival of new neurons in male rats and mice via an androgen receptor pathway, but it is not known whether androgens regulate neurogenesis in female rats and whether the effect is age-dependent. We investigated the effects of DHT, a potent androgen, on neurogenesis in young adult and middle-aged male and female rats. Rats were gonadectomized and injected with the DNA synthesis marker bromodeoxyuridine (BrdU). The following day, rats began receiving daily injections of oil or DHT for 30 days. We evaluated cell proliferation (Ki67) and survival of new neurons (BrdU and BrdU/NeuN) in the hippocampus of male and female rats by using immunohistochemistry. As expected, DHT increased the number of BrdU+ cells in young males but surprisingly not in middle-aged males or in young and middle-aged females. In middle age, DHT increased the proportion of BrdU/NeuN cells, an effect driven by females. Androgen receptor expression also increased with aging in both female and male rats, which may contribute to a lack of DHT neurogenic effect in middle age. Our results indicate that DHT regulates adult hippocampal neurogenesis in a sex- and age-dependent manner.

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The blister of porphyria cutanea tarda: A Scanning and Transmission Electron Microscopic study

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100143298 ◽

1986 ◽

Vol 44 ◽

pp. 334-335

Author(s):

Veronika Burmeister ◽

R. Swaminathan

Keyword(s):

Electron Microscopy ◽

Transmission Electron Microscopy ◽

Basement Membrane ◽

Middle Age ◽

Porphyria Cutanea Tarda ◽

Minor Trauma ◽

Electron Microscopic ◽

Transmission Electron Microscopic Study ◽

Transmission Electron ◽

Transmission Electron Microscopic

Porphyria cutanea tarda (PCT) is a disorder of porphyrin metabolism which occurs most often during middle age. The disease is characterized by excessive production of uroporphyrin which causes photosensitivity and skin eruptions on hands and arms, due to minor trauma and exposure to sunlight. The pathology of the blister is well known, being subepidermal with epidermodermal separation, it is not always absolutely clear, whether the basal lamina is attached to the epidermis or the dermis. The purpose of our investigation was to study the attachment of the basement membrane in the blister by comparing scanning with transmission electron microscopy.

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Several frailty parameters highly prevalent in middle age (50–65) are independent predictors of adverse events

Scientific Reports ◽

10.1038/s41598-021-88410-5 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Lauriane Segaux ◽

Amaury Broussier ◽

Nadia Oubaya ◽

Claire Leissing-Desprez ◽

Marie Laurent ◽

...

Keyword(s):

Adverse Events ◽

Middle Age ◽

Executive Dysfunction ◽

Community Dwelling ◽

Living Alone ◽

Middle Aged ◽

Cross Sectional ◽

Balance Impairment ◽

Logistic Regression Models ◽

Paris Area

AbstractAlthough frailty can arise in middle age, very few studies have investigated frailty before 65 years. Our objectives were to assess the prevalence of frailty parameters in middle-aged individuals and probe the association with future adverse events. We performed cross-sectional and longitudinal analyses of community-dwelling individuals aged 50 to 65 (n = 411, median age: 59.0) having undergone a multidomain geriatric assessment (2010–2015) in an outpatient clinic in the greater Paris area of France (SUCCEED cohort). The primary outcome was a composite measure of adverse events (non-accidental falls, fractures, unplanned hospitalizations, death), recorded in 2016/2017. Multivariable logistic regression models were built to identify independent predictors. Six frailty parameters were highly prevalent (> 20%): low activity (40.1%), exhaustion (31.3%), living alone (28.5%), balance impairment (26.8%), weakness (26.7%), and executive dysfunction (23.2%). Female sex (odds ratio: 2.67 [95% confidence interval: 1.17–6.11]), living alone (2.39 [1.32–4.33]), balance impairment (2.09 [1.16–3.78]), executive dysfunction (2.61, [1.18–5.77]), and exhaustion (2.98 [1.65–5.39]) were independent predictors of adverse events. Many frailty parameters are already altered in middle-aged individuals and are predictive of adverse health events. Our findings highlight a possible need for frailty screening and preventive programs targeting middle-aged individuals.

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Low-dose aspirin prevents age-related endothelial dysfunction in a mouse model of physiological aging

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00241.2007 ◽

2008 ◽

Vol 294 (4) ◽

pp. H1562-H1570 ◽

Cited By ~ 37

Author(s):

Hélène Bulckaen ◽

Gaétan Prévost ◽

Eric Boulanger ◽

Géraldine Robitaille ◽

Valérie Roquet ◽

...

Keyword(s):

Oxidative Stress ◽

Endothelial Dysfunction ◽

Protective Effect ◽

Structural Changes ◽

Low Dose ◽

Age Groups ◽

Dose Aspirin ◽

Age Related ◽

Low Dose Aspirin ◽

Old Mice

The age-related impairment of endothelium-dependent vasodilatation contributes to increased cardiovascular risk in the elderly. For primary and secondary prevention, aspirin can reduce the incidence of cardiovascular events in this patient population. The present work evaluated the effect of low-dose aspirin on age-related endothelial dysfunction in C57B/J6 aging mice and investigated its protective antioxidative effect. Age-related endothelial dysfunction was assessed by the response to acetylcholine of phenylephrine-induced precontracted aortic segments isolated from 12-, 36-, 60-, and 84-wk-old mice. The effect of low-dose aspirin was examined in mice presenting a decrease in endothelial-dependent relaxation (EDR). The effects of age and aspirin treatment on structural changes were determined in mouse aortic sections. The effect of aspirin on the oxidative stress markers malondialdehyde and 8-hydroxy-2′-deoxyguanosine (8-OhdG) was also quantified. Compared with that of 12-wk-old mice, the EDR was significantly reduced in 60- and 84-wk-old mice ( P < 0.05); 68-wk-old mice treated with aspirin displayed a higher EDR compared with control mice of the same age (83.9 ± 4 vs. 66.3 ± 5%; P < 0.05). Aspirin treatment decreased 8-OHdG levels ( P < 0.05), but no significant effect on intima/media thickness ratio was observed. The protective effect of aspirin was not observed when treatment was initiated in older mice (96 wk of age). It was found that low-dose aspirin is able to prevent age-related endothelial dysfunction in aging mice. However, the absence of this effect in the older age groups demonstrates that treatment should be initiated early on. The underlying mechanism may involve the protective effect of aspirin against oxidative stress.

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Rapamycin reverses age-related increases in mitochondrial ROS production at complex I, oxidative stress, accumulation of mtDNA fragments inside nuclear DNA, and lipofuscin level, and increases autophagy, in the liver of middle-aged mice

Experimental Gerontology ◽

10.1016/j.exger.2016.08.002 ◽

2016 ◽

Vol 83 ◽

pp. 130-138 ◽

Cited By ~ 39

Author(s):

V. Martínez-Cisuelo ◽

J. Gómez ◽

I. García-Junceda ◽

A. Naudí ◽

R. Cabré ◽

...

Keyword(s):

Oxidative Stress ◽

Complex I ◽

Nuclear Dna ◽

Ros Production ◽

Middle Aged ◽

Aged Mice ◽

Age Related ◽

Mitochondrial Ros ◽

Stress Accumulation

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Sleep apnoea and visceral adiposity in middle-aged male and female subjects

European Respiratory Journal ◽

10.1183/09031936.00183411 ◽

2012 ◽

Vol 41 (3) ◽

pp. 601-609 ◽

Cited By ~ 60

Author(s):

Ilia Kritikou ◽

Maria Basta ◽

Rafel Tappouni ◽

Slobodanha Pejovic ◽

Julio Fernandez-Mendoza ◽

...

Keyword(s):

Sleep Apnoea ◽

Visceral Adiposity ◽

Middle Aged ◽

Male And Female ◽

Middle Aged Male ◽

Female Subjects

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Abstract P748: Transcriptome Profiling of the Neural Stem Cell Niche and the Effect of Exercise in Restoring Neurogenesis in Type II Diabetic Mice

Stroke ◽

10.1161/str.52.suppl_1.p748 ◽

2021 ◽

Vol 52 (Suppl_1) ◽

Author(s):

Gratianne Rabiller ◽

Atsushi Kanoke ◽

Jialing Liu

Keyword(s):

Oxidative Stress ◽

Deleterious Effect ◽

Wheel Running ◽

Enrichment Analysis ◽

Transcriptome Profiling ◽

Cell Types ◽

Neural Regeneration ◽

Diabetic Mice ◽

Middle Aged ◽

Neurogenic Niche

Introduction: Previously we found that mice with type 2 diabetes (T2DM) exhibited an accelerated age-associated decline in neurogenesis during baseline and after ischemic stroke compared to age-matched control mice. The current study sought to delineate the transcriptome landscape involved in the impaired neurogenesis and determine if exercise can prevent the deleterious effect of T2DM on neural regeneration. Hypothesis: We hypothesize that T2DM alters signaling pathways regulating neurogenesis and daily exercise mitigates the deleterious effect on neurogenesis in the T2DM mice. Methods: Transcriptome profiling was performed by single cell RNA sequencing (scRNAseq) of SVZ and DG cells in stroke and non-stroke mice using the 10X Genomics platform. T2DM-induced differential gene expression was analyzed by ClusterProfiler and Wikipathways enrichment analysis. Middle-aged (~260 days old) and old (~700 days old) db/+ or db/db mice were subjected to daily wheel-running exercise for one month. BrdU at 50 mg/kg twice daily for 2 consecutive days was injected i.p. at the end of the experiment to track proliferating neuroprogenitor cells. DCX+ cells and BrDU+ cells were quantified in the dentate gyrus of the hippocampus. Results: The scRNAseq analysis revealed multiple cell types co-existing in the neurogenic niche. GO and Wikipathways enrichment analysis showed that under diabetic condition, genes such as Qdpr, Hsp90ab1, Hsp90aa1, and Sox9 were downregulated in pathways involving eNOS activation; whereas Junb, C1qc, C1qb and C1qa were upregulated in the pathways related to oxidative stress. Exercise, known to increase eNOS expression and reduce oxidative stress-induced cell death, significantly restored the number of DCX+ immature neurons in 8-months-old diabetic mice almost to the level of the control mice without exercise Conclusions: Exercise restores neurogenesis by increasing the number of neuroblasts in the middle-aged diabetic mice. Ongoing experiment will investigate whether exercise promotes neurogenesis by enhancing eNOS and improved blood flow, and inducing genes involved in the survival of the NSC niche of the diabetic mice.

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Staying ‘stoked’: Surfing, ageing and post-youth identities

International Review for the Sociology of Sport ◽

10.1177/1012690217722522 ◽

2017 ◽

Vol 54 (4) ◽

pp. 387-409 ◽

Cited By ~ 5

Author(s):

Belinda Wheaton

Keyword(s):

Middle Age ◽

Cultural Barriers ◽

Physically Active ◽

Men And Women ◽

Male And Female ◽

South West ◽

Barriers And Challenges ◽

Ways Of Being ◽

Scholarly Attention ◽

Equipment Performance

Surfing has consistently been framed as a youth focused, male-dominated sport and culture. Despite surfing’s ageing demographic, neither the ways in which age impacts on surfing identities and mobilities, nor older surfer’s experiences and subjectivities, has been given scholarly attention. In this paper, I discuss research exploring the experiences and identities of middle-aged and older recreational male and female surfers in the south and south-west of England. The research illustrates that participation in surfing as a sport and lifestyle remains highly significant for some men and women through middle-age and into retirement. I consider the cultural barriers and challenges in dealing with a loss in physical performance through ageing, such as adaptations to their equipment, performance, and style, and the implications for how individuals negotiate bodily capital, space and identity. Nonetheless, older surfers also embrace different ways of being a surfer which challenge some of the more exclusionary aspects of surfing identities. Theoretically the paper develops an intersectional approach to sporting identity that explicitly recognises and accounts for the contribution of age to social identity. The research also contributes to the growing literature on physically active ‘post-youth’ leisure lifestyles, illustrating how shifting definitions of ageing have given ‘rise to new expectations, priorities and understandings’ of sporting lifestyles amongst those in middle age, and beyond.

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