Supplementation of selenium-enriched yeast attenuates age-dependent transcriptional changes of heart in mitochondrial DNA mutator mice

2014 ◽  
Vol 4 (3) ◽  
pp. 98 ◽  
Author(s):  
Rijin Xiao ◽  
Leya Spangler ◽  
Katie Routt ◽  
Zijian Lan ◽  
Carrie Johnson ◽  
...  
Keyword(s):  
Cardiac Fibrosis ◽  
System Development ◽  
Heart Diseases ◽  
Control Diet ◽  
Key Words Aging ◽  
Transcription Profiles ◽  
Developing Heart ◽  
Age Related ◽  
Age Dependent ◽  
Transcriptional Changes

Background: Age is a major risk factor in developing heart diseases and has been associated with profound transcriptional changes in mammalian tissues. Low tissue selenium has recently been linked to several age-related diseases, including cardiovascular disease. This study investigated the global effects of age and dietary supplementation of selenium on heart transcriptional profiles in POLG mutator mice.Methods: Heart transcription profiles from young (2-month-old) and old (13-month-old) animals fed either a control diet or a diet supplemented with 1.0 mg selenium from selenium-enriched yeast (SP)/kg diet were obtained and validated using microarray and real-time RT-PCR techniques.Results: Aging led to significant transcriptional changes, where the expression of 1942 genes in old animals was changed by a fold change larger than 2.0, when compared to young animals. Age-regulated genes are associated with cardiovascular system development, immune and inflammatory response, and cellular oxidative stress response. Multiple genes linked with cardiomyocyte apoptosis, hypertrophy, and cardiac fibrosis, such as Myh7, Lcn2, Spp1, and Serpine1, were significantly up-regulated in old animals. SP supplementation also caused significant transcriptional changes in the heart, especially in old mice where many age-dependent transcriptional changes were totally or partially reversed by SP. Upstream regulator analysis further indicated that genes for Foxo1 and Foxo3, two transcriptional regulators involved in the regulation of cardiac muscle remodeling, were significantly activated by SP, suggesting that Foxo-mediated transcriptional activities play important roles in the anti-aging properties of SP.Conclusions: Results of this study indicate that SP supplementation attenuated age-related transcriptional changes in the heart of old POLG mice, which implies a potential clinical application of dietary selenium in preventing decline of cardiac function in old animals.  Key words: Aging, heart, gene expression, selenium

Eplerenone Reverses Age-Dependent Cardiac Fibrosis Through Downregulating Osteopontin

2021 ◽  
Author(s):  
Mahshid Malakootian ◽  
Majid Maleki ◽  
Negar Mohammadian ◽  
Maedeh Arabian
Keyword(s):  
Cardiac Fibrosis ◽  
Cardiac Tissue ◽  
Expression Level ◽  
Aged Rats ◽  
Geriatric Population ◽  
Functional Changes ◽  
Young Rats ◽  
New Therapeutic Approaches ◽  
Age Related ◽  
Age Dependent

Abstract Background: The risk of cardiovascular disease dramatically increases with Ageing. Nowadays it is fully revealed that the fibrotic remodelling is the main cause of cardiac structural and functional changes related to the normal aging process, but the related signaling pathways and mechanisms are incompletely understood. Thus finding the new therapeutic approaches targeting cardiac fibrotic remodelling, may be necessary to develop preventive care in geriatric population against cardiovascular diseases. In this study, we evaluated the potential role of osteopontin (OPN) as novel mediators of age-dependent fibrotic pathways in heart as well as the effect of eplerenone on cardiac fibrosis reversal. Methods: Fischer-344 (F-344) rats has been used as three groups: young rats (2–3months old), aged rats (22-24 months old) without any treatment and aged rats treated with eplerenone (100 mg/kg/day) for 2 weeks. The expression level of OPN has been evaluated using real-time PCR and histological assessments were done to assess cardiac tissue fibrosis.Results: The expression level of OPN in aged rats was significantly higher than young rats and treatment with eplerenone significantly attenuated the level of OPN as well as cardiac fibrosis compare to untreated aged rats. Conclusion: Targeting cardiac fibroblast function with eplerenone could decrease expression of OPN marker and cause to reversal age-related cardiac fibrotic changes.

scholarly journals Zone-specific damage of the olfactory epithelium under protein restriction

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Ayinuer Tuerdi ◽  
Shu Kikuta ◽  
Makoto Kinoshita ◽  
Teru Kamogashira ◽  
Kenji Kondo ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Olfactory Epithelium ◽  
Control Diet ◽  
Intervention Strategy ◽  
Protein Restriction ◽  
Outer Hair Cells ◽  
Basal Cells ◽  
Cell Dynamics ◽  
Age Related ◽  
Positive Effect

AbstractOxidative stress causes tissue damage, affecting age-related pathologies. Protein restriction (PR) provides a powerful intervention strategy for reducing oxidative stress, which may have a positive effect on individual organs. However, it is unknown whether PR intervention influences the olfactory system. Here, we investigated how 10 months of PR could affect the cell dynamics of the olfactory epithelium (OE) in mice. We found that PR reduced age-related loss of outer hair cells in the cochlea, providing preventive effects against age-related hearing loss. In contrast, PR resulted in reduced mature olfactory sensory neurons (OSNs), increased proliferative basal cells, and increased apoptotic OSNs in zone 1 (the only area containing neurons expressing NQO1 [quinone dehydrogenase 1]) of the OE in comparison with animals given a control diet. Substantial oxidative stress occurred in NQO1-positive cells and induced apoptotic OSNs in zone 1. These results indicate that in contrast to the positive effect on the auditory system, PR induces oxidative stress and structurally and functionally negative effects on OSNs in zone 1, which is probably involved in the bioactivation of NQO1.

scholarly journals Polyphenol Supplementation Reverses Age-Related Changes in Microglial Signaling Cascades

2021 ◽  
Vol 22 (12) ◽  
pp. 6373
Author(s):  
Ahmad Jalloh ◽  
Antwoine Flowers ◽  
Charles Hudson ◽  
Dale Chaput ◽  
Jennifer Guergues ◽  
...  
Keyword(s):  
Protein Interactions ◽  
Control Diet ◽  
Bioinformatic Analysis ◽  
Diet Group ◽  
Differentially Expressed ◽  
Signaling Cascades ◽  
Complex Nature ◽  
Differentially Expressed Proteins ◽  
Ms Analysis ◽  
Age Related

Microglial activity in the aging neuroimmune system is a central player in aging-related dysfunction. Aging alters microglial function via shifts in protein signaling cascades. These shifts can propagate neurodegenerative pathology. Therapeutics require a multifaceted approach to understand and address the stochastic nature of this process. Polyphenols offer one such means of rectifying age-related decline. Our group used mass spectrometry (MS) analysis to explicate the complex nature of these aging microglial pathways. In our first experiment, we compared primary microglia isolated from young and aged rats and identified 197 significantly differentially expressed proteins between these groups. Then, we performed bioinformatic analysis to explore differences in canonical signaling cascades related to microglial homeostasis and function with age. In a second experiment, we investigated changes to these pathways in aged animals after 30-day dietary supplementation with NT-020, which is a blend of polyphenols. We identified 144 differentially expressed proteins between the NT-020 group and the control diet group via MS analysis. Bioinformatic analysis predicted an NT-020 driven reversal in the upregulation of age-related canonical pathways that control inflammation, cellular metabolism, and proteostasis. Our results highlight salient aspects of microglial aging at the level of protein interactions and demonstrate a potential role of polyphenols as therapeutics for age-associated dysfunction.

scholarly journals The serotonin transporter gene and female personality variation in a free-living passerine

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Bert Thys ◽  
Andrea S. Grunst ◽  
Nicky Staes ◽  
Rianne Pinxten ◽  
Marcel Eens ◽  
...  
Keyword(s):  
Serotonin Transporter ◽  
Strong Support ◽  
Serotonin Transporter Gene ◽  
Female Aggression ◽  
Nucleotide Polymorphisms ◽  
Transporter Gene ◽  
Evolutionary Potential ◽  
Free Living ◽  
Age Related ◽  
Age Dependent

AbstractQuantifying variation in behaviour-related genes provides insight into the evolutionary potential of repeatable among-individual variation in behaviour (i.e. personality). Yet, individuals typically also plastically adjust their behaviour in response to environmental conditions and/or age, thereby complicating the detection of genotype–phenotype associations. Here, using a population of free-living great tits (Parus major), we assessed the association between single nucleotide polymorphisms (SNPs) in the serotonin transporter gene (SERT) and two repeatable behavioural traits, i.e. female-female aggression and female hissing behaviour. For female-female aggression, a trait showing age-related plasticity, we found no evidence for associations with SERT SNPs, even when assessing potential age-dependent effects of SERT genotype on aggression. We also found no strong support for associations between SERT SNPs and hissing behaviour, yet we identified two synonymous polymorphisms (exon 13 SNP66 and exon 12 SNP144) of particular interest, each explaining about 1.3% of the total variation in hissing behaviour. Overall, our results contribute to the general understanding of the biological underpinning of complex behavioural traits and will facilitate further (meta-analytic) research on behaviour-related genes. Moreover, we emphasize that future molecular genetic studies should consider age-dependent genotype–phenotype associations for behavioural trait (co)variation, as this will vastly improve our understanding of the proximate causes and ultimate consequences of personality variation in natural populations.

scholarly journals Random errors in protein synthesis activate an age-dependent program of muscle atrophy in mice

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
James Moore ◽  
Rashid Akbergenov ◽  
Martina Nigri ◽  
Patricia Isnard-Petit ◽  
Amandine Grimm ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Muscle Atrophy ◽  
Strength Analysis ◽  
Dependent Manner ◽  
Random Errors ◽  
Age Related ◽  
Related Phenotype ◽  
Age Dependent ◽  
Translation Accuracy ◽  
Transcriptomic Changes

AbstractRandom errors in protein synthesis are prevalent and ubiquitous, yet their effect on organismal health has remained enigmatic for over five decades. Here, we studied whether mice carrying the ribosomal ambiguity (ram) mutation Rps2-A226Y, recently shown to increase the inborn error rate of mammalian translation, if at all viable, present any specific, possibly aging-related, phenotype. We introduced Rps2-A226Y using a Cre/loxP strategy. Resulting transgenic mice were mosaic and showed a muscle-related phenotype with reduced grip strength. Analysis of gene expression in skeletal muscle using RNA-Seq revealed transcriptomic changes occurring in an age-dependent manner, involving an interplay of PGC1α, FOXO3, mTOR, and glucocorticoids as key signaling pathways, and finally resulting in activation of a muscle atrophy program. Our results highlight the relevance of translation accuracy, and show how disturbances thereof may contribute to age-related pathologies.

scholarly journals Up-Regulating Relaxin Expression by G-Quadruplex Interactive Ligand to Achieve Antifibrotic Action

Endocrinology ◽  
2012 ◽  
Vol 153 (8) ◽  
pp. 3692-3700 ◽  
Author(s):  
Hui-Ping Gu ◽  
Sen Lin ◽  
Ming Xu ◽  
Hai-Yi Yu ◽  
Xiao-Jun Du ◽  
...  
Keyword(s):  
Rna Polymerase Ii ◽  
Cardiac Fibrosis ◽  
Cardiac Fibroblasts ◽  
Heart Diseases ◽  
Gene Promoter ◽  
Binding Motif ◽  
Endogenous Expression ◽  
G Quadruplex

Myocardial fibrosis is a key pathological change in a variety of heart diseases contributing to the development of heart failure, arrhythmias, and sudden death. Recent studies have shown that relaxin prevents and reverses cardiac fibrosis. Endogenous expression of relaxin was elevated in the setting of heart disease; the extent of such up-regulation, however, is insufficient to exert compensatory actions, and the mechanism regulating relaxin expression is poorly defined. In the rat relaxin-1 (RLN1, Chr1) gene promoter region we found presence of repeated guanine (G)-rich sequences, which allowed formation and stabilization of G-quadruplexes with the addition of a G-quadruplex interactive ligand berberine. The G-rich sequences and the G-quadruplexes were localized adjacent to the binding motif of signal transducer and activator of transcription (STAT)3, which negatively regulates relaxin expression. Thus, we hypothesized that the formation and stabilization of G-quadruplexes by berberine could influence relaxin expression. We found that berberine-induced formation of G-quadruplexes did increase relaxin gene expression measured at mRNA and protein levels. Formation of G-quadruplexes significantly reduced STAT3 binding to the promoter of relaxin gene. This was associated with consequent increase in the binding of RNA polymerase II and STAT5a to relaxin gene promoter. In cardiac fibroblasts and rats treated with angiotensin II, berberine was found to suppress fibroblast activation, collagen synthesis, and extent of cardiac fibrosis through up-regulating relaxin. The antifibrotic action of berberine in vitro and in vivo was similar to that by exogenous relaxin. Our findings document a novel therapeutic strategy for fibrosis through up-regulating expression of endogenous relaxin.

Diagnostic value of assessment of coronary calcification in dysplastic heart

2021 ◽  
Vol 19 (1) ◽  
pp. 75-77
Author(s):  
L. T. Pimenov ◽  
◽  
V. V. Remnyakov ◽  
M. Yu. Smetanin ◽  
E. N. Avdeev ◽  
...  
Keyword(s):  
Connective Tissue ◽  
System Development ◽  
Heart Diseases ◽  
Coronary Calcification ◽  
Diagnostic Value ◽  
Conduction Disorders ◽  
Increased Risk ◽  
Structural Heart Diseases ◽  
Connective Tissue Dysplasia ◽  
Functional Features

The problem of heart connective tissue dysplasia syndrome is extremely relevant due to the increased risk of rhythm and conduction disorders, infectious endocarditis, thromboembolism and sudden cardiac death (SCD). Structural heart diseases (SHD) are manifestations of minor anomalies of the cardiovascular system development. Dysplastic heart refers to the combination of constitutional, topographical, anatomical, and functional features of the heart in a patient with connective tissue dysplasia (CTD). The standard for the diagnosis of coronary calcification (CC), one of the known predictors of coronary heart disease (CHD) and complications of cardiovascular diseases (CVD), is multispiral computed tomography (MSCT).

Abstract 3426: Myostatin Deletion Preserves Cardiac Function in Senescent Mice

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Michael R Morissette ◽  
Janelle C Stricker ◽  
Anthony Rosenzweig
Keyword(s):  
Cardiac Function ◽  
Rhode Island ◽  
Cardiac Fibrosis ◽  
Physiological Role ◽  
Heart Association ◽  
Negative Regulator ◽  
Heart Weight ◽  
Cardiomyocyte Hypertrophy ◽  
Mrna Levels ◽  
Age Related

Myostatin (MSTN) is a well-known negative regulator of skeletal muscle mass, and MSTN inhibition is being considered as therapy for multiple conditions associated with muscle wasting, including sarcopenia of aging. We have previously shown that MSTN inhibits phenylephrine-induced cardiomyocyte hypertrophy, however whether MSTN has a physiological role in regulating cardiac hypertrophy or function at baseline or with aging remains unclear. To determine if MSTN is dynamically regulated with aging, we performed QRT-PCR on hearts from male wild-type (WT) senescent mice (24 months old (mos)) and rats (32 mos). MSTN mRNA levels were increased in old versus young (4 mos) hearts (2.5- and 4-fold respectively, p<0.05). To study the functional significance of MSTN in aging, we maintained germline MSTN-knockout mice (MSTN −/− ) and their WT littermates for 24 –27 months. We found no difference in heart weight of aged male MSTN −/− compared to WT mice (162.5±17.0 (n=4) vs 153.2±4.2 (n=4) mg, p=0.51), which would argue against an inhibitory role for MSTN in age-related increases in cardiac mass. We also performed echocardiography on unanesthetized senescent MSTN −/− and WT mice. MSTN −/− mice had better fractional shortening (58.1±2.0 (n=7) vs 49.4±1.2 (n=8) %, p=0.002) and smaller LV end-diastolic diameter (3.41±0.19 vs 2.71±0.14 mm, p=0.012) compared to WT. The decreased cardiac function seen in aged WT mice was associated with increased cardiac fibrosis on Masson-Trichrome stained sections. Western blot analysis also demonstrated a 3.3-fold increase in phospholamban phosphorylation in MSTN −/− hearts (p<0.05), compared to WT, while no differences in SERCA2a or calsequestrin protein levels were seen. We conclude that MSTN increases in the heart with aging, and that genetic deletion of MSTN results in improved cardiac function without a difference in heart mass in senescent mice. Decreased cardiac fibrosis and increased inhibition (phosphorylation) of phospholamban likely contribute to the better cardiac function seen in senescent MSTN −/− mice. These results suggest that inhibiting MSTN for sarcopenia in the elderly may also benefit cardiac function and could represent a novel therapeutic approach for ameliorating cardiac dysfunction and/or fibrosis. This research has received full or partial funding support from the American Heart Association, AHA Founders Affiliate (Connecticut, Maine, Massachusetts, New Hampshire, New Jersey, New York, Rhode Island, Vermont).

HEAT SHOCK PROTEIN 90 (90) IN AGE-DEPENDENT CHANGES IN THE NUMBER OF FIBROBLASTS IN HUMAN SKIN

2020 ◽  
pp. 40-45
Author(s):  
А. Г. Гунин ◽  
Н. Н. Голубцова ◽  
Н. К. Корнилова
Keyword(s):  
Heat Shock ◽  
Heat Shock Protein ◽  
Heat Shock Protein 90 ◽  
Nuclear Antigen ◽  
Positive Staining ◽  
Proliferating Cells ◽  
Age Related ◽  
Age Dependent ◽  
Human Dermis ◽  
Hsp 90

Целью работы стало исследование содержания белка теплового шока 90 ( HSP 90) в фибробластах дермы человека от эмбрионального развития и до глубокой старости (от 20 нед беременности до 85 лет), а также определение значения HSP 90 для возрастных изменений численности фибробластов в дерме человека. HSP 90, ядерный антиген пролиферирующих клеток ( PCNA ) выявляли в срезах кожи непрямым иммуногистохимическим методом. Результаты показали, что в коже человека от 20 нед беременности до 20 лет доля фибробластов дермы с положительной окраской на HSP 90 остается постоянной. С 21 года до 60 лет наблюдают планомерное уменьшение доли фибробластов дермы, имеющих положительную окраску на HSP 90. У людей 61-85 лет происходит резкое увеличение доли фибробластов дермы с положительной окраской на HSP 90. Возрастные изменения содержания HSP 90 положительных фибробластов в дерме статистически не связаны с возрастным уменьшением общего количества и доли PCNA -положительных фибробластов в дерме. The aim of this work was to examine the content of heat shock protein 90 ( HSP 90) in fibroblasts of human dermis from the development until deep aging (from 20 weeks of pregnancy until 85 years old), and defining of a role of HSP 90 in age-dependent changes in the number of fibroblasts in the dermis. HSP 90, proliferating cells nuclear antigen ( PCNA ) were detected with indirect immunohistochemical technique. Results showed that a portion of fibroblasts with positive staining for HSP 90 in the dermis is not changed from 20 weeks of development to 20 years old. Percent of HSP 90 positive fibroblasts in dermis is decreased from 21 to 60 years old. From 61 year, the number of HSP 90 positive fibroblasts in dermis is increased. Age-related changes in the number of HSP 90 positive fibroblasts is not statistically associated with an age-related decrease in a total number and percent of PCNA positive fibroblasts the dermis.

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