scholarly journals Site-specific gains and losses of heterochromatin accelerate the age-related neurodegeneration through the cascading destruction of KDM3B-centered epigenomic network

2022 ◽  
Author(s):  
Mi-Jin An ◽  
Ji-Young Kim ◽  
Jinhong Park ◽  
Jinho Kim ◽  
Dae-Hyun Kim ◽  
...  
Keyword(s):  
Transcriptome Profiling ◽  
Mouse Retina ◽  
Sequencing Analysis ◽  
Epigenetic Alterations ◽  
Ribbon Synapses ◽  
Age Related ◽  
Retinal Neurodegeneration ◽  
Apoptotic Genes ◽  
Gains And Losses ◽  
Universal Mechanism

Abstract Epigenetic alterations explained by the “loss of heterochromatin” model have been proposed as a universal mechanism of aging, but the region-specific changes of heterochromatin during aging are unclear. Here, we examine age-dependent transcriptomic profiling of mouse retinal neurons to identify epigenetic regulators involved in heterochromatin loss. RNA sequencing analysis revealed gradual down-regulation of Kdm3b during retinal aging. Disruption of Kdm3b (Kdm3b+/-) in 12-month-old mouse retina decreased the number of cone photoreceptors and changed the morphology of cone ribbon synapses. Integration of transcriptome profiling with epigenomic analysis demonstrated gain of heterochromatin feature in synapse assembly and vesicle transport genes via the accumulation of H3K9 mono- and di-methylation. However, the loss of heterochromatin in apoptotic genes exacerbated retinal neurodegeneration. We propose that this KDM3B-centered epigenomic network is crucial for maintaining cone photoreceptor homeostasis via the modulation of gene-set specific heterochromatin features during aging.

scholarly journals The TOMM40 ‘523’ polymorphism in disease risk and age of symptom onset in two independent cohorts of Parkinson’s disease

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Megan C. Bakeberg ◽  
Madison E. Hoes ◽  
Anastazja M. Gorecki ◽  
Frances Theunissen ◽  
Abigail L. Pfaff ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Symptom Onset ◽  
Disease Risk ◽  
Age Of Onset ◽  
Sequencing Analysis ◽  
Age Related ◽  
Australian Cohort ◽  
Progression Markers ◽  
Age Related Cognitive Decline

AbstractAbnormal mitochondrial function is a key process in the pathogenesis of Parkinson’s disease (PD). The central pore-forming protein TOM40 of the mitochondria is encoded by the translocase of outer mitochondrial membrane 40 homologue gene (TOMM40). The highly variant ‘523’ poly-T repeat is associated with age-related cognitive decline and age of onset in Alzheimer’s disease, but whether it plays a role in modifying the risk or clinical course of PD it yet to be elucidated. The TOMM40 ‘523’ allele length was determined in 634 people with PD and 422 healthy controls from an Australian cohort and the Parkinson’s Progression Markers Initiative (PPMI) cohort, using polymerase chain reaction or whole genome sequencing analysis. Genotype and allele frequencies of TOMM40 ‘523’ and APOE ε did not differ significantly between the cohorts. Analyses revealed TOMM40 ‘523’ allele groups were not associated with disease risk, while considering APOE ε genotype. Regression analyses revealed the TOMM40 S/S genotype was associated with a significantly later age of symptom onset in the PPMI PD cohort, but not after correction for covariates, or in the Australian cohort. Whilst variation in the TOMM40 ‘523’ polymorphism was not associated with PD risk, the possibility that it may be a modifying factor for age of symptom onset warrants further investigation in other PD populations.

scholarly journals Exacerbation of AMD Phenotype in Lasered CNV Murine Model by Dysbiotic Oral Pathogens

Antioxidants ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 309
Author(s):  
Pachiappan Arjunan ◽  
Radhika Swaminathan ◽  
Jessie Yuan ◽  
Mohamed Elashiry ◽  
Amany Tawfik ◽  
...  
Keyword(s):  
Murine Model ◽  
Retinal Thickness ◽  
Age Related Macular Degeneration ◽  
Periodontal Pathogen ◽  
Fundus Photography ◽  
Mouse Retina ◽  
Rrna Gene ◽  
Age Related ◽  
Periodontal Infection

Emerging evidence underscores an association between age-related macular degeneration (AMD) and periodontal disease (PD), yet the biological basis of this linkage and the specific role of oral dysbiosis caused by PD in AMD pathophysiology remains unclear. Furthermore, a simple reproducible model that emulates characteristics of both AMD and PD has been lacking. Hence, we established a novel AMD+PD murine model to decipher the potential role of oral infection (ligature-enhanced) with the keystone periodontal pathogen Porphyromonas gingivalis, in the progression of neovasculogenesis in a laser-induced choroidal-neovascularization (Li-CNV) mouse retina. By a combination of fundus photography, optical coherence tomography, and fluorescein angiography, we documented inflammatory drusen-like lesions, reduced retinal thickness, and increased vascular leakage in AMD+PD mice retinae. H&E further confirmed a significant reduction of retinal thickness and subretinal drusen-like deposits. Immunofluorescence microscopy revealed significant induction of choroidal/retinal vasculogenesis in AMD+PD mice. qPCR identified increased expression of oxidative-stress, angiogenesis, pro-inflammatory mediators, whereas antioxidants and anti-inflammatory genes in AMD+PD mice retinae were notably decreased. Through qPCR, we detected Pg and its fimbrial 16s-RrNA gene expression in the AMD+PD mice retinae. To sum-up, this is the first in vivo study signifying a role of periodontal infection in augmentation of AMD phenotype, with the aid of a pioneering AMD+PD murine model established in our laboratory.

scholarly journals Formaldehyde and De/Methylation in Age-Related Cognitive Impairment

Genes ◽  
2021 ◽  
Vol 12 (6) ◽  
pp. 913
Author(s):  
Ting Li ◽  
Yan Wei ◽  
Meihua Qu ◽  
Lixian Mou ◽  
Junye Miao ◽  
...  
Keyword(s):  
Amino Acids ◽  
Cell Proliferation ◽  
Cognitive Impairment ◽  
Metabolic Pathways ◽  
Memory Formation ◽  
Epigenetic Alterations ◽  
Diagnostic Biomarker ◽  
Reactive Substance ◽  
Age Related ◽  
Novel Therapeutic

Formaldehyde (FA) is a highly reactive substance that is ubiquitous in the environment and is usually considered as a pollutant. In the human body, FA is a product of various metabolic pathways and participates in one-carbon cycle, which provides carbon for the synthesis and modification of bio-compounds, such as DNA, RNA, and amino acids. Endogenous FA plays a role in epigenetic regulation, especially in the methylation and demethylation of DNA, histones, and RNA. Recently, epigenetic alterations associated with FA dysmetabolism have been considered as one of the important features in age-related cognitive impairment (ARCI), suggesting the potential of using FA as a diagnostic biomarker of ARCI. Notably, FA plays multifaceted roles, and, at certain concentrations, it promotes cell proliferation, enhances memory formation, and elongates life span, effects that could also be involved in the aetiology of ARCI. Further investigation of and the regulation of the epigenetics landscape may provide new insights about the aetiology of ARCI and provide novel therapeutic targets.

scholarly journals Comparative Transcriptome Profiling Reveals Defense-Related Genes against Meloidogyne incognita Invasion in Tobacco

Molecules ◽  
2018 ◽  
Vol 23 (8) ◽  
pp. 2081 ◽  
Author(s):  
Xiaohui Li ◽  
Xuexia Xing ◽  
Pei Tian ◽  
Mingzhen Zhang ◽  
Zhaoguang Huo ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Meloidogyne Incognita ◽  
Resistance Mechanism ◽  
Transcriptome Profiling ◽  
Ethylene Response Factor ◽  
Sequencing Analysis ◽  
Cell Wall Modification ◽  
Resistance Response ◽  
Helix Loop Helix ◽  
Genes Encoding

Root-knot nematodes Meloidogyne incognita are one of the most destructive pathogens, causing severe losses to tobacco productivity and quality. However, the underlying resistance mechanism of tobacco to M. incognita is not clear. In this study, two tobacco genotypes, K326 and Changbohuang, which are resistant and susceptible to M. incognita, respectively, were used for RNA-sequencing analysis. An average of 35 million clean reads were obtained. Compared with their expression levels in non-infected plants of the same genotype, 4354 and 545 differentially expressed genes (DEGs) were detected in the resistant and susceptible genotype, respectively, after M. incognita invasion. Overall, 291 DEGs, involved in diverse biological processes, were common between the two genotypes. Genes encoding toxic compound synthesis, cell wall modification, reactive oxygen species and the oxidative burst, salicylic acid signal transduction, and production of some other metabolites were putatively associated with tobacco resistance to M. incognita. In particular, the complex resistance response needed to overcome M. incognita invasion may be regulated by several transcription factors, such as the ethylene response factor, MYB, basic helix–loop–helix transcription factor, and indole acetic acid–leucine-resistant transcription factor. These results may aid in the identification of potential genes of resistance to M. incognita for tobacco cultivar improvement.

Subjective perceptions of age-related gains buffer negative associations of perceived age-related losses with health, well-being, and engagement

2021 ◽  
pp. 016502542110390
Author(s):  
Tim D. Windsor ◽  
Mandy J. Abbott ◽  
Monica Cations ◽  
Alexis J. Howard ◽  
Bethany Wilton-Harding
Keyword(s):  
Physical Functioning ◽  
Leisure Activities ◽  
Developmental Outcomes ◽  
Well Being ◽  
Subjective Well Being ◽  
Crowd Sourcing ◽  
Online Questionnaire ◽  
Sense Of Purpose ◽  
Age Related ◽  
Gains And Losses

People reflect on their own aging, and this subjective awareness has an influence on developmental outcomes. Scholars have recently operationalized subjective aging in terms of awareness of age-related change (AARC), which captures awareness of both gains and losses. We examined associations of AARC-gains and AARC-losses with physical functioning, subjective well-being, and engagement with life (enjoyable activities and sense of purpose). Importantly, we extended previous research by not only assessing main effects of gains and losses but also testing their interaction. We hypothesized that awareness of losses would be more weakly negatively associated with health and well-being among those who possessed higher awareness of gains. A total of 399 older participants aged 65 to 91 (235 women and 164 men) were recruited via Prime Panels crowd-sourcing platform to complete an online questionnaire. Greater AARC-losses was associated with poorer health, lower subjective well-being, and lower sense of purpose. AARC-gains was associated with better outcomes in general, and moderated associations of AARC-losses with physical functioning, subjective well-being, and sense of purpose (but not engagement in leisure activities). Consistent with predictions, moderation effects showed that negative associations of AARC-losses with the outcomes were weaker among those who reported higher AARC-gains. Results provided some support for a role of AARC-gains in buffering negative effects of AARC-losses on developmental outcomes.

Transcriptome Profile of Hippocampus in Rats Model of Acute Myocardial Ischemia in Response to Electroacupuncture

2020 ◽  
Author(s):  
Xin Wu ◽  
Chenkai Wang ◽  
Kun Wang ◽  
Shuai Cui ◽  
Shengbing Wu ◽  
...  
Keyword(s):  
Myocardial Ischemia ◽  
Transcriptome Profiling ◽  
Arachidonic Acid Metabolism ◽  
Acute Myocardial Ischemia ◽  
Sequencing Analysis ◽  
Beneficial Effects ◽  
Positive Effects ◽  
Gabaergic Synapses ◽  
The Brain ◽  
Gene Expression Levels

Abstract Background: Electroacupuncture (EA) alleviates acute myocardial ischemia (AMI) by regulating some brain areas, including hippocampus. The locus coeruleus (LC) is the main source of norepinephrine (NE) in the brain, including the hippocampus, and regulates cardiovascular function. The aim of the present work was to assess whether LC mediates the positive effects of EA in AMI by altering gene expression levels in the hippocampus. We addressed this in the present study by hippocampus transcriptome profiling in a rat model of AMI following EA treatment. Results: Myocardial injury markers (ischemia-modified albumin, homocysteine and lipoprotein- associated phospholipase A2) in the serum were downregulated in EA (P<0.05) compared to the M group and upregulated in E+L group (P<0.05) compared to E group. RNA sequencing analysis of the hippocampus revealed that the downregulation of 27 genes in M vs S as well as upregulation of 40 genes in M vs S were reversed by EA. These differentially expressed genes, which were validated by quantitative real-time PCR, were enriched in 20 Kyoto Encyclopedia of Genes and Genomes pathways related to glycerolipid, glycerophospholipid, and arachidonic acid metabolism as well asnervous system function (glutamatergic, cholinergic, serotonergic, GABAergic synapses). Conclusions: LC mediates the beneficial effects of EA on AMI-induced injury may be related to the observed transcriptional regulations in the hippocampus. These results provide molecular-level evidence for the therapeutic efficacy of EA in the treatment of AMI.

Age-related insult of cochlear ribbon synapses: An early-onset contributor to D-galactose-induced aging in mice

2020 ◽  
Vol 133 ◽  
pp. 104649 ◽  
Author(s):  
Zheng-De Du ◽  
Shu-Guang Han ◽  
Teng-Fei Qu ◽  
Bin Guo ◽  
Shu-Kui Yu ◽  
...  
Keyword(s):  
Early Onset ◽  
Ribbon Synapses ◽  
Age Related

Managing expectations: How stress, social support, and aging attitudes affect awareness of age-related changes

2019 ◽  
Vol 37 (3) ◽  
pp. 986-1007
Author(s):  
Erica L. O’Brien ◽  
Neika Sharifian
Keyword(s):  
Social Support ◽  
Online Survey ◽  
Well Being ◽  
Age Related ◽  
Aging Attitudes ◽  
Amazon's Mechanical Turk ◽  
And Function ◽  
Gains And Losses ◽  
Future Work ◽  
Age Related Changes

The degree to which social support (SS) moderates the effects of stress on self-perceptions of aging may depend on individual differences in general aging attitudes. We examined how stress, different types of SS, and general expectations regarding aging (ERA) affect awareness of age-related changes (AARCs). The sample included 137 adults (21–76 years; 56.2% women) who took an online survey on Amazon’s Mechanical Turk. Regression analyses showed differential moderation of stress effects due to ERA and the SS measure (perceived and received) and function (emotional and instrumental). Received emotional SS was only associated with AARC losses, whereas perceived support—both emotional and instrumental—was associated with AARC gains and losses. Findings may help guide future work aimed at promoting health and well-being in adulthood.

scholarly journals Mid and hindgut transcriptome profiling analysis of Atlantic salmon ( Salmon salar ) under unpredictable chronic stress

2020 ◽  
Vol 7 (2) ◽  
pp. 191480
Author(s):  
Signe Dille Løvmo ◽  
Angelico Madaro ◽  
Paul Whatmore ◽  
Tora Bardal ◽  
Mari-Ann Ostensen ◽  
...  
Keyword(s):  
Atlantic Salmon ◽  
Chronic Stress ◽  
Transcriptome Profiling ◽  
Intestinal Morphology ◽  
Differentially Expressed ◽  
Sequencing Analysis ◽  
Negative Consequences ◽  
Membrane Structures ◽  
Apoptotic Pathway ◽  
Salmon Parr

The intestinal epithelium is a selectively permeable barrier for nutrients, electrolytes and water, while maintaining effective protection against pathogens. Combinations of stressors throughout an animal's life, especially in agriculture and aquaculture settings, may affect the regular operativity of this organ with negative consequences for animal welfare. In the current study, we report the effects of a three-week unpredictable chronic stress (UCS) period on the intestinal morphology and transcriptome response of Atlantic salmon ( Salmon salar ) parr midgut and hindgut. Midgut and hindgut from both control and UCS fish were collected for histology and RNA-sequencing analysis to identify respective changes in the membrane structures and putative genes and pathways responding to UCS. Histological analysis did not show any significant effect on morphometric parameters. In the midgut, 1030 genes were differentially expressed following UCS, resulting in 279 genes which were involved in 13 metabolic pathways, including tissue repair pathways. In the hindgut, following UCS, 591 differentially expressed genes were detected with 426 downregulated and 165 upregulated. A total of 53 genes were related to three pathways. Downregulated genes include cellular senescence pathways, p53 signalling and cytokine–cytokine receptor pathways. The overall results corroborate that salmon parr were at least partly habituating to the UCS treatment. In midgut, the main upregulation was related to cell growth and repair, while in the hindgut there were indications of the activated apoptotic pathway, reduced cell repair and inhibited immune/anti-inflammatory capacity. This may be the trade-off between habituating to UCS and health resilience. This study suggests possible integrated genetic regulatory mechanisms that are tuned when farmed Atlantic salmon parr attempt to cope with UCS.

scholarly journals The Expression of Decidual Protein Induced by Progesterone (DEPP) Is Controlled by Three Distal Consensus Hypoxia Responsive Element (HRE) in Hypoxic Retinal Epithelial Cells

Genes ◽  
2020 ◽  
Vol 11 (1) ◽  
pp. 111
Author(s):  
Katrin Klee ◽  
Federica Storti ◽  
Jordi Maggi ◽  
Vyara Todorova ◽  
Duygu Karademir ◽  
...  
Keyword(s):  
Cell Line ◽  
Pigment Epithelium ◽  
Transcriptional Start Site ◽  
Retinal Pigment ◽  
Genomic Region ◽  
Mouse Retina ◽  
Hypoxic Induction ◽  
Age Related ◽  
Responsive Element ◽  
Retinal Pathologies

Hypoxia affects the development and/or progression of several retinopathies. Decidual protein induced by progesterone (DEPP) has been identified as a hypoxia-responsive gene that may be part of cellular pathways such as autophagy and connected to retinal diseases. To increase our understanding of DEPP regulation in the eye, we defined its expression pattern in mouse and human retina and retinal pigment epithelium (RPE). Interestingly, DEPP expression was increased in an age-dependent way in the central human RPE. We showed that DEPP was regulated by hypoxia in the mouse retina and eyecup and that this regulation was controlled by hypoxia-inducible transcription factors 1 and 2 (HIF1 and HIF2). Furthermore, we identified three hypoxia response elements (HREs) about 3.5 kb proximal to the transcriptional start site that were responsible for hypoxic induction of DEPP in a human RPE cell line. Comparative genomics analysis suggested that one of the three HREs resides in a highly conserved genomic region. Collectively, we defined the molecular elements controlling hypoxic induction of DEPP in an RPE cell line, and provided evidence for an enrichment of DEPP in the aged RPE of human donors. This makes DEPP an interesting gene to study with respect to aging and age-related retinal pathologies.

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