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Aging is an important risk factor for several human diseases such as cancer, cardiovascular disease and neurodegenerative disorders, resulting from a combination of genetic and environmental factors (e.g., diet, smoking, obesity and stress), which, at molecular level, cause changes in gene expression underlying the decline of physiological function...
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It needs two TALEs to tango: Programmable receptors for the imaging‐based analysis of 5‐methylcytosine (5mC) in DNA sequences of single cells are reported. Staining of SATIII DNA with pairs of 5mC‐sensitive and 5mC‐insensitive transcription‐activator‐like effectors (TALEs) allows the analysis of 5mC at a target nucleotide position and its direct co...
Citations
... Aberrant epigenetic reprogramming-driven signaling in response to oxidative stress or aging is a major miscreant in the silencing of genes, leading to many aging-related pathobiology and disease states [1][2][3][4][5][6][7]. The control of gene expression in mammals by methylation of cytosine residues at CpG dinucleotides in the 5′flanking regions of genes are mostly enriched in CpG nucleotides, and are designated as CpG islands [8]. ...
... Aging or oxidative-driven abnormal DNA methylation has been shown to be involved in the development of many age-related pathobiology [5,17,18]. Studies have now dictated the role of DNA methylation in the dysregulation of the genes related to aging-pathobiology [6]. Intriguingly, both aging and oxidative stress possess common molecular denominators and are found to be the major culprits for several aging-related diseases [19,20]. ...
The physiological quantum of stress-inducible transcriptional protein, Lens Epithelium-Derived Growth Factor (LEDGF), is vital for the maintenance of cellular physiology. Erratic epigenetic reprogramming in response to oxidative stress or with advancing age is found to be a major cause in the gene silencing, leading to pathobiologies. Using aging human (h) eye lens/lens epithelial cells (LECs) coupled with redox-active Peroxiredoxin 6 ( Prdx6 )-deficient ( Prdx6 −/− ) mLECs as model systems, herein, we showed that in aging/oxidative stress, the human LEDGF gene was regulated by unique methylation patterns of CGs nucleotides within and around the Sp1 binding site(s) of CpG island of the LEDGF promoter (−170 to −27nts). The process caused the repression of LEDGF and its target, Hsp27, resulting in reactive oxygen species (ROS) amplification and cellular insults. This phenomenon was opposed to the unmethylated promoter in LECs. Clinically, we observed that the loss of LEDGF in the Prdx6 −/− mLECs or aging lenses/LECs, correlating with increased expression of DNMT1, DNMT3a, and DNMT3b along with the methyl CpG binding protein 2 (MeCP2). Upon oxidative stress, the expression of these molecules was increased with the dramatic reduction in LEDGF expression. While demethylating agent, 5-Aza deoxycytidine (5-AzaC) transposed the aberrant methylation status, and revived LEDGF and Hsp27 expression. Mechanistically, the chloramphenicol acetyltransferase (CAT) reporter gene driven by the LEDGF promoter (−170/ + 35) and ChIP assays uncovered that 5-AzaC acted on GC/Sp1 sites to release LEDGF transcription. The data argued, for the first time, that de novo methylation of CGs around and within Sp1 sites of the CpG island directly disrupted Sp1 activity, which ensued in LEDGF repression and its biological functions. The findings should improve our understanding of cellular insults-associated with aberrant DNMTs-mediated LEDGF’s activity, and can offer strategies for therapeutic intervention to halt aging/oxidative stress-induced abnormalities.
... The aging DNA methylome reveals environment-by-aging interactions, highlighting the impact of environmental factors on epigenetic aging and showing the intricate interplay between lifestyle choices and environmental factors in gene expression and aging (Bertucci, 2021). Moreover, the effects of these alterations extend to transcriptional and metabolic changes that impact lifespan and the development of age-related diseases (Pagiatakis, 2019). ...
The aging process is a complex and intricate phenomenon influenced by many biological, environmental, social, and psychological factors. Within this complicated web of influences, the hallmarks of aging interact in a sophisticated network, highlighting the nuanced nature of biological aging. By examining research findings across various physiological systems such as skin, adipose tissue, connective tissue, skeletal muscles, and facial tissues, we can better understand the cellular and molecular underpinnings of facial aging. Adopting an interdisciplinary approach and utilizing innovative methodologies can pave the way for groundbreaking discoveries in aging research. We can optimize the outcomes of aging-related interventions by incorporating a comprehensive and interconnected approach into patient assessments, treatment planning, preventive guidance, therapeutic applications, continuing education, and collaborative research efforts.
... The PTMs include methylation, demethylation, acetylation, ADPribosylation, phosphorylation, and SUMOylation, and these PTMs cause a change in the expression of transcriptional genes, cell signaling, and protein trafficking (Hyeon et al. 2021). Epigenetic mechanisms are affected by physiological, pathological stimuli, and environmental factors like diet, stress, physical activity, lifestyle changes, and smoking (Pagiatakis et al. 2021). These aforementioned factors have been implicated in the occurrence and progression of HD. ...
Huntington’s disease (HD) is an inherited, autosomal, neurodegenerative ailment that affects the striatum of the brain. Despite its debilitating effect on its patients, there is no proven cure for HD management as of yet. Neuroinflammation, excitotoxicity, and environmental factors have been reported to influence the regulation of gene expression by modifying epigenetic mechanisms. Aside focusing on the etiology, changes in epigenetic mechanisms have become a crucial factor influencing the interaction between HTT protein and epigenetically transcribed genes involved in neuroinflammation and HD. This review presents relevant literature on epigenetics with special emphasis on neuroinflammation and HD. It summarizes pertinent research on the role of neuroinflammation and post-translational modifications of chromatin, including DNA methylation, histone modification, and miRNAs. To achieve this about 1500 articles were reviewed via databases like PubMed, ScienceDirect, Google Scholar, and Web of Science. They were reduced to 534 using MeSH words like ‘epigenetics, neuroinflammation, and HD’ coupled with Boolean operators. Results indicated that major contributing factors to the development of HD such as mitochondrial dysfunction, excitotoxicity, neuroinflammation, and apoptosis are affected by epigenetic alterations. However, the association between neuroinflammation-altered epigenetics and the reported transcriptional changes in HD is unknown. Also, the link between epigenetically dysregulated genomic regions and specific DNA sequences suggests the likelihood that transcription factors, chromatin-remodeling proteins, and enzymes that affect gene expression are all disrupted simultaneously. Hence, therapies that target pathogenic pathways in HD, including neuroinflammation, transcriptional dysregulation, triplet instability, vesicle trafficking dysfunction, and protein degradation, need to be developed.
... Apoptosis, a highly orchestrated form of programmed cell death, is crucial for maintaining tissue homeostasis and eliminating aberrant cells from multicellular organisms. Dysregulation of apoptosis has been implicated in various diseases, including cancer and neurodegenerative disorders, highlighting the significance of understanding the mechanisms that govern this intricate process [4,5]. Hence, there is a budding curiosity in identifying natural compounds that can modulate apoptosis, offering potential therapeutic applications. ...
Colorectal cancer is known for its substantial impact on global morbidity and mortality, with higher prevalence in developed regions. This study delves into the potential treatment advantages of resveratrol (RSV) in addressing colorectal cancer. Apoptosis and gene expression associated with apoptotic factors were explored using Caco-2 cells, a pertinent model for colorectal adenocarcinoma. The effect of RSV on Caco-2 cell viability was investigated using MTT assay and neutral red uptake assay. The level of generated ROS was high in cells exposed to RSV. Likewise, the enzyme superoxide dismutase, responsible for converting ROS into hydrogen peroxide, was concurrently elevated. The effect of RSV on DNA damage was examined through the TUNEL assay. The gene expression analyses for pro-apoptotic elements were studied using qRT-PCR. Furthermore, the impact of RSV on the migration of Caco-2 cells was conducted through a wound-healing assay. Our results reveal RSV’s cytotoxicity on Caco-2 cells, showing dose-dependent inhibition of viability, indicating its promise as a treatment agent. The induction of cell death by apoptosis is substantiated by DNA damage. Notably, the upregulated expression of caspase-3, Bax, and p53 genes suggests RSV’s potential to modulate key apoptosis-related elements. In addition, RSV displayed an inhibitory effect on cellular migration, a significant (p < 0.05 and p < 0.01) in cancer metastasis. These findings underscore RSV’s potential to be a multifaceted therapeutic agent targeting apoptosis and metastatic processes in colorectal cancer.
... [1][2][3][4] This debilitation is the major cause of substantial age-related disorders, including cardiovascular diseases, cancer, neurodegenerative disease, and diabetes. 3,5 Nevertheless, aging has several common features, such as (i) impotent intercellular communication, (ii) impairment of proteostasis, (iii) mitochondrial disorder, (iv) genomic alteration, (v) epigenetic modifications, (vi) cellular senescence, (vii) nutrient-sensing misfunction, (viii) stem cell debility, and (ix) telomere shortening. 3,6 The present review, however, focuses on the regulatory role of mitochondria in the aging process. ...
Mitochondria are ATP-producing organelles in eukaryotic organisms that serve as the cell’s power plants. Besides, mitochondria are integral to regulating cellular homeostasis and metabolism as a result of their essential roles in reactive oxygen species (ROS) production, bioenergetics, catabolism and anabolism, heme and iron-sulfur biosynthesis, iron and calcium homeostasis, apoptosis and signal transduction, as well as immunity and inflammation. It is well accepted that mitochondria are evolutionarily derived from endosymbiotic alphaproteobacteria within eukaryotic cells adapted for effective energy transduction. Although most of the mitochondrial DNA (mtDNA) is thought to have been transported to the eukaryotic nucleus during evolution, mitochondria may have preserved protein-coding genes within their own DNA. Accumulating data show that a progressive decline of mitochondria regulates aging. The present review aims to outline the role of mitochondria in various aspects of aging, including unfolded protein response, generation of ROS, and the contribution of somatic mtDNA mutations as well as inflammation in aging. Moreover, we propose mitochondria-targeted nanoparticles and mitochondrial genome editing as novel tools to modify mitochondrial genome aberrations.
... Finally, the allostatic load also includes the physiological consequences of all these health-damaging behaviours, such as lack of sleep, lack of exercise, smoking, alcohol consumption and an unhealthy diet (Pagiatakis et al., 2021). Such unhealthy behaviours can further worsen the allostatic overload produced by life challenges that exceed the person's ability to cope with them. ...
Aim
Patients' death or adverse events appear to be associated with poor healthcare decision‐making. This might be due to an inability to have an adequate representation of the problem or of the connections among problem‐related elements. Changing how a problem is formulated can reduce biases in clinical reasoning. The purpose of this article is to explore the possible contributions of psychoneuroendocrinoimmunology (PNEI) and psychology of reasoning and decision‐making (PRDM) to support a new nursing theoretical frame.
Design
Discursive paper.
Method
This article discusses the main assumptions about nursing and nurses' ability to face patient's problems, suggesting a new approach that integrates knowledge from PNEI and PRDM. While PNEI explains the complexity of systems, highlighting the importance of systems connections in affecting health, PRDM underlines the importance of the informative context in creating a mental representation of the problem. Furthermore, PRDM suggests the need to pay attention to information that is not immediately explicit and its connections.
Conclusion
Nursing recognizes the patient–nurse relationship as the axiom that governs care. The integration of PNEI and PRDM in nursing theoretics allows the expansion of the axiom by providing essential elements to read a new type of relationship: the relationship among information. PNEI explains the relationships between biological systems and the psyche and between the whole individual and the environment; PRDM provides tools for the nurse's analytical thinking system to correctly process information and its connections.
Impact on Nursing Practice
A theoretical renewal is mandatory to improve nursing reasoning and nursing priority identification. Integrating PNEI and PRDM into nursing theoretics will modify the way professionals approach patients, reducing cognitive biases and medical errors.
No Patient or Public Contribution
There was no patient or public involvement in the design or writing of this discursive article.
... Epigenetic modifications are modulations in gene expression without DNA modifications [21]. This modulation can be done through DNA modifications, histone alterations, non-coding RNAs, or ATP-dependent chromatin remodeling complexes [22]. ...
... DNA methylation occurs because DNA-methyltransferase adds a methyl group to cytokines, generally in regions rich in guanine and cytosine. These regions are called "CpG islands" and are part of the non-coding DNA, but their importance lies in the fact that they are usually located in the promoter region of most genes [22,23]. DNA methylation of CpG islands, in addition to maintaining the compact configuration of chromatin, prevents the integration of transcription factors and thus also produces gene silencing. ...
... DNA methylation of CpG islands, in addition to maintaining the compact configuration of chromatin, prevents the integration of transcription factors and thus also produces gene silencing. Other modifications include acetylation, which favors gene expression; deacetylation, which inhibits gene expression; or modulation of the expression of some non-coding RNAs, such as microRNAs (miRNAs) [20,22,24]. ...
The prevalence and incidence of obesity and the comorbidities linked to it are increasing in the world population. Current therapies for obesity and associated pathologies have proven to cause a broad number of adverse effects and often, they are overpriced or not affordable for all patients. Among the alternatives currently available, natural bioactive compounds stand out. These are frequently contained in pharmaceutical presentations, nutraceutical products, supplements, or functional foods. The clinical evidence for these molecules is increasingly solid, among which epigallocatechin-3-gallate, ellagic acid, resveratrol, berberine, anthocyanins, probiotics, carotenoids, curcumin, silymarin, hydroxy citric acid, and α-lipoic acid stand out. The molecular mechanisms and signaling pathways of these molecules have been shown to interact with the endocrine, nervous, and gastroenteric systems, as well as regulate the expression of multiple genes and, therefore, proteins involved in starvation-satiety processes, activation of brown adipose tissue, increased lipolysis, decreased lipogenesis, and inflammation, beneficial changes in metabolism and improved insulin sensitivity. This review provides a comprehensive view of nature-based therapeutic options to address the increasing prevalence of obesity. It offers a valuable perspective for future research and subsequent clinical practice, addressing everything from the molecular, genetic, and physiological bases to the clinical study of the bioactive compound.
... Epigenetic modifications are modulations in gene expression without changes in the deoxyribonucleic acid (DNA) [21]. This modulation can be induced through DNA modifications, histone alterations, non-coding ribonucleic acids (RNAs), or adenosine triphosphate (ATP)-dependent chromatin remodeling complexes [22]. ...
... DNA methylation occurs because DNA-methyltransferase adds a methyl group to cytokines, generally in regions rich in guanine and cytosine. These regions are called "CpG islands" and are part of the non-coding DNA, but their importance lies in the fact that they are usually located in the promoter region of most genes [22,23]. DNA methylation of CpG islands, in addition to maintaining the compact configuration of chromatin, prevents the integration of transcription factors and thus also produces gene silencing. ...
... DNA methylation of CpG islands, in addition to maintaining the compact configuration of chromatin, prevents the integration of transcription factors and thus also produces gene silencing. Other modifications include acetylation, which favors gene expression; deacetylation, which inhibits gene expression; or modulation of the expression of some non-coding RNAs, such as microRNAs (miRNAs) [20,22,24]. ...
The prevalence and incidence of obesity and the comorbidities linked to it are increasing worldwide. Current therapies for obesity and associated pathologies have proven to cause a broad number of adverse effects, and often, they are overpriced or not affordable for all patients. Among the alternatives currently available, natural bioactive compounds stand out. These are frequently contained in pharmaceutical presentations, nutraceutical products, supplements, or functional foods. The clinical evidence for these molecules is increasingly solid, among which epigallocatechin-3-gallate, ellagic acid, resveratrol, berberine, anthocyanins, probiotics, carotenoids, curcumin, silymarin, hydroxy citric acid, and α-lipoic acid stand out. The molecular mechanisms and signaling pathways of these molecules have been shown to interact with the endocrine, nervous, and gastroenteric systems. They can regulate the expression of multiple genes and proteins involved in starvation-satiety processes, activate the brown adipose tissue, decrease lipogenesis and inflammation, increase lipolysis, and improve insulin sensitivity. This review provides a comprehensive view of nature-based therapeutic options to address the increasing prevalence of obesity. It offers a valuable perspective for future research and subsequent clinical practice, addressing everything from the molecular, genetic, and physiological bases to the clinical study of bioactive compounds.
... Glaucoma can occur at all ages exhibiting a classic (Mendelian) inheritance pattern (i.e., onset before the age of 40) (14,15) or a complex inheritance pattern [i.e., onset after the age of (16,17)]. Therefore, genetic background is considered a precondition that can directly cause or contribute to glaucoma. ...
Glaucoma is the second leading cause of irreversible blindness worldwide. Although genetic background contributes differently to rare early-onset glaucoma (before age 40) or common adult-onset glaucoma, it is now considered an important factor in all major forms of the disease. Genetic and genomic studies, including GWAS, are contributing to identifying novel loci associated with glaucoma or to endophenotypes across ancestries to enrich the knowledge about glaucoma genetic susceptibility. Moreover, new high-throughput functional genomics contributes to defining the relevance of genetic results in the biological pathways and processes involved in glaucoma pathogenesis. Such studies are expected to advance significantly our understanding of glaucoma’s genetic basis and provide new druggable targets to treat glaucoma. This review gives an overview of the role of genetics in the pathogenesis or risk of glaucoma.
... Over the last few years, multiple studies have reported that age-dependent changes in gene expression in different tissues may contribute to high susceptibilities to diseases. [4,[6][7][8] Among these tissues, blood offers many advantages as a sample to identify potential biomarker signatures of aging, including convenient acquisition, and reducing the burden of making multiple physiological and clinical assessments. [3,4] Moreover, biomarkers in blood samples may systematically reflect the age-related changes in the internal environment since blood flows through any organ. ...
Older age is one of the most important shared risk factors for multiple chronic diseases, increasing the medical burden to contemporary societies. Current research focuses on identifying aging biomarkers to predict aging trajectories and developing interventions aimed at preventing and delaying the progression of multimorbidity with aging. Here, a transcriptomic changes analysis of whole blood genes with age was conducted. The age-related whole blood gene-expression profiling datasets were downloaded from the Gene Expression Omnibus (GEO) database. We screened the differentially expressed genes (DEGs) between healthy young and old individuals and performed functional enrichment analysis. Cytoscape with Cytohubba and MCODE was used to perform an interaction network of DEGs and identify hub genes. In addition, ROC curves and correlation analysis were used to evaluate the accuracy of hub genes. In total, we identified 29 DEGs between young and old samples that were enriched mainly in immunoglobulin binding and complex, humoral immune response, and immune response-activating signaling pathways. In combination with the PPI network and topological analysis, 4 hub genes (IGLL5, Jchain, POU2AF1, and Bach2) were identified. Pearson analysis showed that the expression changes of these hub genes were highly correlated with age. Among them, 3 hub genes (IGLL5, POU2AF1, and Bach2) were identified with good accuracy (AUC score > 0.7), indicating that these genes were the best indicators of age. Together, our results provided potential biomarkers IGLL5, POU2AF1, and Bach2 to identify individuals at high early risk of age-related disease to be targeted for early interventions and contribute to understanding the molecular mechanisms in the progression of aging.
