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Age-related methylation changes. Top: The youthful DNA methylation pattern: promoter hypomethylation enables gene transcription, while transposable elements (TEs) are firmly anchored by hypermethylation. Bottom: Old age methylation: heavy promoter methylation, silencing gene expression, while genome-wide hypomethylation enables neuronal cell cycle reentry and TE mobilization.
Contexts in source publication
Context 1
... age disrupts the methylome, enabling both TE mobilization and cell cycle reactivation in mature neurons. Indeed, aging was demonstrated to remodel the genomic methylation landscape, imprinting a typical pattern marked by genome-wide hypomethylation and promoter-specific hypermeth- ylation ( Mastroeni et al., 2010) (Figure 1). The age-related methylation shift is probably triggered by the intracellular iron and HCys accumulation. ...
Context 2
... contrast, microRNA-29 (miR-29) restores the previous methylation land- scape by directly targeting DNMT 3A/3B and DNMT1, while at the same time lowering intracellular iron (Sfera et al., 2017). Interestingly, the selective sero- From the epigenetic view point, lithium increases global DNA methyla- tion and lowers the methylation of selective promoters, including the brain derived neurotrophic factor (BDNF), enabling its expression. ...
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Citations
... However, the prevalence of ACE2's function in physiology, especially in the cardiovascular and renal systems, renders ACE2 inhibitors risky in a clinical setting [36,37]. Hence, further studies on compounds like curcumin and 8-hydroquinone, which may activate DNMTs to silence ACE2 within viable clinical doses [38][39][40], may be beneficial. Currently, several epigenetic-based ...
... However, the prevalence of ACE2's function in physiology, especially in the cardiovascular and renal systems, renders ACE2 inhibitors risky in a clinical setting [36,37]. Hence, further studies on compounds like curcumin and 8-hydroquinone, which may activate DNMTs to silence ACE2 within viable clinical doses [38][39][40], may be beneficial. Currently, several epigenetic-based clinical trials against COVID-19 are being pursued globally; some of them are listed in Table 1. ...
Developmental biology is intricately regulated by epigenetics and metabolism but the mechanisms are not completely understood. The situation becomes even more complicated during diseases where all three phenomena are dysregulated. A salient example is COVID-19, where the death toll exceeded 6.96 million in 4 years, while the virus continues to mutate into different variants and infect people. Early evidence during the pandemic showed that the host’s immune and inflammatory responses to COVID-19 (like the cytokine storm) impacted the host’s metabolism, causing damage to the host’s organs and overall physiology. The involvement of angiotensin-converting enzyme 2 (ACE2), the pivotal host receptor for the SARS-CoV-2 virus, was identified and linked to epigenetic abnormalities along with other contributing factors. Recently, studies have revealed stronger connections between epigenetics and metabolism in COVID-19 that impact development and accelerate aging. Patients manifest systemic toxicity, immune dysfunction and multi-organ failure. Single-cell multiomics and other state-of-the-art high-throughput studies are only just beginning to demonstrate the extent of dysregulation and damage. As epigenetics and metabolism directly impact development, there is a crucial need for research implementing cutting-edge technology, next-generation sequencing, bioinformatics analysis, the identification of biomarkers and clinical trials to help with prevention and therapeutic interventions against similar threats in the future.
... In vitro data suggest that use of vitamin D and quercetin would ameliorate COVID-19 severity by inhibiting the expression of ACE2 and furin [192,193]. Curcumin and 8hydroxyquinolones may silence ACE2 and interferon genes by activation of DNMTs within viable clinical doses [194][195][196]. Among the notable drugs those can modulate DNA methylation and histone acetylation capacities are sulforaphane [197] and thymoquinone [198] that inhibit HDAC, lupeol and β-sitosterol from P. fotida plant extract that repress DNMTs, IL-6, IL1-β, TNF-α [199], and procyanidin B2 inhibits DNMTs [200]. ...
COVID-19 has caused numerous deaths as well as imposed social isolation and upheaval world-wide. Although, the genome and the composition of the virus, the entry process and replication mechanisms are well investigated from by several laboratories across the world, there are many unknown remaining questions. For example, what are the functions of membrane lipids during entry, packaging and exit of virus particles? Also, the metabolic aspects of the infected tissue cells are poorly understood. In the course of virus replication and formation of virus particles within the host cell, the enhanced metabolic activities of the host is directly proportional to viral loads. The epigenetic landscape of the host cells is also altered, particularly the expression/repression of genes associated with cellular metabolism as well as cellular processes that are antagonistic to the virus. Metabolic pathways are enzyme driven processes and the expression profile and mechanism of regulations of the respective genes encoding those enzymes during the course of pathogen invasion might be highly informative on the course of the disease. Recently, the metabolic profile of the patients' sera have been analysed from few patients. In view of this, and to gain further insights into the roles that epigenetic mechanisms might play in this scenario in regulation of metabolic pathways during the progression of COVID-19 are discussed and summarised in this contribution for ensuring best therapy.
... Another candidate for epigenetic silencing of the ACE2 and interferon genes is curcumin. 62 Curcumin is a potent activator of DNA methyltransferases in viable clinical doses and has ferritinreducing effects. [63][64][65] This becomes important when considering that high ferritin values in patients with COVID-19 are associated with greater severity of the disease. ...
Objective:
The present article presents a literature review concerning the microbiota of breast milk and the influence of epigenetics in the susceptibility to COVID-19.
Methods:
A literature review.
Results:
Breastfeeding transfers microbiota, nutrients, diverse white blood cells, prebiotics, hormones, and antibodies to the baby, which provide short- and long-term immunological protection against several infectious, gastrointestinal, and respiratory illnesses. The little evidence available shows that breast milk very rarely carries the SARS-CoV-2 virus, and even in those cases, it has been discarded as the source of contagion.
Conclusion:
The reviewed studies show evidence of a beneficial effect of breastfeeding and highlights its importance on the current pandemic due to the immune reinforcement that it provides. Breastfed individuals showed better clinical response due to the influence on the microbiota and to the nutritional and immune contribution provided by breast milk, compared with those who were not breastfed.
... Epigenetics refers to the regulation of gene expression, orchestrated by chromatin modifications, DNA structure alteration and non-coding of RNAs independent of the DNA sequence transformation (Christopher et al., 2017). In the CNS, emerging evidence demonstrates that epigenetic regulation plays a critical part in multiple pathological and physiological processes, such as proliferation, differentiation, survival and regeneration (Kameda et al., 2018;Sfera et al., 2018). SCI is accompanied by a series of epigenetic landmark alterations, some strongly related to processes such as axon regeneration, glial activation, neurogenesis and ependymal cell reprogramming (Li et al., 2016). ...
Spinal cord injury that results in severe neurological disability is often incurable. The poor clinical outcome of spinal cord injury is mainly caused by the failure to reconstruct the injured neural circuits. Several intrinsic and extrinsic determinants contribute to this inability to reconnect. Epigenetic regulation acts as the driving force for multiple pathological and physiological processes in the central nervous system by modulating the expression of certain critical genes. Recent studies have demonstrated that post-SCI alteration of epigenetic landmarks is strongly associated with axon regeneration, glial activation and neurogenesis. These findings not only establish a theoretical foundation for further exploration of spinal cord injury, but also provide new avenues for the clinical treatment of spinal cord injury. This review focuses on the epigenetic regulation in axon regeneration and secondary spinal cord injury. Together, these discoveries are a selection of epigenetic-based prognosis biomarkers and attractive therapeutic targets in the treatment of spinal cord injury.
... Nevertheless, Ilie and Smith (2019) found that the average vitamin D level in European countries correlates negatively with the mortality rate of SARS-CoV-2, and this supports the still somewhat preliminary recommendation of using vitamin D as a preventive intervention for SARS-CoV-2. Other candidates for epigenetic silencing of ACE2 and interferon genes are curcumin, deferasirox, and 8-hydroxyquinolones (8HQ) (Sfera et al., 2018). Curcumin is a potent activator of DNA methyltransferases in viable clinical doses (Hassan et al., 2019). ...
The recent pandemic SARS-CoV-2 outbreak affects all kinds of individuals worldwide. The health, social, and economic impacts of the pandemic are dramatic, and vaccines or specific treatment options are not yet available. The only approaches that we currently have available to stop the epidemic are those of classical epidemic control, such as case isolation, contact tracing and quarantine, physical distancing, and hygiene measures. It is therefore essential to find further preventive measures and possible interventions that can slow down the number of infected individuals and decrease the severity of disease when affected by SARS-CoV-2. It seems that epigenetic mechanisms are an important part of the pathophysiology and illness severity of COVID-19. These mechanisms have been identified in SARS-CoV-2 but also in other viral infections. If and when these mechanisms are confirmed, then epigenetic interventions influencing DNA methylation could be indicated as primary and/or secondary preventive options.
... Recent studies reveal transposable-element-driven genomic mosaicism in the mammalian brain, and hint that this process may be due, in part, both to environmental factors and the aging process via epigenetic changes. [5,16,17,18,19]. These epigenetic variables may include changes in: the miRNA network, DNA methylation, histone modification, and perhaps more [20,21,22,23]. ...
This year, 2018, marks the 35th anniversary of Barbara McClintock being awarded the Nobel Prize in Physiology or Medicine for her discovery of genetic transposition or “jumping genes.” (1, 2, 3, 4) Recent studies hint that “jumping genes” (retrotransposons) may be profoundly important to the field of neuroscience. (5)
