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Trends in Endocrinology and Metabolism:... Sep 2019Epigenetics can be defined as 'the structural adaptation of chromosomal regions so as to register, signal, or perpetuate altered activity states.' Increased... (Review)
Review
Epigenetics can be defined as 'the structural adaptation of chromosomal regions so as to register, signal, or perpetuate altered activity states.' Increased transcription of key regulatory, metabolic, and myogenic genes is an early response to exercise and is important in mediating subsequent adaptations in skeletal muscle. DNA hypomethylation and histone hyperacetylation are emerging as important crucial events for increased transcription. The complex interactions between multiple epigenetic modifications and their regulation by metabolic changes and signaling events during exercise, with implications for enhanced understanding of the acute and chronic adaptations to exercise, are questions for further investigation.
Topics: DNA Methylation; Epigenesis, Genetic; Exercise; Histones; Humans; Muscle, Skeletal
PubMed: 31279665
DOI: 10.1016/j.tem.2019.06.002 -
Aging Nov 2021The search continues for possible interventions that delay and/or reverse biological aging, resulting in extended healthspan and lifespan. Interventions delaying aging...
Rejuvant®, a potential life-extending compound formulation with alpha-ketoglutarate and vitamins, conferred an average 8 year reduction in biological aging, after an average of 7 months of use, in the TruAge DNA methylation test.
The search continues for possible interventions that delay and/or reverse biological aging, resulting in extended healthspan and lifespan. Interventions delaying aging in animal models are well established; however, most lack validation in humans. The length of human lifespan makes it impractical to perform survival analysis. Instead, aging biomarkers, such as DNA methylation (DNAm) clocks, have been developed to monitor biological age. Herein we report a retrospective analysis of DNA methylation age in 42 individuals taking Rejuvant®, an alpha-ketoglutarate based formulation, for an average period of 7 months. DNAm testing was performed at baseline and by the end of treatment with Rejuvant® supplementation. Remarkably, individuals showed an average decrease in biological aging of 8 years (p-value=6.538x10). Furthermore, the supplementation with Rejuvant® is robust to individual differences, as indicated by the fact that a large majority of participants decreased their biological age. Moreover, we found that Rejuvant® is of additional benefit to chronologically and biologically older individuals. While continued testing, particularly in a placebo-controlled design, is required, the nearly 8-year reversal in the biological age of individuals taking Rejuvant® for 4 to 10 months is noteworthy, making the natural product cocktail an intriguing candidate to affect human aging.
Topics: Adult; Aged; Aging; DNA Methylation; Dietary Supplements; Female; Geroscience; Humans; Ketoglutaric Acids; Male; Middle Aged; Vitamins
PubMed: 34847066
DOI: 10.18632/aging.203736 -
Progress in Molecular Biology and... 2018DNA methylation has been an important area of research in the study of molecular mechanism to psychiatric disorders. Recent evidence has suggested that abnormalities in... (Review)
Review
DNA methylation has been an important area of research in the study of molecular mechanism to psychiatric disorders. Recent evidence has suggested that abnormalities in global methylation, methylation of genes, and pathways could play a role in the etiology of many forms of mental illness. In this article, we review the mechanisms of DNA methylation, including the genetic and environmental factors affecting methylation changes. We report and discuss major findings regarding DNA methylation in psychiatric patients, both within the context of global methylation studies and gene-specific methylation studies. Finally, we discuss issues surrounding data quality improvement, the limitations of current methylation analysis methods, and the possibility of using DNA methylation-based treatment for psychiatric disorders in the future.
Topics: Brain; DNA Methylation; Genetic Association Studies; Genetic Predisposition to Disease; Genome, Human; Humans; Mental Disorders
PubMed: 29933950
DOI: 10.1016/bs.pmbts.2018.01.006 -
Nature Biotechnology Aug 2022
Topics: DNA Methylation; Epigenomics
PubMed: 35945440
DOI: 10.1038/s41587-022-01433-9 -
Handbook of Clinical Neurology 2021Animal and humans exposed to stress early in life are more likely to suffer from long-term behavioral, mental health, metabolic, immune, and cardiovascular health... (Review)
Review
Animal and humans exposed to stress early in life are more likely to suffer from long-term behavioral, mental health, metabolic, immune, and cardiovascular health consequences. The hypothalamus plays a nodal role in programming, controlling, and regulating stress responses throughout the life course. Epigenetic reprogramming in the hippocampus and the hypothalamus play an important role in adapting genome function to experiences and exposures during the perinatal and early life periods and setting up stable phenotypic outcomes. Epigenetic programming during development enables one genome to express multiple cell type identities. The most proximal epigenetic mark to DNA is a covalent modification of the DNA itself by enzymatic addition of methyl moieties. Cell-type-specific DNA methylation profiles are generated during gestational development and define cell and tissue specific phenotypes. Programming of neuronal phenotypes and sex differences in the hypothalamus is achieved by developmentally timed rearrangement of DNA methylation profiles. Similarly, other stations in the life trajectory such as puberty and aging involve predictable and scheduled reorganization of DNA methylation profiles. DNA methylation and other epigenetic marks are critical for maintaining cell-type identity in the brain, across the body, and throughout life. Data that have emerged in the last 15 years suggest that like its role in defining cell-specific phenotype during development, DNA methylation might be involved in defining experiential identities, programming similar genes to perform differently in response to diverse experiential histories. Early life stress impact on lifelong phenotypes is proposed to be mediated by DNA methylation and other epigenetic marks. Epigenetic marks, as opposed to genetic mutations, are reversible by either pharmacological or behavioral strategies and therefore offer the potential for reversing or preventing disease including behavioral and mental health disorders. This chapter discusses data testing the hypothesis that DNA methylation modulations of the HPA axis mediate the impact of early life stress on lifelong behavioral and physical phenotypes.
Topics: Animals; DNA Methylation; Epigenesis, Genetic; Female; Humans; Hypothalamo-Hypophyseal System; Male; Phenotype; Pituitary-Adrenal System; Pregnancy; Stress, Psychological
PubMed: 34225925
DOI: 10.1016/B978-0-12-820107-7.00008-2 -
Genetics in Medicine : Official Journal... Aug 2023HNRNPU haploinsufficiency is associated with developmental and epileptic encephalopathy 54. This neurodevelopmental disorder is characterized by developmental delay,...
PURPOSE
HNRNPU haploinsufficiency is associated with developmental and epileptic encephalopathy 54. This neurodevelopmental disorder is characterized by developmental delay, intellectual disability, speech impairment, and early-onset epilepsy. We performed genome-wide DNA methylation (DNAm) analysis in a cohort of individuals to develop a diagnostic biomarker and gain functional insights into the molecular pathophysiology of HNRNPU-related disorder.
METHODS
DNAm profiles of individuals carrying pathogenic HNRNPU variants, identified through an international multicenter collaboration, were assessed using Infinium Methylation EPIC arrays. Statistical and functional correlation analyses were performed comparing the HNRNPU cohort with 56 previously reported DNAm episignatures.
RESULTS
A robust and reproducible DNAm episignature and global DNAm profile were identified. Correlation analysis identified partial overlap and similarity of the global HNRNPU DNAm profile to several other rare disorders.
CONCLUSION
This study demonstrates new evidence of a specific and sensitive DNAm episignature associated with pathogenic heterozygous HNRNPU variants, establishing its utility as a clinical biomarker for the expansion of the EpiSign diagnostic test.
Topics: Humans; DNA Methylation; Epigenomics; Phenotype; Neurodevelopmental Disorders; Biomarkers
PubMed: 37120726
DOI: 10.1016/j.gim.2023.100871 -
Stem Cell Reviews and Reports Feb 2018Epigenetics can be explored at different levels and can be divided into two major areas: epigenetics of nuclear-encoded DNA and epigenetics of mitochondrial-encoded DNA.... (Review)
Review
Epigenetics can be explored at different levels and can be divided into two major areas: epigenetics of nuclear-encoded DNA and epigenetics of mitochondrial-encoded DNA. In epigenetics of nuclear-encoded DNA, the main roles are played by DNA methylation, changes in histone structure and several types of non-coding RNAs. Mitochondrial epigenetics seems to be similar in the aspect of DNA methylation and to some extent in the role of non-coding RNAs but differs significantly in changes in components coiling DNA. Nuclear DNA is coiled around histones, but mitochondrial DNA, together with associated proteins, is located in mitochondrial pseudocompartments called nucleoids. It has been shown that mitochondrial epigenetic mechanisms influence cell fate, transcription regulation, cell division, cell cycle, physiological homeostasis, bioenergetics and even pathologies, but not all of these mechanisms have been explored in stem cells. The main issue is that most of these mechanisms have only recently been discovered in mitochondria, while improvements in methodology, especially next-generation sequencing, have enabled in-depth studies. Because studies exploring mitochondria from other aspects show that mitochondria are crucial for the normal behavior of stem cells, it is suggested that precise mitochondrial epigenetics in stem cells should be studied more intensively.
Topics: Animals; DNA Methylation; DNA, Mitochondrial; Epigenesis, Genetic; Humans; Mitochondria
PubMed: 28980199
DOI: 10.1007/s12015-017-9771-z -
Journal of Integrative Plant Biology Dec 2022DNA methylation plays essential homeostatic functions in eukaryotic genomes. In animals, DNA methylation is also developmentally regulated and, in turn, regulates... (Review)
Review
DNA methylation plays essential homeostatic functions in eukaryotic genomes. In animals, DNA methylation is also developmentally regulated and, in turn, regulates development. In the past two decades, huge research effort has endorsed the understanding that DNA methylation plays a similar role in plant development, especially during sexual reproduction. The power of whole-genome sequencing and cell isolation techniques, as well as bioinformatics tools, have enabled recent studies to reveal dynamic changes in DNA methylation during germline development. Furthermore, the combination of these technological advances with genetics, developmental biology and cell biology tools has revealed functional methylation reprogramming events that control gene and transposon activities in flowering plant germlines. In this review, we discuss the major advances in our knowledge of DNA methylation dynamics during male and female germline development in flowering plants.
Topics: Animals; DNA Methylation; Epigenesis, Genetic; Germ Cells; Reproduction
PubMed: 36478632
DOI: 10.1111/jipb.13422 -
Physiologia Plantarum Jan 2022Fleshy fruit, the most economical and nutritional value unique to flowering plants, is an important part of our daily diet. Previous studies have shown that fruit... (Review)
Review
Fleshy fruit, the most economical and nutritional value unique to flowering plants, is an important part of our daily diet. Previous studies have shown that fruit ripening is regulated by transcription factors and the plant hormone ethylene, but recent research has also shown that epigenetics also plays an essential role, especially DNA methylation. DNA methylation is the process of transferring -CH3 to the fifth carbon of cytosine residues under the action of methyltransferase to form 5-methylcytosine (5-mC). So far, most works have been focused on tomato. Tomato ripening is dynamically regulated by DNA methylation and demethylation, but the understanding of this mechanism is still in its infancy. The dysfunction of a DNA demethylase, DEMETER-like DNA demethylases 2 (DML2), prevents the ripening of tomato fruits, but immature fruits ripen prematurely under the action of DNA methylation inhibitors. Additionally, studies have shown that the relationship between fruit quality and DNA methylation is not linear, but the specific molecular mechanism is still unclear. Here, we review the recent advances in the role of DNA methylation in tomato fruit ripening, the interaction of ripening transcription factors and DNA methylation, and its effects on quality. Then, a number of questions for future research of DNA methylation regulation in tomato fruit ripening is proposed.
Topics: DNA Methylation; Ethylenes; Fruit; Gene Expression Regulation, Plant; Solanum lycopersicum; Plant Proteins
PubMed: 35040145
DOI: 10.1111/ppl.13627 -
Progress in Molecular Biology and... 2023With aging, prevalence of obesity, hypertension, diabetes and renal diseases have increased globally. Over the last two decades, the prevalence of renal diseases has...
With aging, prevalence of obesity, hypertension, diabetes and renal diseases have increased globally. Over the last two decades, the prevalence of renal diseases has been intensely increasing. Renal disease and renal programming are regulated by epigenetic modifications like DNA methylation and histone modifications. Environmental factors have significant role in the pathophysiology of renal disease progression. Understanding the potential of epigenetic regulation of gene expression may be useful in renal disease prognosis, diagnosis and provides novel therapeutic measures. In a nutshell, this chapter talks about the role of epigenetic mechanisms-DNA methylation, histone modification, and noncoding RNA in different renal diseases. These include diabetic kidney disease, diabetic nephropathy, renal fibrosis, etc.
Topics: Humans; Epigenesis, Genetic; Kidney Diseases; Kidney; DNA Methylation; Aging
PubMed: 37225324
DOI: 10.1016/bs.pmbts.2023.02.013