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Aging epigenetics histone

Amit Berson, Raffaella Nativio, Shelley L Berger, Nancy M Bonini
Mechanisms of epigenetic regulation, including DNA methylation, chromatin remodeling, and histone post-translational modifications, are involved in multiple aspects of neuronal function and development. Recent discoveries have shed light on critical functions of chromatin in the aging brain, with an emerging realization that the maintenance of a healthy brain relies heavily on epigenetic mechanisms. Here, we present recent advances, with a focus on histone modifications and the implications for several neurodegenerative diseases including Alzheimer's disease (AD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS)...
June 6, 2018: Trends in Neurosciences
Jolie D Barter, Thomas C Foster
Gene expression in the aging brain depends on transcription signals generated by senescent physiology, interacting with genetic and epigenetic programs. In turn, environmental factors influence epigenetic mechanisms, such that an epigenetic-environmental link may contribute to the accumulation of cellular damage, susceptibility or resilience to stressors, and variability in the trajectory of age-related cognitive decline. Epigenetic mechanisms, DNA methylation and histone modifications, alter chromatin structure and the accessibility of DNA...
June 1, 2018: Neuroscientist: a Review Journal Bringing Neurobiology, Neurology and Psychiatry
Tara Nguyen, Gerard E Li, Hui Chen, Charles G Cranfield, Kristine C McGrath, Catherine Anne Gorrie
Electronic cigarette (e-cigarette) use is on the rise worldwide and is particularly attractive to young people and as a smoking substitute by pregnant woman. There is a perception in pregnant woman and women of child-bearing age that the use of e-cigarettes (vaping) is safer than smoking tobacco cigarettes during pregnancy. However, there is little evidence to support this perception. Here, we examined the offspring from mouse dams that had been exposed during and after pregnancy to ambient air (sham) (n=8), e-cigarette aerosols with nicotine (n=8) or e-cigarette aerosols without nicotine (n=8)...
June 4, 2018: Chemical Research in Toxicology
Zaijun Ma, Hui Wang, Yuping Cai, Han Wang, Kongyan Niu, Xiaofen Wu, Huanhuan Ma, Yun Yang, Wenhua Tong, Feng Liu, Zhandong Liu, Yaoyang Zhang, Rui Liu, Zheng-Jiang Zhu, Nan Liu
Epigenetic alteration has been implicated in aging. However, the mechanism by which epigenetic change impacts aging remains to be understood. H3K27me3, a highly conserved histone modification signifying transcriptional repression, is marked and maintained by Polycomb Repressive Complexes (PRCs). Here, we explore the mechanism by which age-modulated increase of H3K27me3 impacts adult lifespan. Using Drosophila , we reveal that aging leads to loss of fidelity in epigenetic marking and drift of H3K27me3 and consequential reduction in the expression of glycolytic genes with negative effects on energy production and redox state...
May 29, 2018: ELife
Danny El-Nachef, Kyohei Oyama, Yun-Yu Wu, Miles Freeman, Yiqiang Zhang, W Robb MacLellan
Mammalian cardiac myocytes (CMs) stop proliferating soon after birth and subsequent heart growth comes from hypertrophy, limiting the adult heart's regenerative potential after injury. The molecular events that mediate CM cell cycle exit are poorly understood. To determine the epigenetic mechanisms limiting CM cycling in adult CMs (ACMs) and whether trimethylation of lysine 9 of histone H3 (H3K9me3), a histone modification associated with repressed chromatin, is required for the silencing of cell cycle genes, we developed a transgenic mouse model where H3K9me3 is specifically removed in CMs by overexpression of histone demethylase, KDM4D...
May 22, 2018: Journal of Molecular and Cellular Cardiology
Marina Mitjans, Jan Seidel, Martin Begemann, Fabian Bockhop, Jorge Moya-Higueras, Vikas Bansal, Janina Wesolowski, Anna Seelbach, Manuel Ignacio Ibáñez, Fatka Kovacevic, Oguzhan Duvar, Lourdes Fañanás, Hannah-Ulrike Wolf, Generós Ortet, Peter Zwanzger, Verena Klein, Ina Lange, Andreas Tänzer, Manuela Dudeck, Lars Penke, Ludger Tebartz van Elst, Robert A Bittner, Richard Schmidmeier, Roland Freese, Rüdiger Müller-Isberner, Jens Wiltfang, Thomas Bliesener, Stefan Bonn, Luise Poustka, Jürgen L Müller, Bárbara Arias, Hannelore Ehrenreich
Early exposure to negative environmental impact shapes individual behavior and potentially contributes to any mental disease. We reported previously that accumulated environmental risk markedly decreases age at schizophrenia onset. Follow-up of matched extreme group individuals (≤1 vs. ≥3 risks) unexpectedly revealed that high-risk subjects had >5 times greater probability of forensic hospitalization. In line with longstanding sociological theories, we hypothesized that risk accumulation before adulthood induces violent aggression and criminal conduct, independent of mental illness...
May 24, 2018: Molecular Psychiatry
J L Pierce, D L Begun, J J Westendorf, M E McGee-Lawrence
Bone is a complex endocrine organ that facilitates structural support, protection to vital organs, sites for hematopoiesis, and calcium homeostasis. The bone marrow microenvironment is a heterogeneous niche consisting of multipotent musculoskeletal and hematopoietic progenitors and their derivative terminal cell types. Amongst these progenitors, bone marrow mesenchymal stem/stromal cells (BMSCs) may differentiate into osteogenic, adipogenic, myogenic, and chondrogenic lineages to support musculoskeletal development as well as tissue homeostasis, regeneration and repair during adulthood...
May 18, 2018: Bone
Bryan M McClarty, Daniel W Fisher, Hongxin Dong
Purpose of the review: Antipsychotics are commonly prescribed for the treatment of psychosis as well as behavioral and psychological symptoms of dementia (BPSD) in elderly patients. However, elderly patients often experience decreased antipsychotic efficacy and increased side effects, though the mechanisms underlying these changes with age are not clear. Recent findings: Although aging can affect drug metabolism and clearance through changes in renal and hepatic function, additional pharmacokinetic and pharmacodynamic changes due to aging-induced epigenetic alterations also impact processes important for antipsychotic function...
March 2018: Current Treatment Options in Psychiatry
Aseel Eid, Syed Waseem Bihaqi, Christopher Hemme, John M Gaspar, Ronald P Hart, Nasser H Zawia
AIM: Early life exposure to lead (Pb) has been shown to increase late life biomarkers involved in Alzheimer's disease (AD) pathology. Here, we tested the hypothesis that latent over expression of AD-related genes may be regulated through histone activation pathways. METHODS: Chromatin immunoprecipitation sequencing was used to map the histone activation mark (H3K9Ac) to the mouse genome in developmentally Pb exposed mice on postnatal days 20, 270 and 700. RESULTS: Exposure to Pb resulted in a global downregulation of H3K9Ac across the lifespan; except in genes associated with the Alzheimer pathway...
May 3, 2018: Epigenomics
Minesh Kapadia, M Firoz Mian, Bernadeta Michalski, Amber Azam, Donglai Ma, Patrick Salwierz, Adam Christopher, Elyse Rosa, Iva Zovkic, Paul Forsythe, Margaret Fahnestock, Boris Sakic
The triple-transgenic (3xTg-AD) mouse strain is a valuable model of Alzheimer's disease (AD) because it develops both amyloid-β (Aβ) and tau brain pathology. However, 1-year-old 3xTg-AD males no longer show plaques and tangles, yet early in life, they exhibit diverse signs of systemic autoimmunity. The current study aimed to address whether females, which exhibit more severe plaque/tangle pathology at 1 year of age, show similar autoimmune phenomena and if so, whether these immunological changes coincide with prodromal markers of AD pathology, markers of learning and memory formation and epigenetic markers of neurodegenerative disease...
April 25, 2018: Journal of Alzheimer's Disease: JAD
Peggie Cheung, Francesco Vallania, Hayley C Warsinske, Michele Donato, Steven Schaffert, Sarah E Chang, Mai Dvorak, Cornelia L Dekker, Mark M Davis, Paul J Utz, Purvesh Khatri, Alex J Kuo
Post-translational modifications of histone proteins and exchanges of histone variants of chromatin are central to the regulation of nearly all DNA-templated biological processes. However, the degree and variability of chromatin modifications in specific human immune cells remain largely unknown. Here, we employ a highly multiplexed mass cytometry analysis to profile the global levels of a broad array of chromatin modifications in primary human immune cells at the single-cell level. Our data reveal markedly different cell-type- and hematopoietic-lineage-specific chromatin modification patterns...
April 21, 2018: Cell
P J Stover, W P T James, A Krook, C Garza
Understanding the physiological and metabolic underpinnings that confer individual differences in responses to diet and diet-related chronic disease is essential to advance the field of nutrition. This includes elucidating the differences in gene expression that are mediated through programming of the genome through epigenetic chromatin modifications. Epigenetic landscapes are influenced by age, genetics, toxins and other environmental factors, including dietary exposures and nutritional status. Epigenetic modifications influence transcription and genome stability, are established during development with life-long consequences...
April 29, 2018: Journal of Internal Medicine
Luz Jubierre, Carlos Jiménez, Eric Rovira, Aroa Soriano, Constantino Sábado, Luis Gros, Anna Llort, Raquel Hladun, Josep Roma, Josep Sánchez de Toledo, Soledad Gallego, Miguel F Segura
Approximately 15,000 new cases of pediatric cancer are diagnosed yearly in Europe, with 8-10% corresponding to neuroblastoma, a rare disease with an incidence of 8-9 cases per million children <15 years of age. Although the survival rate for low-risk and intermediate-risk patients is excellent, half of children with high-risk, refractory, or relapsed tumors will be cured, and two-thirds of the other half will suffer major side effects and life-long disabilities. Epigenetic therapies aimed at reversing the oncogenic alterations in chromatin structure and function are an emerging alternative against aggressive tumors that are or will become resistant to conventional treatments...
April 27, 2018: Experimental & Molecular Medicine
Shufei Song, F Brad Johnson
Aging and age-related diseases pose some of the most significant and difficult challenges to modern society as well as to the scientific and medical communities. Biological aging is a complex, and, under normal circumstances, seemingly irreversible collection of processes that involves numerous underlying mechanisms. Among these, chromatin-based processes have emerged as major regulators of cellular and organismal aging. These include DNA methylation, histone modifications, nucleosome positioning, and telomere regulation, including how these are influenced by environmental factors such as diet...
April 9, 2018: Genes
Chunli Wang, Fei Wang, Zhen Li, Qing Cao, Liya Huang, Shuyan Chen
BACKGROUND: Cellular aging may be associated with epigenetics. Methyl-CpG-binding protein 2 (MeCP2) and sirtuin 1 (SIRT1) are two important epigenetic factors. Our former work demonstrated that MeCP2 expression increased and SIRT1 expression decreased in senescent endothelial progenitor cells (EPCs). This article aims to reveal the epigenetic regulation caused by MeCP2 in EPCs and discuss its mechanism. METHODS: Tube formation assay and cell apoptosis detection were used to evaluate the function of senescent EPCs induced by MeCP2 overexpression...
April 3, 2018: Stem Cell Research & Therapy
Nathan Lo, Stephen J Simpson, Gregory A Sword
Developmental plasticity is a key driver of the extraordinary ecological success of insects. Epigenetic mechanisms provide an important link between the external stimuli that initiate polyphenisms, and the stable changes in gene expression that govern alternative insect morphs. We review the epigenetics of orthopteroid insects, focussing on recent research on locusts and termites, two groups which display high levels of phenotypic plasticity, and for which genome sequences have become available in recent years...
February 2018: Current Opinion in Insect Science
Cristina-Sorina Cătană, Atanas G Atanasov, Ioana Berindan-Neagoe
In recent years, there has been a great deal of attention toward the molecular machinery relevant to age-related progression controlled through the external intervention of polyphenols- an epigenetic-modulating diet. Natural products modulate cellular longevity through histone post-translational modification and can also induce the upregulation of autophagy, thus reducing the level of acetyl coenzyme A (AcCoA). In addition, the effect of caloric restriction (CR) on cancer-related chronic inflammation is of great significance in aging...
March 27, 2018: Biotechnology Advances
Swarna Raman, Una FitzGerald, J Mary Murphy
Osteoarthritis (OA), a degenerative disease of diarthrodial joints, is influenced by mechanical and inflammatory factors with aging, obesity, chronic injuries, and secondary diseases thought to be major factors driving the process of articular cartilage degeneration. Chondrocytes, the cellular component of cartilage, reside in an avascular environment and normally have limited potential to replicate. However, extrinsic factors such as injury to the joint or intrinsic alterations to the chondrocytes themselves can lead to an altered phenotype and development of OA...
2018: Frontiers in Bioengineering and Biotechnology
Alice S Mims, Anjali Mishra, Shelley Orwick, James Blachly, Rebecca B Klisovic, Ramiro Garzon, Alison R Walker, Steven M Devine, Katherine J Walsh, Sumithira Vasu, Susan Whitman, Guido Marcucci, Daniel Jones, Nyla A Heerema, Gerard Lozanski, Michael A Caligiuri, Clara D Bloomfield, John C Byrd, Richard Piekarz, Michael R Grever, William Blum
KMT2A partial tandem duplication occurs in approximately 5-10% of patients with acute myeloid leukemia and is associated with adverse prognosis. KMT2A wild type is epigenetically silenced in KMT2A partial tandem duplication; re-expression can be induced with DNA methyltransferase and/or histone deacetylase inhibitors in vitro, sensitizing myeloid blasts to chemotherapy. We hypothesized that epigenetic silencing of KMT2A wildtype contributes to KMT2A partial tandem duplication-associated leukemogenesis and pharmacologic re-expression activates apoptotic mechanisms important for chemo-response...
March 22, 2018: Haematologica
Khaled Elmasry, Riyaz Mohamed, Isha Sharma, Nehal M Elsherbiny, Yutao Liu, Mohamed Al-Shabrawey, Amany Tawfik
To study Hyperhomocysteinemia (HHcy)-induced epigenetic modifications as potential mechanisms of blood retinal barrier (BRB) dysfunction, retinas isolated from three- week-old mice with elevated level of Homocysteine (Hcy) due to lack of the enzyme cystathionine β-synthase ( cbs-/- , cbs+/- and cbs+/+ ), human retinal endothelial cells (HRECs), and human retinal pigmented epithelial cells (ARPE-19) treated with or without Hcy were evaluated for (1) histone deacetylases (HDAC), (2) DNA methylation (DNMT), and (3) miRNA analysis...
February 27, 2018: Oncotarget
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