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Chromatin aging

Andres Matoso, Binny Khandakar, Songyang Yuan, Tony Wu, Li J Wang, Kara A Lombardo, Shamlal Mangray, Abul Ala Syed Rifat Mannan, Evgeny Yakirevich
Gender confirmation surgery (GCS) is increasingly common in persons with gender dysphoria. We describe changes seen in gonads from individuals seeking male to female physical adaptation. We studied 99 orchiectomies from 50 persons. The average age was 33years (range: 21-63). Eighty six of 99 (86.8%) testes were normal in size with an average size of 3.87cm (range: 3.0-5.5). Thirteen of 99 (13.1%) testes were hypotrophic and measured up to 2.5cm. Seminiferous tubules were reduced in diameter compared to controls (0...
March 16, 2018: Human Pathology
Lan Hai, Maria M Szwarc, Bin He, David M Lonard, Ramakrishna Kommagani, Francesco J DeMayo, John P Lydon
Speckle-type poz protein (SPOP) is an E3-ubiquitin ligase adaptor for turnover of a diverse number of proteins involved in key cellular processes from chromatin remodeling, transcriptional regulation to cell signaling. Genomic analysis revealed that SPOP somatic mutations are found in a subset of endometrial cancers, suggesting that these mutations act as oncogenic drivers of this gynecologic malignancy. These studies also raise the question as to the role of wild type SPOP in normal uterine function. To address this question, we generated a mouse model (Spopd/d) in which SPOP is ablated in uterine cells that express the PGR...
March 13, 2018: Biology of Reproduction
Haiyan Qin, Guang Zhang, Lianbo Zhang
Polycomb group genes (PcG) encode chromatin modification proteins that are involved in the epigenetic regulation of cell differentiation, proliferation and the aging processes. The key subunit of the PcG complex, enhancer of zeste 2 polycomb repressive complex 2 subunit (EZH2), has a central role in a variety of mechanisms, such as the formation of chromatin structure, gene expression regulation and DNA damage. In the present study, ultraviolet A (UVA) was used to radiate human dermal fibroblasts in order to construct a photo-aged cell model...
April 2018: Experimental and Therapeutic Medicine
Xingting Liu, Xin Lin, Yuling Mi, Jian Li, Caiqiao Zhang
Oxidative stress is an important inducement in ovarian aging which results in fecundity decline in human and diverse animals. As a potent antioxidant, grape seed proanthocyanidin extract (GSPE) was investigated to ameliorate chicken ovarian aging in this study. Firstly, ovarian antioxidant capacity of hens at different ages (90, 150, 280, and 580 days old) was compared to elucidate its age-related changes. Subsequently, a D-gal-induced (2.5 mg/mL) aging ovarian model was established and the cultured ovarian tissues were treated with GSPE at 5  μ g/mL for 72 h to evaluate the putative attenuating effects of GSPE on ovarian aging...
2018: Oxidative Medicine and Cellular Longevity
Warren Winick-Ng, R Jane Rylett
Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by synapse dysfunction and cognitive impairment. Understanding the development and progression of AD is challenging, as the disease is highly complex and multifactorial. Both environmental and genetic factors play a role in AD pathogenesis, highlighted by observations of complex DNA modifications at the single gene level, and by new evidence that also implicates changes in genome architecture in AD patients. The four-dimensional structure of chromatin in space and time is essential for context-dependent regulation of gene expression in post-mitotic neurons...
2018: Frontiers in Molecular Neuroscience
Sun-Ju Yi, Kyunghwan Kim
Chromatin is an intelligent building block that can express either external or internal needs through structural changes. To date, three methods to change chromatin structure and regulate gene expression have been well-documented: histone modification, histone exchange, and ATP-dependent chromatin remodeling. Recently, a growing body of literature has suggested that histone tail cleavage is related to various cellular processes including stem cell differentiation, osteoclast differentiation, granulocyte differentiation, mammary gland differentiation, viral infection, aging, and yeast sporulation...
March 15, 2018: BMB Reports
Jin-Chun Lu, Jun Jing, Li Chen, Yi-Feng Ge, Rui-Xiang Feng, Yuan-Jiao Liang, Bing Yao
BACKGROUND: Many factors may lead to sperm DNA damage. However, it is little known that the correlations of sperm DNA damage with obesity-associated markers, and reproductive hormones and lipids levels in serum and seminal plasma. METHODS: In our prospective study, a total of 1 010 subfertile men, aged from 18 to 50 years old, were enrolled from August 2012 through June 2015. Their obesity-associated markers, semen parameters, sperm acrosomal enzyme activity, seminal plasma biochemical markers, and reproductive hormones and lipids levels in serum and seminal plasma were detected...
March 14, 2018: Reproductive Biology and Endocrinology: RB&E
Raffaella Nativio, Greg Donahue, Amit Berson, Yemin Lan, Alexandre Amlie-Wolf, Ferit Tuzer, Jon B Toledo, Sager J Gosai, Brian D Gregory, Claudio Torres, John Q Trojanowski, Li-San Wang, F Brad Johnson, Nancy M Bonini, Shelley L Berger
Aging is the strongest risk factor for Alzheimer's disease (AD), although the underlying mechanisms remain unclear. The chromatin state, in particular through the mark H4K16ac, has been implicated in aging and thus may play a pivotal role in age-associated neurodegeneration. Here we compare the genome-wide enrichment of H4K16ac in the lateral temporal lobe of AD individuals against both younger and elderly cognitively normal controls. We found that while normal aging leads to H4K16ac enrichment, AD entails dramatic losses of H4K16ac in the proximity of genes linked to aging and AD...
March 5, 2018: Nature Neuroscience
Raúl F Pérez, Juan Ramón Tejedor, Gustavo F Bayón, Agustín F Fernández, Mario F Fraga
Cancer is an aging-associated disease, but the underlying molecular links between these processes are still largely unknown. Gene promoters that become hypermethylated in aging and cancer share a common chromatin signature in ES cells. In addition, there is also global DNA hypomethylation in both processes. However, the similarity of the regions where this loss of DNA methylation occurs is currently not well characterized, and it is unknown if such regions also share a common chromatin signature in aging and cancer...
March 5, 2018: Aging Cell
B D Adkins, A B Barlow, A Jack, S J Schultenover, M M Desouki, A C Coogan, V L Weiss
INTRODUCTION: The characteristic features of Papanicolaou (Pap) tests collected from female-to-male (FTM) transgender patients on androgen therapy have not been well defined in the literature. FTM transgender patients require cervical cancer screening with the same recommended frequency as cis-gender females. Dysplasia remains challenging to differentiate from atrophy. Without pertinent history, the atrophic findings in younger transgender patients can be misinterpreted as high-grade dysplasia...
February 28, 2018: Cytopathology: Official Journal of the British Society for Clinical Cytology
Li Zhang, Cuiping Wang, Shuangni Yu, Congwei Jia, Jie Yan, Zhaohui Lu, Jie Chen
Mutations in the AT-rich interactive domain 1A gene, which encodes a subunit of the Switch/Sucrose nonfermentable chromatin remodeling complex, can result in loss of protein expression and are associated with different cancers. Here, we used immunohistochemistry to investigate the significance of AT-rich interactive domain 1A loss in 73 pancreatic ductal adenocarcinoma cases with paired paracancerous normal pancreatic tissues. The relationship between levels of the AT-rich interactive domain 1A protein product, BAF250a, and clinicopathological parameters in the 73 pancreatic cancer specimens was also analyzed...
January 1, 2018: Technology in Cancer Research & Treatment
Holly Whitton, Larry N Singh, Marissa A Patrick, Andrew J Price, Fernando G Osorio, Carlos López-Otín, Irina M Bochkis
Increasing evidence suggests that regulation of heterochromatin at the nuclear envelope underlies metabolic disease susceptibility and age-dependent metabolic changes, but the mechanism is unknown. Here, we profile lamina-associated domains (LADs) using lamin B1 ChIP-Seq in young and old hepatocytes and find that, although lamin B1 resides at a large fraction of domains at both ages, a third of lamin B1-associated regions are bound exclusively at each age in vivo. Regions occupied by lamin B1 solely in young livers are enriched for the forkhead motif, bound by Foxa pioneer factors...
February 27, 2018: Aging Cell
Miriam G Jasiulionis
Epigenetics refers to the study of mechanisms controlling the chromatin structure, which has fundamental role in the regulation of gene expression and genome stability. Epigenetic marks, such as DNA methylation and histone modifications, are established during embryonic development and epigenetic profiles are stably inherited during mitosis, ensuring cell differentiation and fate. Under the effect of intrinsic and extrinsic factors, such as metabolic profile, hormones, nutrition, drugs, smoke, and stress, epigenetic marks are actively modulated...
2018: Frontiers in Immunology
Michela Manni, Sanjay Gupta, Edd Ricker, Yurii Chinenov, Sung Ho Park, Man Shi, Tania Pannellini, Rolf Jessberger, Lionel B Ivashkiv, Alessandra B Pernis
Age-associated B cells (ABCs) are a subset of B cells dependent on the transcription factor T-bet that accumulate prematurely in autoimmune settings. The pathways that regulate ABCs in autoimmunity are largely unknown. SWAP-70 and DEF6 (also known as IBP or SLAT) are the only two members of the SWEF family, a unique family of Rho GTPase-regulatory proteins that control both cytoskeletal dynamics and the activity of the transcription factor IRF4. Notably, DEF6 is a newly identified human risk variant for systemic lupus erythematosus...
February 26, 2018: Nature Immunology
Hong-Qun Wang, Li Jie, Huai-Yin Shi
BACKGROUND: Low-grade malignant endolymphatic sac tumor (ELST) is a rare neoplasm, occurring in the inner ear and invading the temporal bone. This study aims to investigate the clinicopathological features of low-grade malignant ELSTs. METHODS: The clinicopathological data of 21 patients with low-grade malignant ELSTs were collected and analyzed. RESULTS: The patients were aged 16-71 years, with an average age of 40.3 years and a median age of 39 years, and the male to female ratio was 1:1...
December 14, 2017: Pathology, Research and Practice
Joon Tae Park, Hyun Tae Kang, Chi Hyun Park, Young-Sam Lee, Kyung A Cho, Sang Chul Park
In our previous study, we uncovered a novel mechanism in which amelioration of Hutchinson-Gilford progeria syndrome (HGPS) phenotype is mediated by mitochondrial functional recovery upon rho-associated protein kinase (ROCK) inhibition. However, it remains elusive whether this mechanism is also applied to the amelioration of normal aging cells. In this study, we used Y-27632 and fasudil as effective ROCK inhibitors, and examined their role in senescence. We found that ROCK inhibition induced the functional recovery of the mitochondria as well as the metabolic reprogramming, which are two salient features that are altered in normal aging cells...
February 20, 2018: Experimental Gerontology
Miriam Sjåstad Langseth, Trine Baur Opstad, Vibeke Bratseth, Svein Solheim, Harald Arnesen, Alf Åge Pettersen, Ingebjørg Seljeflot, Ragnhild Helseth
Background Neutrophil extracellular traps, comprising chromatin and granule proteins, have been implicated in atherothrombosis. Design and methods We investigated whether the circulating neutrophil extracellular traps markers, double-stranded DNA and myeloperoxidase-DNA were associated with clinical outcome and hypercoagulability in patients with stable coronary artery disease. Patients with angiographically verified stable coronary artery disease ( n = 1001) were included. Follow-up was 2 years, recording 106 clinical endpoints (unstable angina, non-haemorrhagic stroke, myocardial infarction or death)...
January 1, 2018: European Journal of Preventive Cardiology
Bruce H Howard, Tazuko H Hirai, Valya R Russanova
Substantial evidence has accumulated linking epigenome change to alterations in stem cell function during postnatal development and aging. Yet much remains to be learned about causal relationships, and large gaps remain in our understanding of epigenome-transcriptome interactions. Here we investigate structural features of large histone H3K27me3-enriched regions in human stem cell-like monocytes and their dendritic cell derivatives, where the H3K27me3 modification is considered to demarcate Polycomb (PcG) domains...
2018: PloS One
Uri Kahanovitch, Vishnu A Cuddapah, Natasha L Pacheco, Leanne M Holt, Daniel K Mulkey, Alan K Percy, Michelle L Olsen
Rett syndrome (RTT) is an X-linked neurodevelopmental disorder usually caused by mutations in methyl-CpG-binding protein 2 (MeCP2). RTT is typified by apparently normal development until 6-18 mo of age, when motor and communicative skills regress and hand stereotypies, autonomic symptoms, and seizures present. Restoration of MeCP2 function selectively to astrocytes reversed several deficits in a murine model of RTT, but the mechanism of this rescue is unknown. Astrocytes carry out many essential functions required for normal brain functioning, including extracellular K+ buffering...
January 2018: ENeuro
Katie L Bales, Lara Ianov, Andrew J Kennedy, J David Sweatt, Alecia K Gross
Purpose: Epigenetic and transcriptional mechanisms have been shown to contribute to long-lasting functional changes in adult neurons. The purpose of this study was to identify any such modifications in diseased retinal tissues from a mouse model of rhodopsin mutation-associated autosomal dominant retinitis pigmentosa (ADRP), Q344X, relative to age-matched wild-type (WT) controls. Methods: We performed RNA sequencing (RNA-seq) at poly(A) selected RNA to profile the transcriptional patterns in 3-week-old ADRP mouse model rhodopsin Q344X compared to WT controls...
2018: Molecular Vision
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