Nuclear Organization in Stress and Aging

Romero-Bueno, Raquel; Ruiz, Patricia de la Cruz; Artal‐Sanz, Marta; Askjaer, Peter; Dobrzynska, Agnieszka

doi:10.3390/cells8070664

Cited by 29 publications

(22 citation statements)

References 183 publications

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“…A decrease in the amount of lamin B1, the accumulation of toxic levels of prelamin A and the expression of progerin (the pathogenic form of lamin A) lead to defects in the structure of the nucleus and are associated with cellular senescence and an organism aging [ 2 , 88 , 89 ]. Mutations in genes of a nuclear lamina cause premature aging syndromes called laminopathies (including Hutchinson–Gilford syndrome) [ 90 , 91 ]. It affects the speed of telomere shortening, the activity of genes and signaling pathways (including those associated with DNA damage response and aging), the organization of chromatin, and DNA methylation patterns [ 2 , 89 ].…”

Section: Impairment Of the Mechanisms For Maintaining Genome Stabimentioning

confidence: 99%

Genome-Protecting Compounds as Potential Geroprotectors

Proshkina

Shaposhnikov

Moskalev

2020

IJMS

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Throughout life, organisms are exposed to various exogenous and endogenous factors that cause DNA damages and somatic mutations provoking genomic instability. At a young age, compensatory mechanisms of genome protection are activated to prevent phenotypic and functional changes. However, the increasing stress and age-related deterioration in the functioning of these mechanisms result in damage accumulation, overcoming the functional threshold. This leads to aging and the development of age-related diseases. There are several ways to counteract these changes: (1) prevention of DNA damage through stimulation of antioxidant and detoxification systems, as well as transition metal chelation; (2) regulation of DNA methylation, chromatin structure, non-coding RNA activity and prevention of nuclear architecture alterations; (3) improving DNA damage response and repair; (4) selective removal of damaged non-functional and senescent cells. In the article, we have reviewed data about the effects of various trace elements, vitamins, polyphenols, terpenes, and other phytochemicals, as well as a number of synthetic pharmacological substances in these ways. Most of the compounds demonstrate the geroprotective potential and increase the lifespan in model organisms. However, their genome-protecting effects are non-selective and often are conditioned by hormesis. Consequently, the development of selective drugs targeting genome protection is an advanced direction.

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Section: Impairment Of the Mechanisms For Maintaining Genome Stabimentioning

confidence: 99%

Genome-Protecting Compounds as Potential Geroprotectors

Proshkina

Shaposhnikov

Moskalev

2020

IJMS

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“…For example, POA leads to the incompact cumulus expansion and fragmentation [5], increases the level of reactive oxygen species (ROS) [6,7,8], decreases the expression of anti-apoptotic factor BCL-2 [9] and activates maturation promoting factor (MPF) in oocytes [10,11]. Also, nuclear organization is affected in stress and aging oocytes [12]. All these changes can seriously impair the oocyte quality and subsequent embryo development [13,14], which inevitably affects the ART success.…”

Section: Introductionmentioning

confidence: 99%

Roles of Resveratrol in Improving the Quality of Postovulatory Aging Oocytes In Vitro

Sun

Tang

Shen

et al. 2019

Cells

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After ovulation, mammalian oocytes will undergo a time-dependent process of aging if they are not fertilized. This postovulatory aging (POA) seriously affects the oocyte quality and then impairs the subsequent fertilization and early embryo development, which should be avoided especially in assisted reproductive technology (ART). Resveratrol is an antioxidant substance that can scavenge free radicals and is effective in improving ovary functions. Here, mouse oocytes were used to investigate the effects and mechanisms of resveratrol on POA oocytes in vitro. With 1.0 µM resveratrol treatment during aging process, the rates of fertilization and blastocyst in POA oocytes increased significantly compared with those in the POA group. Resveratrol can reduce the loss of sperm binding sites by stabilizing Juno. Resveratrol can maintain the normal morphology of spindle and mitochondrion distribution and alleviate the levels of ROS and early apoptosis. Additionally, resveratrol can reduce the changes of H3K9me2. Therefore, resveratrol can significantly improve the quality of POA oocytes in vitro to enhance the rates of fertilization and blastocyst, which may be very helpful during the ART process.

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“…Genome-wide studies support the view that DNA methylation has a negative impact on enhancer activity [89,90,91,92]. There is a significant association between the enhancer epigenetic signature, transcription factor binding and enhancer activity at the distal promoter region in neural progenitor cells and embryonic stem cells [55,93,94,95].…”

Section: Effect Of Dna Methylation On Enhancer Activitymentioning

confidence: 95%

Enhancer Dysfunction in 3D Genome and Disease

Xia

Wei

2019

Cells

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Spatiotemporal patterns of gene expression depend on enhancer elements and other factors during individual development and disease progression. The rapid progress of high-throughput techniques has led to well-defined enhancer chromatin properties. Various genome-wide methods have revealed a large number of enhancers and the discovery of three-dimensional (3D) genome architecture showing the distant interacting mechanisms of enhancers that loop to target gene promoters. Whole genome sequencing projects directed at cancer have led to the discovery of substantial enhancer dysfunction in misregulating gene expression and in tumor initiation and progression. Results from genome-wide association studies (GWAS) combined with functional genomics analyses have elucidated the functional impacts of many cancer risk-associated variants that are enriched within the enhancer regions of chromatin. Risk variants dysregulate the expression of enhancer variant-associated genes via 3D genomic interactions. Moreover, these enhancer variants often alter the chromatin binding affinity for cancer-relevant transcription factors, which in turn leads to aberrant expression of the genes associated with cancer susceptibility. In this review, we investigate the extent to which these genetic regulatory circuits affect cancer predisposition and how the recent development of genome-editing methods have enabled the determination of the impacts of genomic variation and alteration on cancer phenotype, which will eventually lead to better management plans and treatment responses to human cancer in the clinic.

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Nuclear Organization in Stress and Aging

Cited by 29 publications

References 183 publications

Genome-Protecting Compounds as Potential Geroprotectors

Genome-Protecting Compounds as Potential Geroprotectors

Roles of Resveratrol in Improving the Quality of Postovulatory Aging Oocytes In Vitro

Enhancer Dysfunction in 3D Genome and Disease

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