Epigenetic enzymes: A role in aging and prospects for pharmacological targeting

Pasyukova, Elena G.; Symonenko, Alexander V.; Rybina, Olga Y.; Vaiserman, Alexander

doi:10.1016/j.arr.2021.101312

Cited by 18 publications

(12 citation statements)

References 320 publications

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“…During BMSC senescence, DNA methylations are reduced in the whole genome [ 28 ]. Meanwhile, inhibitory histone modifications such as H3 Lys9 trimethylation and H4 Lys20 trimethylation are also reduced [ 29 ].…”

Section: Main Textmentioning

confidence: 99%

“…DNA methylation is catalyzed and maintained by the DNA methyltransferase (DNMT) family. DNMTs in mammals are divided into two families: DNMT1 and DNMT3 (DNMT2, mainly methyltransferase of tRNA) [ 28 ]. DNMT3 includes two methyltransferases DNMT3a, DNMT3b, and a regulatory protein DNMT3L.…”

Section: Main Textmentioning

confidence: 99%

“…Ten-eleven translocation (TET) protein catalyzes DNA demethylases, which converts s5-methylcytosine (5-mC) to 5-hydroxymethylcytosine (5-hmC) as an intermediate step for removing methylation markers [ 25 ]. TET protein family includes TET1, TET2, and TET3 [ 28 ]. TET1 is an indirect regulator of osteogenesis and adipogenesis of BMSC, which probably works via recruiting other epigenetic modifiers such as SIN3A and EZH2.…”

Section: Main Textmentioning

confidence: 99%

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Epigenetic therapy targeting bone marrow mesenchymal stem cells for age-related bone diseases

Zhao

Qiu

et al. 2022

Stem Cell Res Ther

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As global aging accelerates, the prevention and treatment of age-related bone diseases are becoming a critical issue. In the process of senescence, bone marrow mesenchymal stem cells (BMSCs) gradually lose the capability of self-renewal and functional differentiation, resulting in impairment of bone tissue regeneration and disorder of bone tissue homeostasis. Alteration in epigenetic modification is an essential factor of BMSC dysfunction during aging. Its transferability and reversibility provide the possibility to combat BMSC aging by reversing age-related modifications. Emerging evidence demonstrates that epigenetic therapy based on aberrant epigenetic modifications could alleviate the senescence and dysfunction of stem cells. This review summarizes potential therapeutic targets for BMSC aging, introduces some potential approaches to alleviating BMSC aging, and analyzes its prospect in the clinical application of age-related bone diseases.

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Section: Main Textmentioning

confidence: 99%

Section: Main Textmentioning

confidence: 99%

Section: Main Textmentioning

confidence: 99%

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Epigenetic therapy targeting bone marrow mesenchymal stem cells for age-related bone diseases

Zhao

Qiu

et al. 2022

Stem Cell Res Ther

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“…Epigenetic regulation plays an important role in anticancer therapeutics and is an attractive basis for rational drug design. 102,103 The epigenetic readers, BET proteins, regulate the expression of several genes and pathways associated with acute myeloid leukaemia, acute lymphoblastic leukaemia, multiple myeloma, and non-Hodgkin's lymphoma. 104 NHWD-870, which targets BET proteins, significantly reduces tumour size and suppresses tumour growth.…”

Section: Discussionmentioning

confidence: 99%

The binding mechanism of NHWD-870 to bromodomain-containing protein 4 based on molecular dynamics simulations and free energy calculation

Shi

Weng

et al. 2022

Phys. Chem. Chem. Phys.

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“…Since Hcy is involved in the methionine cycle by using as a methyl group carrier, in which the methyl group of Hcy is transferred to not only DNA but also histones and other proteins, the presence of methyl group at a specific CpG dinucleotide site may directly prevent DNA from recognizing and binding to transcription factors (Lai et al, 2020 ). Furthermore, methylated DNA can prevent the binding of HDACs, which can catalyze histone modification and form chromatin‐remodeling complexes, leading to altered structure of chromatin and transcription repression (Pasyukova et al, 2021 ). Epigenetic regulation on transcription is initiated by specific transcription factors that bind to the promoters of genes upon altering transcription.…”

Section: Discussionmentioning

confidence: 99%

miR‐195‐3p alleviates homocysteine‐mediated atherosclerosis by targeting IL‐31 through its epigenetics modifications

Xiong

Ding

et al. 2021

Aging Cell

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Atherosclerosis is a serious age‐related disease, which has a tremendous impact on health care globally. Macrophage inflammation is crucial for the initiation and progression of atherosclerosis, and microRNAs (miRNAs) recently have emerged as potent modulators of inflammation, while the underlying mechanisms of its involvement in homocysteine (Hcy)‐mediated macrophage inflammation of atherosclerosis remain largely unknown. Here, we demonstrated that elevated Hcy inhibits the expression of miR‐195‐3p, which in turn enhances IL‐31 expression and thereby causes the secretion of macrophages pro‐inflammatory factors IL‐1β, IL‐6 and TNF‐α and accelerate atherosclerosis. Furthermore, we identified that Hcy can induce DNA hypermethylation and H3K9 deacetylation of miR‐195‐3p promoter due to the increased the binding of DNMT3a and HDAC11 at its promoter. More importantly, Sp1 interacts with DNMT3a suppressed the binding of HDAC11 at miR‐195‐3p promoter and promoted its transcription. In summary, our results revealed a novel mechanism that transcriptional and epigenetic regulation of miR‐195‐3p inhibits macrophage inflammation through targeting IL‐31, which provides a candidate diagnostic marker and novel therapeutic target in cardiovascular diseases induced by Hcy.

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Epigenetic enzymes: A role in aging and prospects for pharmacological targeting

Cited by 18 publications

References 320 publications

Epigenetic therapy targeting bone marrow mesenchymal stem cells for age-related bone diseases

Epigenetic therapy targeting bone marrow mesenchymal stem cells for age-related bone diseases

The binding mechanism of NHWD-870 to bromodomain-containing protein 4 based on molecular dynamics simulations and free energy calculation

miR‐195‐3p alleviates homocysteine‐mediated atherosclerosis by targeting IL‐31 through its epigenetics modifications

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