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      Oocyte Aging: A Multifactorial Phenomenon in A Unique Cell

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          Abstract

          The oocyte is considered to be the largest cell in mammalian species. Women hoping to become pregnant face a ticking biological clock. This is becoming increasingly challenging as an increase in life expectancy is accompanied by the tendency to conceive at older ages. With advancing maternal age, the fertilized egg will exhibit lower quality and developmental competence, which contributes to increased chances of miscarriage due to several causes such as aneuploidy, oxidative stress, epigenetics, or metabolic disorders. In particular, heterochromatin in oocytes and with it, the DNA methylation landscape undergoes changes. Further, obesity is a well-known and ever-increasing global problem as it is associated with several metabolic disorders. More importantly, both obesity and aging negatively affect female reproduction. However, among women, there is immense variability in age-related decline of oocytes’ quantity, developmental competence, or quality. Herein, the relevance of obesity and DNA-methylation will be discussed as these aspects have a tremendous effect on female fertility, and it is a topic of continuous and widespread interest that has yet to be fully addressed for the mammalian oocyte.

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          Most cited references141

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          The Hallmarks of Aging

          Aging is characterized by a progressive loss of physiological integrity, leading to impaired function and increased vulnerability to death. This deterioration is the primary risk factor for major human pathologies, including cancer, diabetes, cardiovascular disorders, and neurodegenerative diseases. Aging research has experienced an unprecedented advance over recent years, particularly with the discovery that the rate of aging is controlled, at least to some extent, by genetic pathways and biochemical processes conserved in evolution. This Review enumerates nine tentative hallmarks that represent common denominators of aging in different organisms, with special emphasis on mammalian aging. These hallmarks are: genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, deregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, and altered intercellular communication. A major challenge is to dissect the interconnectedness between the candidate hallmarks and their relative contributions to aging, with the final goal of identifying pharmaceutical targets to improve human health during aging, with minimal side effects. Copyright © 2013 Elsevier Inc. All rights reserved.
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            N6-Methyladenosine in Nuclear RNA is a Major Substrate of the Obesity-Associated FTO

            We report here that FTO (fat mass and obesity-associated protein) exhibits efficient oxidative demethylation activity of abundant N 6-methyladenosine (m6A) residues in RNA in vitro. FTO knockdown with siRNA led to an increased level of m6A in mRNA, whereas overexpression of FTO resulted in a decreased level of m6A in human cells. We further show that FTO partially colocalizes with nuclear speckles, supporting m6A in nuclear RNA as a physiological substrate of FTO.
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              Dynamic RNA Modifications in Gene Expression Regulation

              Over 100 types of chemical modifications have been identified in cellular RNAs. While the 5' cap modification and the poly(A) tail of eukaryotic mRNA play key roles in regulation, internal modifications are gaining attention for their roles in mRNA metabolism. The most abundant internal mRNA modification is N6-methyladenosine (m6A), and identification of proteins that install, recognize, and remove this and other marks have revealed roles for mRNA modification in nearly every aspect of the mRNA life cycle, as well as in various cellular, developmental, and disease processes. Abundant noncoding RNAs such as tRNAs, rRNAs, and spliceosomal RNAs are also heavily modified and depend on the modifications for their biogenesis and function. Our understanding of the biological contributions of these different chemical modifications is beginning to take shape, but it's clear that in both coding and noncoding RNAs, dynamic modifications represent a new layer of control of genetic information.
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                Author and article information

                Journal
                Aging Dis
                Aging Dis
                Aging and Disease
                JKL International LLC
                2152-5250
                1 February 2024
                1 February 2024
                : 15
                : 1
                : 5-21
                Affiliations
                [1-ad-15-1-5] 1Department of Preclinical and Basic Sciences, Faculty of Biological and Veterinary Sciences, Nicolaus Copernicus University, Torun, Poland.
                [2-ad-15-1-5] 2Department of Human Genetics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.
                [3-ad-15-1-5] 3Altos Labs, San Diego, CA, USA.
                [4-ad-15-1-5] 4Institute of Biomedical and Oral Research, Hebrew University of Jerusalem, Jerusalem, Israel
                Author notes
                [* ]Correspondence should be addressed to: Dr. Paweł Kordowitzki, Department of Basic and Preclinical Sciences, Faculty of Biological and Veterinary Sciences, Nicolaus Copernicus University, Torun, Poland. email: p.kordowitzki@ 123456umk.pl.
                Article
                ad-15-1-5
                10.14336/AD.2023.0527
                10796106
                37307833
                2c15e63e-a16b-4677-9e82-1776fc4a3c05
                Copyright: © 2024 Kordowitzki et al.

                this is an open access article distributed under the terms of the creative commons attribution license, which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.

                History
                : 6 May 2023
                : 26 May 2023
                : 27 May 2023
                Funding
                Funded by: IDUB Debiuty
                Award ID: 4101.00000066
                We want to thank Norbert Gleicher and David Albertini for their critical comments during the writing of this article. Figures have been created with biorender.com, access date 03.09.2022. This work was supported by the IDUB Debiuty grant [Nr. 4101.00000066].
                Categories
                Review

                aging,methylome,dna-methylation,epigenetics,heterochromatin,oocyte,egg,er stress,protein folding,fibrosis,stella,tet3,uhrf1

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