{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T03:41:02Z","timestamp":1793245262272,"version":"4.5.0"},"reference-count":93,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2021,3,1]],"date-time":"2021-03-01T00:00:00Z","timestamp":1614556800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2021,3,1]],"date-time":"2021-03-01T00:00:00Z","timestamp":1614556800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"}],"funder":[{"DOI":"10.13039\/100005366","name":"American Foundation for Aging Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005366","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002322","name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002322","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Mechanisms of Ageing and Development"],"published-print":{"date-parts":[[2021,3]]},"DOI":"10.1016\/j.mad.2020.111425","type":"journal-article","created":{"date-parts":[[2020,12,28]],"date-time":"2020-12-28T01:53:44Z","timestamp":1609120424000},"page":"111425","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":103,"special_numbering":"C","title":["Cellular hallmarks of aging emerge in the ovary prior to primordial follicle depletion"],"prefix":"10.1016","volume":"194","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4874-3802","authenticated-orcid":false,"given":"Victor A.","family":"Ansere","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6675-9998","authenticated-orcid":false,"given":"Samim","family":"Ali-Mondal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9220-3064","authenticated-orcid":false,"given":"Roshini","family":"Sathiaseelan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Driele N.","family":"Garcia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3168-3188","authenticated-orcid":false,"given":"Jos\u00e9 V.V.","family":"Isola","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00e9ssica D.","family":"Henseb","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5328-4922","authenticated-orcid":false,"given":"Tatiana D.","family":"Saccon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah R.","family":"Oca\u00f1as","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7484-0991","authenticated-orcid":false,"given":"Kyla B.","family":"Tooley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9996-9123","authenticated-orcid":false,"given":"Michael B.","family":"Stout","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3410-2860","authenticated-orcid":false,"given":"Augusto","family":"Schneider","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7027-999X","authenticated-orcid":false,"given":"Willard M.","family":"Freeman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.mad.2020.111425_bib0005","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1093\/humupd\/dmn063","article-title":"The current knowledge on radiosensitivity of ovarian follicle development stages","volume":"15","author":"Adriaens","year":"2009","journal-title":"Hum. Reprod. Update"},{"key":"10.1016\/j.mad.2020.111425_bib0010","doi-asserted-by":"crossref","first-page":"R106","DOI":"10.1186\/gb-2010-11-10-r106","article-title":"Differential expression analysis for sequence count data","volume":"11","author":"Anders","year":"2010","journal-title":"Genome Biol."},{"key":"10.1016\/j.mad.2020.111425_bib0015","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/0028-2243(74)90006-9","article-title":"The endocrinology of ovarian steroid secretion","volume":"4","author":"Baird","year":"1974","journal-title":"Eur. J. Obstet. Gynecol. Reprod. Biol."},{"key":"10.1016\/j.mad.2020.111425_bib0020","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1098\/rspb.1963.0055","article-title":"A quantitative and cytological study of germ cells in human ovaries","volume":"158","author":"Baker","year":"1963","journal-title":"Proc. R. Soc. Lond., B, Biol. Sci."},{"key":"10.1016\/j.mad.2020.111425_bib0025","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1038\/nature10600","article-title":"Clearance of p16 Ink4a-positive senescent cells delays ageing-associated disorders","volume":"479","author":"Baker","year":"2011","journal-title":"Nature"},{"key":"10.1016\/j.mad.2020.111425_bib0030","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1007\/s00439-011-1011-z","article-title":"Genes that escape from X inactivation","volume":"130","author":"Berletch","year":"2011","journal-title":"Hum. Genet."},{"key":"10.1016\/j.mad.2020.111425_bib0035","doi-asserted-by":"crossref","first-page":"728","DOI":"10.1016\/j.molcel.2016.05.013","article-title":"The aging epigenome","volume":"62","author":"Booth","year":"2016","journal-title":"Mol. Cell"},{"key":"10.1016\/j.mad.2020.111425_bib0040","doi-asserted-by":"crossref","first-page":"934","DOI":"10.1126\/science.1220671","article-title":"Quantitative sequencing of 5-methylcytosine and 5-hydroxymethylcytosine at single-base resolution","volume":"336","author":"Booth","year":"2012","journal-title":"Science"},{"key":"10.1016\/j.mad.2020.111425_bib0045","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1530\/REP-16-0129","article-title":"Reproductive age-associated fibrosis in the stroma of the mammalian ovary","volume":"152","author":"Briley","year":"2016","journal-title":"Reproduction (Cambridge, England)"},{"key":"10.1016\/j.mad.2020.111425_bib0050","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1210\/er.2009-0006","article-title":"Ovarian aging: mechanisms and clinical consequences","volume":"30","author":"Broekmans","year":"2009","journal-title":"Endocr. Rev."},{"key":"10.1016\/j.mad.2020.111425_bib0055","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1016\/0092-8674(80)90305-0","article-title":"Transposable elements","volume":"20","author":"Calos","year":"1980","journal-title":"Cell"},{"key":"10.1016\/j.mad.2020.111425_bib0060","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1016\/j.fertnstert.2008.10.049","article-title":"Infertility service use among U.S. women: 1995 and 2002","volume":"93","author":"Chandra","year":"2010","journal-title":"Fertil. Steril."},{"key":"10.1016\/j.mad.2020.111425_bib0065","first-page":"237","article-title":"Effect of aging on 5-hydroxymethylcytosine in the mouse hippocampus","volume":"30","author":"Chen","year":"2012","journal-title":"Restor. Neurol. Neurosci."},{"key":"10.1016\/j.mad.2020.111425_bib0070","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1095\/biolreprod.111.094367","article-title":"Meiotic origins of maternal age-related aneuploidy","volume":"86","author":"Chiang","year":"2012","journal-title":"Biol. Reprod."},{"key":"10.1016\/j.mad.2020.111425_bib0075","doi-asserted-by":"crossref","first-page":"1672","DOI":"10.1016\/j.neurobiolaging.2011.06.003","article-title":"Prevention of age-related changes in hippocampal levels of 5-methylcytidine by caloric restriction","volume":"33","author":"Chouliaras","year":"2012","journal-title":"Neurobiol. Aging"},{"key":"10.1016\/j.mad.2020.111425_bib0080","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1007\/s11357-019-00090-2","article-title":"Tamoxifen induction of Cre recombinase does not cause long-lasting or sexually divergent responses in the CNS epigenome or transcriptome: implications for the design of aging studies","volume":"41","author":"Chucair-Elliott","year":"2019","journal-title":"Geroscience"},{"key":"10.1016\/j.mad.2020.111425_bib0085","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1038\/s42003-020-01418-x","article-title":"Inducible cell-specific mouse models for paired epigenetic and transcriptomic studies of microglia and astroglia","volume":"3","author":"Chucair-Elliott","year":"2020","journal-title":"Commun. Biol."},{"key":"10.1016\/j.mad.2020.111425_bib0090","doi-asserted-by":"crossref","first-page":"e1002384","DOI":"10.1371\/journal.pgen.1002384","article-title":"Repetitive elements may comprise over two-thirds of the human genome","volume":"7","author":"de Koning","year":"2011","journal-title":"PLoS Genet."},{"key":"10.1016\/j.mad.2020.111425_bib0095","doi-asserted-by":"crossref","first-page":"624","DOI":"10.1210\/er.2009-0012","article-title":"The mammalian ovary from genesis to revelation","volume":"30","author":"Edson","year":"2009","journal-title":"Endocr. Rev."},{"key":"10.1016\/j.mad.2020.111425_bib0100","series-title":"Crossover in the Median Age at First Marriage and First Birth: Thirty-Five Years of Change. Family Profiles, FP-17-22","author":"Eickmeyer","year":"2017"},{"key":"10.1016\/j.mad.2020.111425_bib0105","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1007\/978-1-4939-6670-7_10","article-title":"The specific histochemical stain for lipofuscin: a novel method to detect senescent cells","volume":"1534","author":"Evangelou","year":"2017","journal-title":"Methods Mol. Biol."},{"key":"10.1016\/j.mad.2020.111425_bib0110","doi-asserted-by":"crossref","first-page":"1342","DOI":"10.1093\/oxfordjournals.humrep.a137570","article-title":"Accelerated disappearance of ovarian follicles in mid-life: implications for forecasting menopause","volume":"7","author":"Faddy","year":"1992","journal-title":"Hum. Reprod."},{"key":"10.1016\/j.mad.2020.111425_bib0115","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1186\/s13072-017-0133-5","article-title":"Transcription and chromatin determinants of de novo DNA methylation timing in oocytes","volume":"10","author":"Gahurova","year":"2017","journal-title":"Epigenetics Chromatin"},{"key":"10.1016\/j.mad.2020.111425_bib0120","doi-asserted-by":"crossref","first-page":"37","DOI":"10.18632\/aging.100527","article-title":"Specific lipofuscin staining as a novel biomarker to detect replicative and stress-induced senescence. A method applicable in cryo-preserved and archival tissues","volume":"5","author":"Georgakopoulou","year":"2013","journal-title":"Aging (Albany NY)"},{"key":"10.1016\/j.mad.2020.111425_bib0125","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1186\/s13072-016-0080-6","article-title":"Absence of genomic hypomethylation or regulation of cytosine-modifying enzymes with aging in male and female mice","volume":"9","author":"Hadad","year":"2016","journal-title":"Epigenetics Chromatin"},{"key":"10.1016\/j.mad.2020.111425_bib0130","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1146\/annurev-genom-090413-025437","article-title":"Non-CG methylation in the human genome","volume":"16","author":"He","year":"2015","journal-title":"Annu. Rev. Genomics Hum. Genet."},{"key":"10.1016\/j.mad.2020.111425_bib0135","doi-asserted-by":"crossref","first-page":"2652","DOI":"10.1016\/j.cub.2017.07.033","article-title":"Unmasking transcriptional heterogeneity in senescent cells","volume":"27","author":"Hernandez-Segura","year":"2017","journal-title":"Curr. Biol."},{"key":"10.1016\/j.mad.2020.111425_bib0140","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1016\/j.tcb.2018.02.001","article-title":"Hallmarks of cellular senescence","volume":"28","author":"Hernandez-Segura","year":"2018","journal-title":"Trends Cell Biol."},{"key":"10.1016\/j.mad.2020.111425_bib0145","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1016\/j.rbmo.2015.03.001","article-title":"Altered amphiregulin expression induced by diverse luteinizing hormone receptor reactivity in granulosa cells affects IVF outcomes","volume":"30","author":"Huang","year":"2015","journal-title":"Reprod. Biomed. Online"},{"key":"10.1016\/j.mad.2020.111425_bib0150","doi-asserted-by":"crossref","first-page":"1068","DOI":"10.1126\/science.1063852","article-title":"The role of DNA methylation in mammalian epigenetics","volume":"293","author":"Jones","year":"2001","journal-title":"Science"},{"key":"10.1016\/j.mad.2020.111425_bib0155","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1196\/annals.1404.008","article-title":"Lipofuscin: formation, distribution, and metabolic consequences","volume":"1119","author":"Jung","year":"2007","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"10.1016\/j.mad.2020.111425_bib0160","doi-asserted-by":"crossref","first-page":"3228","DOI":"10.1210\/en.2005-1588","article-title":"Serum anti-mullerian hormone levels reflect the size of the primordial follicle pool in mice","volume":"147","author":"Kevenaar","year":"2006","journal-title":"Endocrinology"},{"key":"10.1016\/j.mad.2020.111425_bib0165","doi-asserted-by":"crossref","first-page":"380","DOI":"10.3346\/jkms.2000.15.4.380","article-title":"Influence of menopause on high density lipoprotein-cholesterol and lipids","volume":"15","author":"Kim","year":"2000","journal-title":"J. Korean Med. Sci."},{"key":"10.1016\/j.mad.2020.111425_bib0170","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/0027-5107(82)90191-9","article-title":"Induction of congenital anomalies in offspring of female mice exposed to varying doses of X-rays","volume":"106","author":"Kirk","year":"1982","journal-title":"Mutat. Res."},{"key":"10.1016\/j.mad.2020.111425_bib0175","doi-asserted-by":"crossref","first-page":"2697","DOI":"10.4161\/cc.5.23.3510","article-title":"Senescence, wound healing, and cancer: the PAI-1 connection","volume":"5","author":"Kortlever","year":"2006","journal-title":"Cell Cycle"},{"key":"10.1016\/j.mad.2020.111425_bib0180","doi-asserted-by":"crossref","first-page":"877","DOI":"10.1038\/ncb1448","article-title":"Plasminogen activator inhibitor-1 is a critical downstream target of p53 in the induction of replicative senescence","volume":"8","author":"Kortlever","year":"2006","journal-title":"Nat. Cell Biol."},{"key":"10.1016\/j.mad.2020.111425_bib0185","doi-asserted-by":"crossref","first-page":"929","DOI":"10.1126\/science.1169786","article-title":"The nuclear DNA base 5-hydroxymethylcytosine is present in Purkinje neurons and the brain","volume":"324","author":"Kriaucionis","year":"2009","journal-title":"Science"},{"key":"10.1016\/j.mad.2020.111425_bib0190","doi-asserted-by":"crossref","first-page":"1299","DOI":"10.1172\/JCI22475","article-title":"Ink4a\/Arf expression is a biomarker of aging","volume":"114","author":"Krishnamurthy","year":"2004","journal-title":"J. Clin. Invest."},{"key":"10.1016\/j.mad.2020.111425_bib0195","doi-asserted-by":"crossref","first-page":"3613","DOI":"10.1242\/jcs.113.20.3613","article-title":"Senescence-associated (beta)-galactosidase reflects an increase in lysosomal mass during replicative ageing of human endothelial cells","volume":"113","author":"Kurz","year":"2000","journal-title":"J. Cell. Sci."},{"key":"10.1016\/j.mad.2020.111425_bib0200","doi-asserted-by":"crossref","first-page":"726","DOI":"10.1634\/theoncologist.2011-0050","article-title":"Overweight, obesity, diabetes, and risk of breast cancer: interlocking pieces of the puzzle","volume":"16","author":"La Vecchia","year":"2011","journal-title":"Oncologist"},{"key":"10.1016\/j.mad.2020.111425_bib0205","doi-asserted-by":"crossref","first-page":"127","DOI":"10.5653\/cerm.2012.39.4.127","article-title":"Transcription factors in the maintenance and survival of primordial follicles","volume":"39","author":"Lim","year":"2012","journal-title":"Clin. Exp. Reprod. Med."},{"key":"10.1016\/j.mad.2020.111425_bib0210","doi-asserted-by":"crossref","first-page":"252","DOI":"10.3389\/fnins.2015.00252","article-title":"Turning over DNA methylation in the mind","volume":"9","author":"Lister","year":"2015","journal-title":"Front. Neurosci."},{"key":"10.1016\/j.mad.2020.111425_bib0215","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of relative gene expression data using real-time quantitative PCR and the 2\u2212 \u0394\u0394CT method","volume":"25","author":"Livak","year":"2001","journal-title":"Methods"},{"key":"10.1016\/j.mad.2020.111425_bib0220","doi-asserted-by":"crossref","first-page":"1194","DOI":"10.1016\/j.cell.2013.05.039","article-title":"The hallmarks of aging","volume":"153","author":"L\u00f3pez-Ot\u00edn","year":"2013","journal-title":"Cell"},{"key":"10.1016\/j.mad.2020.111425_bib0225","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1038\/nrg.2017.80","article-title":"The DNA methyltransferase family: a versatile toolkit for epigenetic regulation","volume":"19","author":"Lyko","year":"2018","journal-title":"Nat. Rev. Genet."},{"key":"10.1016\/j.mad.2020.111425_bib0230","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.exger.2016.05.010","article-title":"Keeping the senescence secretome under control: molecular reins on the senescence-associated secretory phenotype","volume":"82","author":"Malaquin","year":"2016","journal-title":"Exp. Gerontol."},{"key":"10.1016\/j.mad.2020.111425_bib0235","doi-asserted-by":"crossref","first-page":"27","DOI":"10.3389\/fnmol.2019.00027","article-title":"Early life stress delays sexual maturation in female mice","volume":"12","author":"Manzano Nieves","year":"2019","journal-title":"Front. Mol. Neurosci."},{"key":"10.1016\/j.mad.2020.111425_bib0240","doi-asserted-by":"crossref","first-page":"1207","DOI":"10.1093\/gerona\/glp134","article-title":"Transplantation of young ovaries to old mice increased life span in transplant recipients","volume":"64","author":"Mason","year":"2009","journal-title":"J. Gerontol. A Biol. Sci. Med. Sci."},{"key":"10.1016\/j.mad.2020.111425_bib0245","doi-asserted-by":"crossref","first-page":"1311","DOI":"10.1093\/gerona\/glu091","article-title":"Hippocampal subregions exhibit both distinct and shared transcriptomic responses to aging and nonneurodegenerative cognitive decline","volume":"69","author":"Masser","year":"2014","journal-title":"J. Gerontol. A Biol. Sci. Med. Sci."},{"key":"10.1016\/j.mad.2020.111425_bib0250","doi-asserted-by":"crossref","first-page":"791","DOI":"10.1530\/rep.1.00793","article-title":"Stops and starts in mammalian oocytes: recent advances in understanding the regulation of meiotic arrest and oocyte maturation","volume":"130","author":"Mehlmann","year":"2005","journal-title":"Reproduction"},{"key":"10.1016\/j.mad.2020.111425_bib0255","doi-asserted-by":"crossref","first-page":"668","DOI":"10.1016\/j.rbmo.2016.09.006","article-title":"Oxidative stress and alterations in DNA methylation: two sides of the same coin in reproduction","volume":"33","author":"Menezo","year":"2016","journal-title":"Reprod. Biomed. Online"},{"key":"10.1016\/j.mad.2020.111425_bib0260","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1038\/npp.2012.112","article-title":"DNA methylation and its basic function","volume":"38","author":"Moore","year":"2013","journal-title":"Neuropsychopharmacology"},{"key":"10.1016\/j.mad.2020.111425_bib0265","doi-asserted-by":"crossref","first-page":"482","DOI":"10.1038\/nrm3823","article-title":"Cellular senescence: from physiology to pathology","volume":"15","author":"Mu\u00f1oz-Esp\u00edn","year":"2014","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"10.1016\/j.mad.2020.111425_bib0270","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1530\/rep.1.00095","article-title":"Methods for quantifying follicular numbers within the mouse ovary","volume":"127","author":"Myers","year":"2004","journal-title":"Reproduction"},{"key":"10.1016\/j.mad.2020.111425_bib0275","doi-asserted-by":"crossref","first-page":"556","DOI":"10.1097\/01.ede.0000165392.35273.d4","article-title":"Age at menopause, cause-specific mortality and total life expectancy","volume":"16","author":"Ossewaarde","year":"2005","journal-title":"Epidemiology"},{"key":"10.1016\/j.mad.2020.111425_bib0280","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/ncomms2861","article-title":"Constitutively active Foxo3 in oocytes preserves ovarian reserve in mice","volume":"4","author":"Pelosi","year":"2013","journal-title":"Nat. Commun."},{"key":"10.1016\/j.mad.2020.111425_bib0285","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1007\/s10577-009-9063-9","article-title":"Dosage compensation and gene expression on the mammalian X chromosome: one plus one does not always equal two","volume":"17","author":"Prothero","year":"2009","journal-title":"Chromosome Res."},{"key":"10.1016\/j.mad.2020.111425_bib0290","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/j.biocel.2015.05.005","article-title":"Dynamic changes of DNA epigenetic marks in mouse oocytes during natural and accelerated aging","volume":"67","author":"Qian","year":"2015","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"10.1016\/j.mad.2020.111425_bib0295","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1101\/gad.276568.115","article-title":"Role of TET enzymes in DNA methylation, development, and cancer","volume":"30","author":"Rasmussen","year":"2016","journal-title":"Genes Dev."},{"key":"10.1016\/j.mad.2020.111425_bib0300","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1083\/jcb.201009094","article-title":"Four faces of cellular senescenceFour faces of senescence","volume":"192","author":"Rodier","year":"2011","journal-title":"J. Cell Biol."},{"key":"10.1016\/j.mad.2020.111425_bib0305","doi-asserted-by":"crossref","first-page":"811","DOI":"10.1016\/j.exger.2011.07.001","article-title":"Transcriptional repression of repeat-derived transcripts correlates with histone hypoacetylation at repetitive DNA elements in aged mice brain","volume":"46","author":"Ryu","year":"2011","journal-title":"Exp. Gerontol."},{"key":"10.1016\/j.mad.2020.111425_bib0310","doi-asserted-by":"crossref","first-page":"110851","DOI":"10.1016\/j.exger.2020.110851","article-title":"Primordial follicle reserve, DNA damage and macrophage infiltration in the ovaries of the long-living Ames dwarf mice","volume":"132","author":"Saccon","year":"2020","journal-title":"Exp. Gerontol."},{"key":"10.1016\/j.mad.2020.111425_bib0315","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1016\/j.mce.2016.09.019","article-title":"Ovarian transcriptome associated with reproductive senescence in the long-living Ames dwarf mice","volume":"439","author":"Schneider","year":"2017","journal-title":"Mol. Cell. Endocrinol."},{"key":"10.1016\/j.mad.2020.111425_bib0320","doi-asserted-by":"crossref","first-page":"622","DOI":"10.1111\/j.1474-9726.2008.00409.x","article-title":"Moderate caloric restriction initiated in rodents during adulthood sustains function of the female reproductive axis into advanced chronological age","volume":"7","author":"Selesniemi","year":"2008","journal-title":"Aging Cell"},{"key":"10.1016\/j.mad.2020.111425_bib0325","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1042\/EBC20190043","article-title":"The role and mechanisms of DNA methylation in the oocyte","volume":"63","author":"Sendzikaite","year":"2019","journal-title":"Essays Biochem."},{"key":"10.1016\/j.mad.2020.111425_bib0330","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1186\/1741-7007-6-24","article-title":"Effects of aging and calorie restriction on the global gene expression profiles of mouse testis and ovary","volume":"6","author":"Sharov","year":"2008","journal-title":"BMC Biol."},{"key":"10.1016\/j.mad.2020.111425_bib0335","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1038\/nrc3960","article-title":"Forging a signature of in vivo senescence","volume":"15","author":"Sharpless","year":"2015","journal-title":"Nat. Rev. Cancer"},{"key":"10.1016\/j.mad.2020.111425_bib0340","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1038\/nmeth.4184","article-title":"Detecting DNA cytosine methylation using nanopore sequencing","volume":"14","author":"Simpson","year":"2017","journal-title":"Nat. Methods"},{"key":"10.1016\/j.mad.2020.111425_bib0345","doi-asserted-by":"crossref","first-page":"811","DOI":"10.1038\/ng.864","article-title":"Dynamic CpG island methylation landscape in oocytes and preimplantation embryos","volume":"43","author":"Smallwood","year":"2011","journal-title":"Nat. Genet."},{"key":"10.1016\/j.mad.2020.111425_bib0350","doi-asserted-by":"crossref","first-page":"743","DOI":"10.1016\/S0959-437X(96)80030-X","article-title":"The origin of interspersed repeats in the human genome","volume":"6","author":"Smit","year":"1996","journal-title":"Curr. Opin. Genet. Dev."},{"key":"10.1016\/j.mad.2020.111425_bib0355","series-title":"Histology, Lipofuscin","author":"Snyder","year":"2020"},{"key":"10.1016\/j.mad.2020.111425_bib0360","doi-asserted-by":"crossref","first-page":"575","DOI":"10.18632\/aging.100681","article-title":"Growth hormone action predicts age-related white adipose tissue dysfunction and senescent cell burden in mice","volume":"6","author":"Stout","year":"2014","journal-title":"Aging (Albany NY)"},{"key":"10.1016\/j.mad.2020.111425_bib0365","doi-asserted-by":"crossref","first-page":"930","DOI":"10.1126\/science.1170116","article-title":"Conversion of 5-methylcytosine to 5-hydroxymethylcytosine in mammalian DNA by MLL partner TET1","volume":"324","author":"Tahiliani","year":"2009","journal-title":"Science"},{"key":"10.1016\/j.mad.2020.111425_bib0370","doi-asserted-by":"crossref","first-page":"966","DOI":"10.1172\/JCI64098","article-title":"Cellular senescence and the senescent secretory phenotype: therapeutic opportunities","volume":"123","author":"Tchkonia","year":"2013","journal-title":"J. Clin. Invest."},{"key":"10.1016\/j.mad.2020.111425_bib0375","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/S0303-7207(98)00171-3","article-title":"Developmental and endocrine aspects of normal ovarian aging","volume":"145","author":"te Velde","year":"1998","journal-title":"Mol. Cell. Endocrinol."},{"key":"10.1016\/j.mad.2020.111425_bib0380","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/S0303-7207(98)00171-3","article-title":"Developmental and endocrine aspects of normal ovarian aging","volume":"145","author":"te Velde","year":"1998","journal-title":"Mol. Cell. Endocrinol."},{"key":"10.1016\/j.mad.2020.111425_bib0385","doi-asserted-by":"crossref","first-page":"172ra21","DOI":"10.1126\/scitranslmed.3004925","article-title":"Impairment of BRCA1-related DNA double-strand break repair leads to ovarian aging in mice and humans","volume":"5","author":"Titus","year":"2013","journal-title":"Sci. Transl. Med."},{"key":"10.1016\/j.mad.2020.111425_bib0390","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1111\/nyas.13533","article-title":"Revisiting the genomic hypomethylation hypothesis of aging","volume":"1418","author":"Unnikrishnan","year":"2018","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"10.1016\/j.mad.2020.111425_bib0395","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1016\/j.pharmthera.2018.11.001","article-title":"The role of DNA methylation in epigenetics of aging","volume":"195","author":"Unnikrishnan","year":"2019","journal-title":"Pharmacol. Ther."},{"key":"10.1016\/j.mad.2020.111425_bib0400","doi-asserted-by":"crossref","first-page":"12492","DOI":"10.1073\/pnas.1323955111","article-title":"Interleukin-1 deficiency prolongs ovarian lifespan in mice","volume":"111","author":"Uri-Belapolsky","year":"2014","journal-title":"Proc. Natl. Acad. Sci."},{"key":"10.1016\/j.mad.2020.111425_bib0405","article-title":"Parity-dependent hemosiderin and lipofuscin accumulation in the reproductively aged mouse ovary","volume":"2018","author":"Urzua","year":"2018","journal-title":"Anal. Cell. Pathol. Amst. (Amst)"},{"key":"10.1016\/j.mad.2020.111425_bib0410","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1007\/s00418-020-01890-w","article-title":"The loss of global DNA methylation due to decreased DNMT expression in the postnatal mouse ovaries may associate with infertility emerging during ovarian aging","volume":"154","author":"Uysal","year":"2020","journal-title":"Histochem. Cell Biol."},{"key":"10.1016\/j.mad.2020.111425_bib0415","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1111\/j.1474-9726.2009.00481.x","article-title":"DNA damage response and cellular senescence in tissues of aging mice","volume":"8","author":"Wang","year":"2009","journal-title":"Aging Cell"},{"key":"10.1016\/j.mad.2020.111425_bib0420","doi-asserted-by":"crossref","first-page":"e12651","DOI":"10.1111\/aji.12651","article-title":"Mitochondrial dysfunction and ovarian aging","volume":"77","author":"Wang","year":"2017","journal-title":"Am. J. Reprod. Immunol."},{"key":"10.1016\/j.mad.2020.111425_bib0425","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1016\/j.cell.2020.01.009","article-title":"Single-cell transcriptomic atlas of primate ovarian aging","volume":"180","author":"Wang","year":"2020","journal-title":"Cell"},{"key":"10.1016\/j.mad.2020.111425_bib0430","doi-asserted-by":"crossref","first-page":"1081","DOI":"10.1097\/gme.0b013e3182517bd0","article-title":"Early menopause predicts future coronary heart disease and stroke: the Multi-Ethnic Study of Atherosclerosis","volume":"19","author":"Wellons","year":"2012","journal-title":"Menopause"},{"key":"10.1016\/j.mad.2020.111425_bib0435","doi-asserted-by":"crossref","first-page":"2436","DOI":"10.1101\/gad.179184.111","article-title":"Mechanisms and functions of Tet protein-mediated 5-methylcytosine oxidation","volume":"25","author":"Wu","year":"2011","journal-title":"Genes Dev."},{"key":"10.1016\/j.mad.2020.111425_bib0440","doi-asserted-by":"crossref","first-page":"3590","DOI":"10.18632\/aging.101617","article-title":"The senescent cell epigenome","volume":"10","author":"Yang","year":"2018","journal-title":"Aging (Albany NY)"},{"key":"10.1016\/j.mad.2020.111425_bib0445","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.ebiom.2018.09.015","article-title":"Fisetin is a senotherapeutic that extends health and lifespan","volume":"36","author":"Yousefzadeh","year":"2018","journal-title":"EBioMedicine"},{"key":"10.1016\/j.mad.2020.111425_bib0450","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1016\/j.stemcr.2017.05.026","article-title":"Genome-wide, single-cell DNA methylomics reveals increased non-CpG methylation during human oocyte maturation","volume":"9","author":"Yu","year":"2017","journal-title":"Stem Cell Reports"},{"key":"10.1016\/j.mad.2020.111425_bib0455","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1007\/s10815-012-9780-4","article-title":"Abnormal DNA methylation in oocytes could be associated with a decrease in reproductive potential in old mice","volume":"29","author":"Yue","year":"2012","journal-title":"J. Assist. Reprod. Genet."},{"key":"10.1016\/j.mad.2020.111425_bib0460","doi-asserted-by":"crossref","first-page":"1069","DOI":"10.1007\/s10815-015-0483-5","article-title":"Increased DNA damage and repair deficiency in granulosa cells are associated with ovarian aging in rhesus monkey","volume":"32","author":"Zhang","year":"2015","journal-title":"J. Assist. Reprod. Genet."},{"key":"10.1016\/j.mad.2020.111425_bib0465","doi-asserted-by":"crossref","first-page":"644","DOI":"10.1111\/acel.12344","article-title":"The Achilles\u2019 heel of senescent cells: from transcriptome to senolytic drugs","volume":"14","author":"Zhu","year":"2015","journal-title":"Aging Cell"}],"container-title":["Mechanisms of Ageing and Development"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0047637420302219?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0047637420302219?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,9,23]],"date-time":"2025-09-23T17:43:14Z","timestamp":1758649394000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0047637420302219"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3]]},"references-count":93,"alternative-id":["S0047637420302219"],"URL":"https:\/\/doi.org\/10.1016\/j.mad.2020.111425","relation":{},"ISSN":["0047-6374"],"issn-type":[{"value":"0047-6374","type":"print"}],"subject":[],"published":{"date-parts":[[2021,3]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Cellular hallmarks of aging emerge in the ovary prior to primordial follicle depletion","name":"articletitle","label":"Article Title"},{"value":"Mechanisms of Ageing and Development","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.mad.2020.111425","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2020 Elsevier B.V. All rights reserved.","name":"copyright","label":"Copyright"}],"article-number":"111425"}}