Cellular hallmarks of aging emerge in the ovary prior to primordial follicle depletion
Open accessAbstract
Decline in ovarian reserve with advancing age is associated with reduced fertility and the emergence of metabolic disturbances, osteoporosis, and neurodegeneration. Recent studies have provided insight into connections between ovarian insufficiency and systemic aging, although the basic mechanisms that promote ovarian reserve depletion remain unknown. Here, we sought to determine if chronological age is linked to changes in ovarian cellular senescence, transcriptomic, and epigenetic mechanisms in a mouse model. Histological assessments and transcriptional analyses revealed the accumulation of lipofuscin aggresomes and senescence-related transcripts (Cdkn1a, Cdkn2a, Pai-1 and Hmgb1) significantly increased with advancing age. Transcriptomic profiling and pathway analyses following RNA sequencing, revealed an upregulation of genes related to pro-inflammatory stress and cell-cycle inhibition, whereas genes involved in cell-cycle progression were downregulated; which could be indicative of senescent cell accumulation. The emergence of these senescence-related markers preceded the dramatic decline in primordial follicle reserve observed. Whole Genome Oxidative Bisulfite Sequencing (WGoxBS) found no genome-wide or genomic context-specific DNA methylation and hydroxymethylation changes with advancing age. These findings suggest that cellular senescence may contribute to ovarian aging, and thus, declines in ovarian follicular reserve. Cell-type-specific analyses across the reproductive lifespan are needed to fully elucidate the mechanisms that promote ovarian insufficiency.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Secretion of SASP factors such as Ccl8, CCL5 and Crlf1 increases with age in mouse ovaries.
“The secretion of SASP factors such as Ccl8 (ref. 239), CCL5 (ref. 241) and the pro-inflammatory related gene Crlf1 (ref. 239) also increases with age.”
From SenNet recommendations for detecting senescent cells in different tissues (2024) · cites this paper as [239]
The Results (Transcriptomic analysis; page unavailable) report that Ccl8 and Crlf1 expression increased with age in mouse ovaries, with RT-qPCR confirming the RNA-seq findings. The paper measured gene expression, not secretion of those factors. CCL5 is attached to a different citation in the citing sentence and is not assessed here. (LLM, conf=0.86)
Experimental — accuracy not yet measuredIn ovaries from mice of advanced reproductive age, cells classified as senescent have increased Cdkn2a, Cdkn1a, Serpine1 and Hmgb1.
“In ovaries from mice of advanced reproductive age, cells classified as senescent are characterized by increased expression of Cdkn2a (refs. 238–240), Cdkn1a, Serpine1 and Hmgb1 (ref. 239).”
From SenNet recommendations for detecting senescent cells in different tissues (2024) · cites this paper as [239]
The Results (“Senescence markers”; page not provided) report increased ovarian Cdkn1a, Cdkn2a, PAI-1/Serpine1 and HMGB1 expression in older mice. The Methods describe qPCR of ovarian samples, not expression measured specifically in cells classified as senescent. That cell-specific part of the claim is unsupported. (LLM, conf=0.88)
Experimental — accuracy not yet measuredThese aged mouse ovary cells exhibit increased lysosomal content, indicated by lipofuscin aggregates and SA-β-gal staining in the stromal compartment.
“Additionally, these cells exhibit increased lysosomal content, as indicated by accumulation of lipofuscin aggregates (known as ‘aggresomes’)239 and by SA-β-gal staining in the stromal compartment241.”
From SenNet recommendations for detecting senescent cells in different tissues (2024) · cites this paper as [239]
Citation 241 is attached to the SA-β-gal staining in the stromal compartment, not to the lipofuscin finding cited as 239. The Discussion mentions β-galactosidase staining only as a comparator for lipofuscin staining; the passages found do not report SA-β-gal staining in ovarian stroma (searched for SA-β-gal, stromal compartment, and ovarian stroma). (LLM, conf=0.76)
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Analysis of Relative Gene Expression Data Using Real-Time Quantitative PCR and the 2−ΔΔCT Method
Livak, K. J., & Schmittgen, T. D. (2001) · Methods · doi:10.1006/meth.2001.1262 · Cited by 180,860 · see citing works
Differential expression analysis for sequence count data
Anders, S., & Huber, W. (2010) · Genome Biology · doi:10.1186/gb-2010-11-10-r106 · Cited by 15,581 · see citing works
López-Otín, C., Blasco, M. A., Partridge, L., Serrano, M., & Kroemer, G. (2013) · Cell · doi:10.1016/j.cell.2013.05.039 · Cited by 14,982 · see citing works
Conversion of 5-Methylcytosine to 5-Hydroxymethylcytosine in Mammalian DNA by MLL Partner TET1
Tahiliani, M., Koh, K. P., Shen, Y., Pastor, W. A., Bandukwala, H., Brudno, Y., Agarwal, S., Iyer, L. M., Liu, D. R., Aravind, L., et al. (2009) · Science · doi:10.1126/science.1170116 · Cited by 5,836 · see citing works
DNA methylation and its basic function
Moore, L. D., Le, T., & Fan, G. (2013) · Neuropsychopharmacology · doi:10.1038/npp.2012.112 · Cited by 4,906 · see citing works
Mutation of the mouse klotho gene leads to a syndrome resembling ageing
Kuro-o, M., Matsumura, Y., Aizawa, H., Kawaguchi, H., Suga, T., Utsugi, T., Ohyama, Y., Kurabayashi, M., Kaname, T., Kume, E., et al. (1997) · Nature · doi:10.1038/36285 · Cited by 3,837 · see citing works
Clearance of p16Ink4a-positive senescent cells delays ageing-associated disorders
Baker, D. J., Wijshake, T., Tchkonia, T., LeBrasseur, N. K., Childs, B. G., van de Sluis, B., Kirkland, J. L., & van Deursen, J. M. (2011) · Nature · doi:10.1038/nature10600 · Cited by 3,670 · see citing works
Cellular senescence: from physiology to pathology
Muñoz-Espín, D., & Serrano, M. (2014) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3823 · Cited by 2,818 · see citing works
The Nuclear DNA Base 5-Hydroxymethylcytosine Is Present in Purkinje Neurons and the Brain
Kriaucionis, S., & Heintz, N. (2009) · Science · doi:10.1126/science.1169786 · Cited by 2,700 · see citing works
Hallmarks of Cellular Senescence
Hernandez-Segura, A., Nehme, J., & Demaria, M. (2018) · Trends in Cell Biology · doi:10.1016/j.tcb.2018.02.001 · Cited by 2,605 · see citing works
The Achilles' heel of senescent cells: from transcriptome to senolytic drugs
Zhu, Y., Tchkonia, T., Pirtskhalava, T., Gower, A. C., Ding, H., Giorgadze, N., Palmer, A. K., Ikeno, Y., Hubbard, G. B., Lenburg, M., et al. (2015) · Aging Cell · doi:10.1111/acel.12344 · Cited by 2,562 · see citing works
Self-citationThe Role of DNA Methylation in Mammalian Epigenetics
Jones, P. A., & Takai, D. (2001) · Science · doi:10.1126/science.1063852 · Cited by 2,063 · see citing works
Four faces of cellular senescence
Rodier, F., & Campisi, J. (2011) · Journal of Cell Biology · doi:10.1083/jcb.201009094 · Cited by 2,016 · see citing works
Cellular senescence and the senescent secretory phenotype: therapeutic opportunities
Tchkonia, T., Zhu, Y., van Deursen, J., Campisi, J., & Kirkland, J. L. (2013) · Journal of Clinical Investigation · doi:10.1172/jci64098 · Cited by 1,774 · see citing works
Ink4a/Arf expression is a biomarker of aging
Krishnamurthy, J., Torrice, C., Ramsey, M. R., Kovalev, G. I., Al-Regaiey, K., Su, L., & Sharpless, N. E. (2004) · Journal of Clinical Investigation · doi:10.1172/jci22475 · Cited by 1,486 · see citing works
The DNA methyltransferase family: a versatile toolkit for epigenetic regulation
Lyko, F. (2017) · Nature Reviews Genetics · doi:10.1038/nrg.2017.80 · Cited by 1,475 · see citing works
Accelerated disappearance of ovarian follicles in mid-life: implications for forecasting menopause
Faddy, M. J., Gosden, R. G., Gougeon, A., Richardson, S. J., & Nelson, J. F. (1992) · Human Reproduction · doi:10.1093/oxfordjournals.humrep.a137570 · Cited by 1,361 · see citing works
Ovarian aging: mechanisms and clinical consequences
Broekmans, F. J., Soules, M. R., & Fauser, B. C. (2009) · Endocrine Reviews · doi:10.1210/er.2009-0006 · Cited by 1,248 · see citing works
Detecting DNA cytosine methylation using nanopore sequencing
Simpson, J. T., Workman, R. E., Zuzarte, P. C., David, M., Dursi, L. J., & Timp, W. (2017) · Nature Methods · doi:10.1038/nmeth.4184 · Cited by 1,109 · see citing works
Forging a signature of in vivo senescence
Sharpless, N. E., & Sherr, C. J. (2015) · Nature Reviews Cancer · doi:10.1038/nrc3960 · Cited by 1,104 · see citing works
Repetitive Elements May Comprise Over Two-Thirds of the Human Genome
de Koning, A. P. J., Gu, W., Castoe, T. A., Batzer, M. A., & Pollock, D. D. (2011) · PLoS Genetics · doi:10.1371/journal.pgen.1002384 · Cited by 1,099 · see citing works
A quantitative and cytological study of germ cells in human ovaries
Baker, T. G. (1963) · Proceedings of the Royal Society B Biological Sciences · doi:10.1098/rspb.1963.0055 · Cited by 1,094 · see citing works
Role of TET enzymes in DNA methylation, development, and cancer
Rasmussen, K. D., & Helin, K. (2016) · Genes & Development · doi:10.1101/gad.276568.115 · Cited by 1,040 · see citing works
Fisetin is a senotherapeutic that extends health and lifespan
Yousefzadeh, M. J., Zhu, Y., McGowan, S. J., Angelini, L., Fuhrmann-Stroissnigg, H., Xu, M., Ling, Y. Y., Melos, K. I., Pirtskhalava, T., Inman, C. L., et al. (2018) · EBioMedicine · doi:10.1016/j.ebiom.2018.09.015 · Cited by 1,032 · see citing works
Unmasking Transcriptional Heterogeneity in Senescent Cells
Hernandez-Segura, A., de Jong, T. V., Melov, S., Guryev, V., Campisi, J., & Demaria, M. (2017) · Current Biology · doi:10.1016/j.cub.2017.07.033 · Cited by 972 · see citing works
Quantitative Sequencing of 5-Methylcytosine and 5-Hydroxymethylcytosine at Single-Base Resolution
Booth, M. J., Branco, M. R., Ficz, G., Oxley, D., Krueger, F., Reik, W., & Balasubramanian, S. (2012) · Science · doi:10.1126/science.1220671 · Cited by 923 · see citing works
Kurz, D. J., Decary, S., Hong, Y., & Erusalimsky, J. D. (2000) · Journal of Cell Science · doi:10.1242/jcs.113.20.3613 · Cited by 899 · see citing works
The Mammalian Ovary from Genesis to Revelation
Edson, M. A., Nagaraja, A. K., & Matzuk, M. M. (2009) · Endocrine Reviews · doi:10.1210/er.2009-0012 · Cited by 828 · see citing works
Lanaspa, M. A., Ishimoto, T., Li, N., Cicerchi, C., Orlicky, D. J., Ruzycki, P. A., Rivard, C. J., Inaba, S., Roncal-Jiménez, C. A., Bales, E. S., et al. (2013) · Nature Communications · doi:10.1038/ncomms3929 · Cited by 796 · see citing works
Methods for quantifying follicular numbers within the mouse ovary
Myers, M. A., Britt, K. L., Wreford, N. G., Ebling, F. J. P., & KERR, J. B. (2004) · Reproduction · doi:10.1530/rep.1.00095 · Cited by 762 · see citing works
Dynamic CpG island methylation landscape in oocytes and preimplantation embryos
Smallwood, S. A., Tomizawa, S.-I., Krueger, F., Ruf, N., Carli, N., Segonds-Pichon, A., Sato, S., Hata, K., Andrews, S., & Kelsey, G. (2011) · Nature Genetics · doi:10.1038/ng.864 · Cited by 701 · see citing works
DNA damage response and cellular senescence in tissues of aging mice
Wang, C., Jurk, D., Maddick, M., Nelson, G., Martin‐Ruiz, C., & Von Zglinicki, T. (2009) · Aging Cell · doi:10.1111/j.1474-9726.2009.00481.x · Cited by 696 · see citing works
Mechanisms and functions of Tet protein-mediated 5-methylcytosine oxidationPreprint
Wu, H., & Zhang, Y. (2011) · Genes & Development · doi:10.17615/800j-yk16 · Cited by 665 · see citing works
Kortlever, R. M., Higgins, P. J., & Bernards, R. (2006) · Nature Cell Biology · doi:10.1038/ncb1448 · Cited by 637 · see citing works
The origin of interspersed repeats in the human genome
Smit, A. F. A. (1996) · Current Opinion in Genetics & Development · doi:10.1016/s0959-437x(96)80030-x · Cited by 611 · see citing works
Calos, M. P., & Miller, J. H. (1980) · Cell · doi:10.1016/0092-8674(80)90305-0 · Cited by 595 · see citing works
Single-Cell Transcriptomic Atlas of Primate Ovarian Aging
Wang, S., Zheng, Y., Li, J., Yu, Y., Zhang, W., Song, M., Liu, Z., Min, Z., Hu, H., Jing, Y., et al. (2020) · Cell · doi:10.1016/j.cell.2020.01.009 · Cited by 592 · see citing works
Impairment of BRCA1-Related DNA Double-Strand Break Repair Leads to Ovarian Aging in Mice and Humans
Titus, S., Li, F., Stobezki, R., Akula, K., Ünsal, E., Jeong, K., Dickler, M. N., Robson, M. E., MOY, F. H., Goswami, S., et al. (2013) · Science Translational Medicine · doi:10.1126/scitranslmed.3004925 · Cited by 523 · see citing works
Booth, L. N., & Brunet, A. (2016) · Molecular Cell · doi:10.1016/j.molcel.2016.05.013 · Cited by 499 · see citing works
Mehlmann, L. M. (2005) · Reproduction · doi:10.1530/rep.1.00793 · Cited by 484 · see citing works
Age at Menopause, Cause-Specific Mortality and Total Life Expectancy
Ossewaarde, M. E., Bots, M. L., Verbeek, A. L. M., Peeters, P. H. M., van der Graaf, Y., Grobbee, D. E., & van der Schouw, Y. T. (2005) · Epidemiology · doi:10.1097/01.ede.0000165392.35273.d4 · Cited by 443 · see citing works
Lipofuscin: Formation, Distribution, and Metabolic Consequences
JUNG, T., BADER, N., & GRUNE, T. (2007) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1404.008 · Cited by 415 · see citing works
Georgakopoulou, E., Tsimaratou, K., Evangelou, K., Fernandez, M.-P., Zoumpourlis, V, Trougakos, I., Kletsas, D., Bartek, J., Serrano, M., & Gorgoulis, V. (2012) · Aging · doi:10.18632/aging.100527 · Cited by 390 · see citing works
Serum Anti-Müllerian Hormone Levels Reflect the Size of the Primordial Follicle Pool in Mice
Kevenaar, M. E., Meerasahib, M. F., Kramer, P., van de Lang-Born, B. M. N., de Jong, F. H., Groome, N. P., Themmen, A. P. N., & Visser, J. A. (2006) · Endocrinology · doi:10.1210/en.2005-1588 · Cited by 389 · see citing works
Genes that escape from X inactivation
Berletch, J. B., Yang, F., Xu, J., Carrel, L., & Disteche, C. M. (2011) · Human Genetics · doi:10.1007/s00439-011-1011-z · Cited by 384 · see citing works
The role of DNA methylation in epigenetics of aging
Unnikrishnan, A., Freeman, W. M., Jackson, J. A., Wren, J. D., Porter, H. L., & Richardson, A. G. (2018) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2018.11.001 · Cited by 381 · see citing works
Self-citationReproductive age-associated fibrosis in the stroma of the mammalian ovary
Briley, S. M., Jasti, S., McCracken, J. M., Hornick, J. E., Fegley, B., Pritchard, M. T., & Duncan, F. E. (2016) · Reproduction · doi:10.1530/rep-16-0129 · Cited by 373 · see citing works
Early menopause predicts future coronary heart disease and stroke
Wellons, M., Ouyang, P., Schreiner, P. J., Herrington, D. M., & Vaidya, D. M. (2012) · Menopause The Journal of The North American Menopause Society · doi:10.1097/gme.0b013e3182517bd0 · Cited by 320 · see citing works
Non-CG Methylation in the Human Genome
He, Y., & Ecker, J. R. (2015) · Annual Review of Genomics and Human Genetics · doi:10.1146/annurev-genom-090413-025437 · Cited by 263 · see citing works
Malaquin, N., Martinez, A., & Rodier, F. (2016) · Experimental Gerontology · doi:10.1016/j.exger.2016.05.010 · Cited by 247 · see citing works
Oxidative stress and alterations in DNA methylation: two sides of the same coin in reproduction
Menezo, Y. J. R., Silvestris, E., Dale, B., & Elder, K. T. (2016) · Reproductive BioMedicine Online · doi:10.1016/j.rbmo.2016.09.006 · Cited by 247 · see citing works
Meiotic Origins of Maternal Age-Related Aneuploidy1
Chiang, T., Schultz, R. M., & Lampson, M. A. (2011) · Biology of Reproduction · doi:10.1095/biolreprod.111.094367 · Cited by 219 · see citing works
Developmental and endocrine aspects of normal ovarian aging
Velde, E. R. T., Scheffer, G. J., Dorland, M., Broekmans, F. J., & Fauser, B. C. J. M. (1998) · Molecular and Cellular Endocrinology · doi:10.1016/s0303-7207(98)00171-3 · Cited by 210 · see citing works
The current knowledge on radiosensitivity of ovarian follicle development stages
Adriaens, I., Smitz, J. E. J., & Jacquet, P. (2009) · Human Reproduction Update · doi:10.1093/humupd/dmn063 · Cited by 204 · see citing works
Selesniemi, K. L., Lee, H., & Tilly, J. L. (2008) · Aging Cell · doi:10.1111/j.1474-9726.2008.00409.x · Cited by 158 · see citing works
Overweight, Obesity, Diabetes, and Risk of Breast Cancer: Interlocking Pieces of the Puzzle
Vecchia, C. L., Giordano, S. H., Hortobágyi, G. N., & Chabner, B. A. (2011) · The Oncologist · doi:10.1634/theoncologist.2011-0050 · Cited by 156 · see citing works
Interleukin-1 deficiency prolongs ovarian lifespan in mice
Uri-Belapolsky, S., Shaish, A., Eliyahu, E., Grossman, H., Levi, M., Chuderland, D., Ninio-Many, L., Hasky, N., Shashar, D., Almog, T., et al. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1323955111 · Cited by 136 · see citing works
Stout, M. B., Tchkonia, T., Pirtskhalava, T., Palmer, A. K., List, E. O., Berryman, D. E., Lubbers, E. R., Escande, C., Spong, A., Masternak, M. M., et al. (2014) · Aging · doi:10.18632/aging.100681 · Cited by 135 · see citing works
Self-citationEffect of aging on 5-hydroxymethylcytosine in the mouse hippocampus
Chen, H., Dzitoyeva, S., & Manev, H. (2012) · Restorative Neurology and Neuroscience · doi:10.3233/rnn-2012-110223 · Cited by 129 · see citing works
The role and mechanisms of DNA methylation in the oocyte
Sendžikaitė, G., & Kelsey, G. (2019) · Essays in Biochemistry · doi:10.1042/ebc20190043 · Cited by 129 · see citing works
Evangelou, K., & Gorgoulis, V. G. (2017) · Methods in Molecular Biology · doi:10.1007/978-1-4939-6670-7_10 · Cited by 124 · see citing works
Constitutively active Foxo3 in oocytes preserves ovarian reserve in mice
Pelosi, E., Omari, S., Michel, M., Ding, J., Amano, T., Forabosco, A., Schlessinger, D., & Ottolenghi, C. (2013) · Nature Communications · doi:10.1038/ncomms2861 · Cited by 122 · see citing works
Revisiting the genomic hypomethylation hypothesis of aging
Unnikrishnan, A., Hadad, N., Masser, D. R., Jackson, J., Freeman, W. M., & Richardson, A. (2018) · Annals of the New York Academy of Sciences · doi:10.1111/nyas.13533 · Cited by 113 · see citing works
Self-citationTransplantation of Young Ovaries to Old Mice Increased Life Span in Transplant Recipients
Mason, J. B., Cargill, S. L., Anderson, G. B., & Carey, J. R. (2009) · The Journals of Gerontology Series A · doi:10.1093/gerona/glp134 · Cited by 112 · see citing works
Mitochondrial dysfunction and ovarian aging
Wang, T., Zhang, M., Jiang, Z., & Seli, E. U. (2017) · American Journal of Reproductive Immunology · doi:10.1111/aji.12651 · Cited by 108 · see citing works
Infertility service use among U.S. women: 1995 and 2002
Chandra, A., & Stephen, E. H. (2008) · Fertility and Sterility · doi:10.1016/j.fertnstert.2008.10.049 · Cited by 102 · see citing works
Yue, M., Fu, X., Zhou, G., Hou, Y., Du, M., Wang, L., & Zhu, S. (2012) · Journal of Assisted Reproduction and Genetics · doi:10.1007/s10815-012-9780-4 · Cited by 98 · see citing works
Yu, B., Dong, X., Gravina, S., Kartal, Ö., Schimmel, T., Cohen, J., Tortoriello, D. V., Zody, R., Hawkins, R. D., & Vijg, J. (2017) · Stem Cell Reports · doi:10.1016/j.stemcr.2017.05.026 · Cited by 96 · see citing works
Transcription and chromatin determinants of de novo DNA methylation timing in oocytes
Gahurová, L., Tomizawa, S.-I., Smallwood, S. A., Stewart-Morgan, K. R., Saadeh, H., Kim, J., Andrews, S., Chen, T., & Kelsey, G. (2017) · Epigenetics & Chromatin · doi:10.1186/s13072-017-0133-5 · Cited by 93 · see citing works
Zhang, D., Zhang, X., Zeng, M., Yuan, J., Liu, M., Yin, Y., Wu, X., Keefe, D. L., & Liu, L. (2015) · Journal of Assisted Reproduction and Genetics · doi:10.1007/s10815-015-0483-5 · Cited by 88 · see citing works
Senescence, Wound Healing, and Cancer: the PAI-1 Connection
Kortlever, R. M., & Bernards, R. (2006) · Cell Cycle · doi:10.4161/cc.5.23.3510 · Cited by 84 · see citing works
Induction of congenital anomalies in offspring of female mice exposed to varying doses of X-rays
Kirk, M., & Lyon, M. F. (1982) · Mutation research. Fundamental and molecular mechanisms of mutagenesis · doi:10.1016/0027-5107(82)90191-9 · Cited by 84 · see citing works
Prothero, K. E., Stahl, J. M., & Carrel, L. (2009) · Chromosome Research · doi:10.1007/s10577-009-9063-9 · Cited by 78 · see citing works
Prevention of age-related changes in hippocampal levels of 5-methylcytidine by caloric restriction
Chouliaras, L., van den Hove, D. L. A., Kenis, G., Keitel, S., Hof, P. R., van Os, J., Steinbusch, H. W. M., Schmitz, C., & Rutten, B. P. F. (2012) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2011.06.003 · Cited by 78 · see citing works
Yang, N., & Sen, P. (2018) · Aging · doi:10.18632/aging.101617 · Cited by 74 · see citing works
Sharov, A. A., Falco, G., Piao, Y., Poosala, S., Becker, K. G., Zonderman, A. B., Longo, D. L., Schlessinger, D., & Ko, M. S. H. (2008) · BMC Biology · doi:10.1186/1741-7007-6-24 · Cited by 66 · see citing works
Influence of menopause on high density lipoprotein-cholesterol and lipids
Kim, C. J., Kim, T. H., Ryu, W. S., & Ryoo, U. H. (2000) · Journal of Korean Medical Science · doi:10.3346/jkms.2000.15.4.380 · Cited by 65 · see citing works
Turning over DNA methylation in the mind
Lister, R., & Mukamel, E. A. (2015) · Frontiers in Neuroscience · doi:10.3389/fnins.2015.00252 · Cited by 60 · see citing works
Early Life Stress Delays Sexual Maturation in Female Mice
Manzano-Nieves, G., Nitenson, A. S., Lee, H.-I., Gallo, M. E., Aguilar, Z., Johnsen, A., Bravo, M., & Bath, K. G. (2019) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2019.00027 · Cited by 50 · see citing works
Masser, D. R., Bixler, G. V., Brucklacher, R. M., Yan, H., Giles, C. B., Wren, J. D., Sonntag, W. E., & Freeman, W. M. (2014) · The Journals of Gerontology Series A · doi:10.1093/gerona/glu091 · Cited by 48 · see citing works
Self-citationHadad, N., Masser, D. R., Logan, S., Wronowski, B., Mangold, C. A., Clark, N. W., Otalora, L., Unnikrishnan, A., Ford, M. M., Giles, C. B., et al. (2016) · Epigenetics & Chromatin · doi:10.1186/s13072-016-0080-6 · Cited by 48 · see citing works
Self-citationDynamic changes of DNA epigenetic marks in mouse oocytes during natural and accelerated aging
Qian, Y., Tu, J., Tang, N. L. S., Kong, G. W. S., Chung, J. P. W., Chan, W., & Lee, T. (2015) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2015.05.005 · Cited by 45 · see citing works
Transcription factors in the maintenance and survival of primordial follicles
Lim, E., & Choi, Y. (2012) · Daehan saengsik uihak hoeji/Clinical and experimental reproductive medicine · doi:10.5653/cerm.2012.39.4.127 · Cited by 44 · see citing works
Chucair‐Elliott, A. J., Ocañas, S. R., Stanford, D. R., Ansere, V. A., Buettner, K. B., Porter, H. L., Eliason, N. L., Reid, J. J., Sharpe, A. L., Stout, M. B., et al. (2020) · Communications Biology · doi:10.1038/s42003-020-01418-x · Cited by 37 · see citing works
Self-citationUysal, F., & Ozturk, S. (2020) · Histochemistry and Cell Biology · doi:10.1007/s00418-020-01890-w · Cited by 35 · see citing works
Huang, Y., Zhao, Y., Yu, Y., Li, R., Lin, S., Zhang, C., Liu, P., & Qiao, J. (2015) · Reproductive BioMedicine Online · doi:10.1016/j.rbmo.2015.03.001 · Cited by 30 · see citing works
Ovarian transcriptome associated with reproductive senescence in the long-living Ames dwarf mice
Schneider, A., Matkovich, S. J., Saccon, T. D., Victoria, B., Spinel, L., Lavasani, M., Bartke, A., Golusiński, P., & Masternak, M. M. (2016) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2016.09.019 · Cited by 29 · see citing works
Self-citationParity-Dependent Hemosiderin and Lipofuscin Accumulation in the Reproductively Aged Mouse Ovary
Urzúa, U., Chacón, C., Espinoza, R., Martínez, S., & Hernandez, N. (2018) · Analytical Cellular Pathology · doi:10.1155/2018/1289103 · Cited by 29 · see citing works
Ryu, S. H., Kang, K., Yoo, T., Joe, C., & Chung, J. (2011) · Experimental Gerontology · doi:10.1016/j.exger.2011.07.001 · Cited by 28 · see citing works
Chucair‐Elliott, A. J., Ocañas, S. R., Stanford, D. R., Hadad, N., Wronowski, B., Otalora, L., Stout, M. B., & Freeman, W. M. (2019) · GeroScience · doi:10.1007/s11357-019-00090-2 · Cited by 23 · see citing works
Self-citationSaccon, T. D., Rovani, M. T., Garcia, D. N., Mondadori, R. G., Cruz, L. A. X., Barros, C. C., Bartke, A., Masternak, M. M., & Schneider, A. (2020) · Experimental Gerontology · doi:10.1016/j.exger.2020.110851 · Cited by 19 · see citing works
Self-citationThe endocrinology of ovarian steroid secretion
Baird, D. T. (1974) · European Journal of Obstetrics & Gynecology and Reproductive Biology · doi:10.1016/0028-2243(74)90006-9 · Cited by 18 · see citing works
Flagged first, then by citations
1 of the 93 references couldn’t be matched to a known paper.
Research works printed but not linked: 3
- Snyder AN, Crane JS, 2020. Histology, Lipofuscin, StatPearls, Treasure Island (FL). 30726043
- te Velde ER, Scheffer GJ, Dorland M, Broekmans FJ, Fauser BCJM, 1998b. Developmental and endocrine aspects of normal ovarian aging. Molecular and Cellular Endocrinology 145, 67– 73. 9922101
- Urzua U, Chacon C, Espinoza R, Martínez S, Hernandez N, 2018b. Parity-Dependent Hemosiderin and Lipofuscin Accumulation in the Reproductively Aged Mouse Ovary. Analytical Cellular Pathology 2018. PMC5874974 29736365
Cited by
Sorted by citations
SenNet recommendations for detecting senescent cells in different tissues
Suryadevara, V., Hudgins, A. D., Rajesh, A., Pappalardo, A., Karpova, A., Dey, A. K., Hertzel, A., Agudelo, A., Rocha, A., Soygur, B., et al. (2024) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-024-00738-8 · Cited by 408 · see citing works
“Additionally, these cells exhibit increased lysosomal content, as indicated by accumulation of lipofuscin aggregates (known as ‘aggresomes’) 239 and by SA-β-gal staining in the stromal compartment 241 Apart from physiological ageing, treatments that accelerate reproductive ageing through genotoxic…”
The role of oxidative stress in ovarian aging: a review
Yan, F., Zhao, Q., Li, Y., Zheng, Z., Kong, X., Shu, C., Liu, Y., & Shi, Y. (2022) · Journal of Ovarian Research · doi:10.1186/s13048-022-01032-x · Cited by 307 · see citing works
A single-cell atlas of the aging mouse ovary
Isola, J. V. V., Ocañas, S. R., Hubbart, C. R., Ko, S.-H., Mondal, S. A., Hense, J. D., Carter, H. N. C., Schneider, A., Kovats, S., Alberola‐Ila, J., et al. (2024) · Nature Aging · doi:10.1038/s43587-023-00552-5 · Cited by 200 · see citing works
Self-citationSpatiotemporal transcriptomic changes of human ovarian aging and the regulatory role of FOXP1
Wu, M., Tang, W., Chen, Y., Xue, L., Dai, J. Y., Li, Y., Zhu, X., Wu, C., Xiong, J., Zhang, J., et al. (2024) · Nature Aging · doi:10.1038/s43587-024-00607-1 · Cited by 151 · see citing works
Reproductive Ageing: Inflammation, immune cells, and cellular senescence in the aging ovary
Isola, J. V. V., Hense, J. D., Osorio, C. A. P., Biswas, S., Alberola‐Ila, J., Ocañas, S. R., Schneider, A., & Stout, M. B. (2024) · Reproduction · doi:10.1530/rep-23-0499 · Cited by 112 · see citing works
Self-citationOvarian aging in humans: potential strategies for extending reproductive lifespan
Cavalcante, M. B., Sampaio, O. G. M., Câmara, F. E. A., Schneider, A., Ávila, B. M., Prosczek, J. B., Masternak, M. M., & Campos, A. R. (2023) · GeroScience · doi:10.1007/s11357-023-00768-8 · Cited by 96 · see citing works
Self-citationWu, C., Chen, D., Stout, M. B., Wu, M., & Wang, S. (2025) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2025.01.005 · Cited by 74 · see citing works
Self-citationThe stromal microenvironment and ovarian aging: mechanisms and therapeutic opportunities
Shen, L., Liu, J., Luo, A., & Wang, S. (2023) · Journal of Ovarian Research · doi:10.1186/s13048-023-01300-4 · Cited by 74 · see citing works
Aging-Related Ovarian Failure and Infertility: Melatonin to the Rescue
Reiter, R., Sharma, R., Romero, A., Manucha, W., Tan, D., Zuccari, D. A. P. D. C., & Chuffa, L. G. D. A. (2023) · Antioxidants · doi:10.3390/antiox12030695 · Cited by 64 · see citing works
The role of cellular senescence in ovarian aging
Hense, J. D., Isola, J. V. V., Garcia, D. N., Magalhães, L. S., Masternak, M. M., Stout, M. B., & Schneider, A. (2024) · npj Aging · doi:10.1038/s41514-024-00157-1 · Cited by 59 · see citing works
Self-citationAli, I., Padhiar, A. A., Wang, T., He, L., Chen, M., Wu, S., Zhou, Y., & Zhou, G. (2022) · Cells · doi:10.3390/cells11233713 · Cited by 52 · see citing works
Comparative analysis of human and mouse ovaries across age
Gaylord, E. A., Foecke, M. H., Samuel, R. M., Soygur, B., Detweiler, A. M., McIntyre, T. I., Dorman, L. C., Borja, M., Laird, A. E., Arjyal, R., et al. (2025) · Science · doi:10.1126/science.adx0659 · Cited by 42 · see citing works
Isola, J. V. V., Zanini, B. M., Hense, J. D., Rincón, J. A. A., Garcia, D. N., Pereira, G. C., Vieira, A. D., Oliveira, T. L., Collares, T. V., Gasperin, B. G., et al. (2022) · Experimental Gerontology · doi:10.1016/j.exger.2021.111669 · Cited by 38 · see citing works
Self-citationMultiomics insights into the female reproductive aging
Wei, S., Tang, W., Chen, D., Xiong, J., Xue, L., Dai, Y., Guo, Y., Wu, C., Dai, J., Wu, M., et al. (2024) · Ageing Research Reviews · doi:10.1016/j.arr.2024.102245 · Cited by 37 · see citing works
Arslan, N. P., Taşkın, M., & Keleş, O. N. (2024) · Pharmaceutical Research · doi:10.1007/s11095-024-03704-3 · Cited by 36 · see citing works
Converse, A., Perry, M. J., Dipali, S. S., Isola, J. V. V., Kelly, E. B., Varberg, J. M., Zelinski, M. B., Gerton, J. L., Stout, M. B., Pritchard, M. T., et al. (2025) · PLoS Biology · doi:10.1371/journal.pbio.3003204 · Cited by 37 · see citing works
Self-citationSenolytic treatment reverses obesity-mediated senescent cell accumulation in the ovary
Hense, J. D., Garcia, D. N., Isola, J. V. V., Rincón, J. A. A., Zanini, B. M., Prosczek, J. B., Stout, M. B., Mason, J. B., Walsh, P. T., Brieño‐Enríquez, M. A., et al. (2022) · GeroScience · doi:10.1007/s11357-022-00573-9 · Cited by 36 · see citing works
Self-citationPQQ Dietary Supplementation Prevents Alkylating Agent-Induced Ovarian Dysfunction in Mice
Dai, X., Yi, X., Wang, Y., Xia, W., Tao, J., Wu, J., Miao, D., & Chen, L. (2022) · Frontiers in Endocrinology · doi:10.3389/fendo.2022.781404 · Cited by 35 · see citing works
Zaniker, E. J., Zhang, M., Hughes, L. M., LaFollette, L., Atazhanova, T., Trofimchuk, A., Babayev, E., & Duncan, F. E. (2024) · Biology of Reproduction · doi:10.1093/biolre/ioae050 · Cited by 34 · see citing works
Liu, C., Li, L., Yang, B., Zhao, Y., Dong, X., Zhu, L., Ren, X., Huang, B., Yue, J., Jin, L., et al. (2022) · BMC Genomics · doi:10.1186/s12864-022-08462-3 · Cited by 33 · see citing works
Ocañas, S. R., Ansere, V. A., Tooley, K. B., Hadad, N., Chucair‐Elliott, A. J., Stanford, D. R., Rice, S., Wronowski, B., Pham, K. D., Hoffman, J. M., et al. (2022) · Molecular Neurobiology · doi:10.1007/s12035-022-02860-0 · Cited by 25 · see citing works
Self-citationMaged, A. M., Mohsen, R. A., Salah, N., & Ragab, W. S. (2024) · BMC Pregnancy and Childbirth · doi:10.1186/s12884-024-06251-2 · Cited by 23 · see citing works
Cellular senescence in the pathogenesis of ovarian dysfunction
Harada, M. (2024) · Journal of obstetrics and gynaecology research · doi:10.1111/jog.15918 · Cited by 23 · see citing works
Influence of ovarian stromal cells on human ovarian follicle growth in a 3D environment
Grubliauskaité, M., Vlieghe, H., Moghassemi, S., Dadashzadeh, A., Camboni, A., Gudlevičienė, Ž., & Amorim, C. A. (2023) · Human Reproduction Open · doi:10.1093/hropen/hoad052 · Cited by 20 · see citing works
Emerging therapeutic strategies to mitigate female and male reproductive aging
Winstanley, Y. E., Stables, J., Gonzalez, M. B., Umehara, T., Norman, R. J., & Robker, R. L. (2024) · Nature Aging · doi:10.1038/s43587-024-00771-4 · Cited by 20 · see citing works
Senolytic treatment fails to improve ovarian reserve or fertility in female mice
Garcia, D. N., Hense, J. D., Zanini, B. M., Isola, J. V. V., Prosczek, J. B., Ashiqueali, S., Oliveira, T. L., Mason, J. B., Schadock, I., Barros, C. C., et al. (2024) · GeroScience · doi:10.1007/s11357-024-01089-0 · Cited by 18 · see citing works
Self-citationAlgal and Fungal Antioxidants Alleviate Oxidative Stress‐Induced Reproductive Defects
Arslan, N. P., Albayrak, S., Savaş, A., Hacımüftüoğlu, A., Orak, T., Ozdemir, A., Karadagoglu, O., Yildirim, S., Yılmaz, H. Ç., & Taşkın, M. (2025) · Food Science & Nutrition · doi:10.1002/fsn3.70301 · Cited by 17 · see citing works
Du, Y., Liu, J., Liu, S., Hu, J., Wang, S., Cui, K., Yan, K., Liu, X., Wu, N.-R., Yang, X., et al. (2021) · Food & Function · doi:10.1039/d1fo03194e · Cited by 15 · see citing works
Devrukhkar, P. R., Watson, M. A., Soygur, B., Wu, F., Bons, J., Anvari, H., Atazhanova, T., Martin, N., Tran, T., Schneider, K., et al. (2025) · Aging Cell · doi:10.1111/acel.70111 · Cited by 15 · see citing works
Dasatinib and quercetin increase testosterone and sperm concentration in mice
Garcia, D. N., Hense, J. D., Zanini, B. M., Isola, J. V. V., Pradieé, J., Prosczek, J. B., Rincón, J. A. A., Mondadori, R. G., Mason, J. B., Brieño‐Enríquez, M. A., et al. (2023) · Physiology International · doi:10.1556/2060.2023.00192 · Cited by 14 · see citing works
Self-citationA Molecular Perspective and Role of NAD+ in Ovarian Aging
Ahmed, M., Riaz, U., Lv, H., & Yang, L. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25094680 · Cited by 14 · see citing works
Isola, J. V. V., Biswas, S., Jayarathne, H. S. M., Hubbart, C. R., Hense, J. D., Matsuzaki, S., Kinter, M. T., Humphries, K. M., Ocañas, S. R., Sadagurski, M., et al. (2024) · GeroScience · doi:10.1007/s11357-024-01465-w · Cited by 13 · see citing works
Self-citationMASLD does not affect fertility and senolytics fail to prevent MASLD progression in male mice
Hense, J. D., Garcia, D. N., Zanini, B. M., Barreto, M. M., Pereira, G. C., Isola, J. V. V., de Brito, C., Fornalik, M., Mondal, S. A., Ávila, B. M., et al. (2024) · Scientific Reports · doi:10.1038/s41598-024-67697-0 · Cited by 12 · see citing works
Self-citationSpatial Transcriptomic Characteristics of the Aging Human Ovary
Zhang, M., Guo, F., Zhang, Q., Hu, Q., Sun, D., Ma, Y., Li, Y., Guo, M., Ding, H., Guo, Y., et al. (2025) · Aging Cell · doi:10.1111/acel.70288 · Cited by 11 · see citing works
Liu, Y., Mei, Q., Yang, J.-H., Shen, Q., Zou, M., Li, J., Li, H., Zhang, L., & Xiang, W. (2022) · Reproductive Biology and Endocrinology · doi:10.1186/s12958-022-01037-7 · Cited by 10 · see citing works
Effects of calorie, protein, and branched chain amino acid restriction on ovarian aging in mice
Veiga, G. B., Zanini, B. M., Garcia, D. N., Hense, J. D., Barreto, M. M., Isola, J. V. V., Mondadori, R. G., Masternak, M. M., Stout, M. B., & Schneider, A. (2024) · Reproductive Biology · doi:10.1016/j.repbio.2024.100856 · Cited by 10 · see citing works
Self-citationRevealing toxic secrets: How PAHs accelerate cellular ageing and trigger human diseases
Wang, Y., Xu, P., Chen, H., Guo, X., Gao, J., Wang, T., Yao, D., Li, X., Liu, B., & Yuan, J. (2025) · Toxicology · doi:10.1016/j.tox.2025.154219 · Cited by 10 · see citing works
Díaz-Hernández, V., Montaño, L. M., Caldelas, I., & Marmolejo-Valencia, A. (2022) · Biomedicines · doi:10.3390/biomedicines10123068 · Cited by 10 · see citing works
King, T. L., Underwood, K. B., Hansen, K. K., Kinter, M. T., Schneider, A., Masternak, M. M., & Mason, J. B. (2023) · GeroScience · doi:10.1007/s11357-023-00865-8 · Cited by 9 · see citing works
Self-citationThe Contribution of the Sheep and the Goat Model to the Study of Ovarian Ageing
Montenegro, L., Magalhães, P., Guerreiro, A. C., Brandão, C., Pinto, A., Almeida, H., Martins‐Bessa, A., & Silva, E. (2023) · Biology · doi:10.3390/biology12020270 · Cited by 8 · see citing works
Jiao, K.-Z., Li, Y., Huang, Y., Ndandala, C. B., Shi, G., Deng, S., Shi, H., Chen, H., Li, G., & Jiang, D. (2024) · Aquaculture · doi:10.1016/j.aquaculture.2024.740974 · Cited by 8 · see citing works
Fan, H., Li, C., Lv, Y., Qi, T., Huang, Y., Ma, L., Lan, Y., Chen, P., Lou, Z., & Zhou, J. (2025) · Ecotoxicology and Environmental Safety · doi:10.1016/j.ecoenv.2025.117940 · Cited by 8 · see citing works
A single-cell atlas of the aging murine ovaryPreprint
Isola, J. V. V., Ocañas, S. R., Hubbart, C. R., Ko, S., Mondal, S. A., Hense, J. D., Carter, H. N. C., Schneider, A., Kovats, S., Alberola‐Ila, J., et al. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.04.29.538828 · Cited by 8 · see citing works
Self-citationShi, W., Wang, D., Xue, X., Qiao, S., Zhang, W., Shi, J., & Huang, C. Y. (2024) · Journal of Cellular and Molecular Medicine · doi:10.1111/jcmm.70284 · Cited by 8 · see citing works
McCoy, N. D., Gawrys, S. P., Mackintosh, S. G., Byrum, S. D., Kosari, N., Zhou, A., Mansoor, M. A. M., Ikeno, Y., Isola, J. V. V., Stout, M. B., et al. (2025) · GeroScience · doi:10.1007/s11357-025-02019-4 · Cited by 6 · see citing works
Self-citationEffect of senolytic drugs in young female mice chemically induced to estropause
Ávila, B. M., Zanini, B. M., Luduvico, K. P., Oliveira, T. L., Hense, J. D., Garcia, D. N., Prosczek, J. B., Stefanello, F. M., Cruz, P. H. F. D., Giongo, J. L., et al. (2024) · Life Sciences · doi:10.1016/j.lfs.2024.123073 · Cited by 6 · see citing works
Self-citationBezerra, A. F., Alves, J. P. M., Fernandes, C. C. L., Cavalcanti, C. M., Silva, M. R. L., Conde, A. J. H., Tetaping, G. M., Ferreira, A. C. A., Melo, L. M., Rodrigues, A. P. R., et al. (2022) · Veterinary Research Communications · doi:10.1007/s11259-022-09995-4 · Cited by 6 · see citing works
Watson, M. A., Devrukhkar, P. R., Murad, N., Wu, F., Kim, M. J., Anvari, H., Tran, U., Martin, N. G., Tran, T., Zaza, G., et al. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2025.12.03.692228 · Cited by 6 · see citing works
Age-related canine reproductive health
Hanim, M. S. I. C., & Chotimanukul, S. (2025) · Journal of Veterinary Science · doi:10.4142/jvs.25218 · Cited by 5 · see citing works
Reduced fertility induced by MASLD in female mice is improved by senolytic treatment
Hense, J. D., Isola, J. V. V., Garcia, D. N., Zanini, B. M., Prosczek, J. B., Osorio, C. A. P., de Brito, C., Mondal, S. A., Rice, H. C., VAUCHER, R. A., et al. (2026) · Biology of Reproduction · doi:10.1093/biolre/ioag060 · Cited by 5 · see citing works
Self-citationDíaz-Hernández, V., Marmolejo-Valencia, A., la Cruz, C. M.-D., Piñón-Zárate, G., Montaño, L. M., Mora-Herrera, S. I., & Caldelas, I. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25189906 · Cited by 5 · see citing works
Guo, H., Pan, S., Zhao, J., Kong, D.-X., Geng, C.-P., & Miao, S. (2025) · Gynecological Endocrinology · doi:10.1080/09513590.2025.2471549 · Cited by 4 · see citing works
da Silva, A. F. B., de Lima, L. F., Sousa, R. P., da Silva, R. F., da Silva, G. C., de Carvalho, M. A. M., Ferreira, A. C. A., de Oliveira, A. C., Alves, B. G., Rodrigues, A. P. R., et al. (2024) · Reproduction · doi:10.1530/rep-23-0483 · Cited by 4 · see citing works
Wang, Y.-W., Wu, C.-H., Lin, T., & Luo, C. (2021) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2021.111457 · Cited by 4 · see citing works
Timing and duration of calorie restriction determine its impact on ovarian aging in female mice
Prosczek, J. B., Hense, J. D., Garcia, D. N., Sodré, S. P., Blanco, G. A., Osorio, C. A. P., Magalhães, L. S., Pereira, G. C., Zanini, B. M., Ramirez, R. P., et al. (2025) · npj Aging · doi:10.1038/s41514-025-00276-3 · Cited by 4 · see citing works
Self-citationHu, R., Jin, L., Li, Q., Fan, P., Fan, W., & Xu, J. (2026) · Journal of Ovarian Research · doi:10.1186/s13048-026-02040-x · Cited by 3 · see citing works
The problem with one-size-fits-all medicine: biological sex and the aging immune system
Baker, C., Ansere, V. A., Sanqui, C. I., & Benayoun, B. A. (2026) · PLOS Biology · doi:10.1371/journal.pbio.3003763 · Cited by 3 · see citing works
Self-citationThe post-reproductive ovary shifts from a reproductive to an immune-like organ
Converse, A., Dipali, S. S., Schowe, I. P., Kelly, E. B., Jambunathan, S. S., Ocañas, S. R., Stout, M. B., Pritchard, M. T., & Duncan, F. E. (2026) · Molecular Human Reproduction · doi:10.1093/molehr/gaag038 · Cited by 3 · see citing works
Self-citationLima, M., de Sá, N. A. R., Novaes, M. A. S., Palomino, G. J. Q., Tetaping, G. M., Fernandes, C. C. L., Garcia, D. N., Rondina, D., Schneider, A., Figueiredo, J. R., et al. (2023) · Small Ruminant Research · doi:10.1016/j.smallrumres.2023.106985 · Cited by 3 · see citing works
Self-citationŚwigońska, S., Nynca, A., Molcan, T., Petroff, B. K., & Ciereszko, R. E. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms252312538 · Cited by 2 · see citing works
Zhu, Y., Lu, G., Li, W., Su, C., Du, P., Wang, S., Yang, L., Xu, H.-F., Fang, Y., & Song, X. (2025) · Frontiers in Endocrinology · doi:10.3389/fendo.2025.1579031 · Cited by 2 · see citing works
Montenegro, L., Rigos, N., Brandão, C., Pinto, A., Borges, I., Cardoso, L., Carvalho, H., Almeida, H., Martins‐Bessa, A., & Silva, E. (2025) · Frontiers in Aging · doi:10.3389/fragi.2025.1567909 · Cited by 2 · see citing works
Arslan, N. P., AKPINAR, Z., Aybek, H., Doymus, M., Kaldik, G. A., Esim, N., & Taşkın, M. (2025) · Reproductive Toxicology · doi:10.1016/j.reprotox.2025.109067 · Cited by 2 · see citing works
Yang, Y., Rui, B., & Kim, J. H. (2025) · Reproductive Biology and Endocrinology · doi:10.1186/s12958-025-01514-9 · Cited by 2 · see citing works
Single-cell dissection of regulated cell death dynamics in ovarian aging
Zhang, Q., Zhao, Y., Wu, T., Chen, G., Wang, S. X., Li, M., & Zhang, J. (2026) · Journal of Ovarian Research · doi:10.1186/s13048-026-02024-x · Cited by 2 · see citing works
Zhang, G., Du, X., Zhao, Y., Zhi, W., Wang, L., Bai, X., He, L., Xie, H., Liu, J., Han, C., et al. (2026) · Journal of Ovarian Research · doi:10.1186/s13048-026-02076-z · Cited by 2 · see citing works
Mechanistic understanding of female reproductive aging based on the chicken model
Zhang, J., Gao, M., Sun, C., & Yang, N. (2026) · Journal of Animal Science and Biotechnology/Journal of animal science and biotechnology · doi:10.1186/s40104-026-01435-6 · Cited by 2 · see citing works
Harwalkar, K., Yamanaka, N., Pacis, A., Zhao, S., Teng, K., Pitman, W., Taskar, M., Lynn, V., Thornton, A. F., Ford, M. J., et al. (2025) · Aging Cell · doi:10.1111/acel.70051 · Cited by 1 · see citing works
Zamaniyan, M., Peivandi, S., Pashazadeh, M., & Safarloo, F. (2025) · International Journal of Reproductive BioMedicine (IJRM) · doi:10.18502/ijrm.v23i6.19397 · Cited by 1 · see citing works
High-fat and choline-deficient western diets disrupt the ovarian microenvironment in mice
Osorio, C. A. P., Moreira, C. L., Assis, I. L., Magalhães, L. S., Zanini, B. M., Hense, J. D., Garcia, D. N., Prosczek, J. B., Pereira, G. C., Cruz, P. H. F. D., et al. (2026) · Biology of Reproduction · doi:10.1093/biolre/ioag030 · Cited by 1 · see citing works
Self-citationBiological markers of aging across the menopause transition: current evidence
Castaneda, R., Uddenberg, E. R., Andrade, M. D. H., Meek, J. L., Frankhouser, K. N., Faubion, S. S., Chini, E. N., LeBrasseur, N. K., Brar, P., & SHUFELT, C. L. (2026) · Menopause The Journal of The North American Menopause Society · doi:10.1097/gme.0000000000002802 · Cited by 1 · see citing works
Sato, Y., Kawagoe, Y., & Kawamura, K. (2026) · PLoS ONE · doi:10.1371/journal.pone.0348870 · Cited by 1 · see citing works
Pyroptosis in Ovarian Aging, and Its Influence on Female Reproductive Health in Aged Ovaries
Berkel, Ç. (2026) · American Journal of Reproductive Immunology · doi:10.1111/aji.70265 · Cited by 1 · see citing works
Dietary composition and metabolic stress differentially affect the ovarian microenvironment in mice
Pereira, G. C., Pereira, T. H. L., Prosczek, J. B., Magalhães, L. S., Osorio, C. A. P., Nogueira, Â. G. A., Hense, J. D., Zanini, B. M., Garcia, D. N., Mondadori, R. G., et al. (2026) · GeroScience · doi:10.1007/s11357-026-02530-2 · Cited by 1 · see citing works
Self-citationÇAKIR, S. (2022) · Çukurova medical journal (Online)/Çukurova medical journal · doi:10.17826/cumj.1139113 · Cited by 1 · see citing works
Loss of p21 does not protect against premature ovarian insufficiency caused by alkylating agents
Lu, X., Han, Y., Song, J., Wan, Q., Liu, P., Chen, L., Wang, Y., Xue, P., & Dai, X. (2025) · Frontiers in Endocrinology · doi:10.3389/fendo.2025.1616965 · Cited by 1 · see citing works
Liu, Y., Mei, Q., Shen, Q., Yang, J., Zou, M., Li, J., Li, H., Zhang, L., & Xiang, W. (2021) · Research Square · doi:10.21203/rs.3.rs-577307/v1 · Cited by 1 · see citing works
Senchyna, F., Schneider, K., Devrukhkar, P. R., Martin, N., Tran, T., Byrne, J., Watson, M. A., Wu, F., Belić, M., Fuentealba, M., et al. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.02.02.703302 · Cited by 1 · see citing works
Byrne, J., Martin, N., Soygur, B., Watson, M. A., Schneider, K., Schilling, B., & Melov, S. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.05.11.724381 · Cited by 1 · see citing works
Zhang, X., Gunewardena, S., Liu, Y., & Wang, N. (2022) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2022.03.01.481557
Bezerra, A. F., Alves, J. P. M., Fernandes, C. C. L., Cavalcanti, C. M., Silva, M. R. L., Conde, A. J. H., Palomino, G. J. Q., Teixeira, D. Í. A., do Rêgo, A. C., Rodrigues, A. P. R., et al. (2023) · Animal Reproduction · doi:10.1590/1984-3143-ar2023-0019
Palomino, G. J. Q., Celiz, R. H., de Lima, L. F., Ferreira, A. S., Neto, J. E. D. C., Tetaping, G. M., Gomes, F. D. R., Pessoa, O. D. L., Raposo, R. D. S., Rocha, D. D., et al. (2025) · Reproductive Toxicology · doi:10.1016/j.reprotox.2025.108844
Moore, M., Cetinkaya-Un, B., Sarkar, P., Kayisli, U. A., Semerci, N., Teng, M. N., Lockwood, C. J., & Guzeloglu‐Kayisli, O. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26062471
Maged, A. M., Mohsen, R. A., Salah, N., & Ragab, W. S. (2024) · Figshare · doi:10.6084/m9.figshare.26673576
The roles of NF-κB-activated theca cell subtypes in subclinical premature ovarian insufficiency
Chen, P., Chang, Y., Huang, J., Sun, P., Li, M., Liang, X. Y., & Peng, J. (2026) · Reproduction · doi:10.1093/reprod/xaag032
Jin, Y., Sun, W., Jin, X., & Ma, S. (2026) · Open Life Sciences · doi:10.1515/biol-2025-1256
Ovarian aging: Mechanisms and strategies to extend reproductive lifespan
Liu, Y., Wang, Z., Yang, M., Lin, Y., Huo, R., Hu, Z., & Li, J. (2026) · Chinese Medical Journal BioMed · doi:10.65457/cmjbm-2026-0004
Dipali, S. S., & Duncan, F. E. (2026) · Current topics in developmental biology/Current Topics in Developmental Biology · doi:10.1016/bs.ctdb.2026.04.005
Sa, R., Zhang, X., Shi, K., Wang, B., & Yu, H. (2026) · Journal of Ovarian Research · doi:10.1186/s13048-026-02125-7
de Barcelos, S. M., Silva-Carvalho, A. É., Perecin, F., & Carvalho, J. L. (2026) · Molecular Reproduction and Development · doi:10.1002/mrd.70113
Development and Function of Ovarian Lymphatic VasculaturePreprint
Biswas, S., Chen, L., Skalka, J., Xia, L., Srinivasan, R. S., Stout, M. B., & Geng, X. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.05.26.727976
Self-citationShandilya, A., Hajare, S., Arwind, D. A., Giri, C. K., Gajbhiye, R., Ravichandiran, V., & Parihar, V. K. (2026) · Naunyn-Schmiedeberg s Archives of Pharmacology · doi:10.1007/s00210-026-05515-2
The role of IL-33/ST2 signaling in female reproductive diseases
Zhang, N., 唐卯星, Chen, M., & Shi, Y. (2026) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2026.1808099
Wu, H., Yin, X., Zhang, M., Zhong, K., Liang, Y., Wang, Y., Yan, Y., Dong, X., Xu, Y., Yu, H., et al. (2026) · Journal of Ovarian Research · doi:10.1186/s13048-026-02193-9
17α-Estradiol Confers Limited Protection Against APOE4 Phenotypes in Middle-Aged Female MicePreprint
McGill, C. J., Christensen, A., Namvari, S., Thorwald, M. A., Anson, H., Vermulst, M., Finch, C. E., Benayoun, B. A., & Pike, C. J. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.08.06.743074
Mitochondrial Haplotype Shapes the Trajectory of Ovarian Aging in Genetically Heterogeneous Rats
Biswas, S., Nguyen, H. V. M., Converse, A., Matsuzaki, S., Kinter, M. T., Humphries, K. M., Freeman, W. M., Ocañas, S. R., Richardson, A. G., Duncan, F. E., et al. (2026) · Aging Cell · doi:10.1111/acel.70710
Self-citationConserved signaling pathways and transcriptional regulators drive ovarian aging across species
Gao, M., Zhang, J., Yang, J., Gao, S., Yang, N., & Sun, C. (2026) · Poultry Science · doi:10.1016/j.psj.2026.107741
Shirasuna, K., Shirota, A., & Iwata, H. (2026) · Reproductive Medicine and Biology · doi:10.1002/rmb2.70100
Decoding the immune regulation of ovarian aging: mechanisms and therapeutic strategies
Wang, C., Li, N., Chen, Z., Qin, Y., & Jiao, X. (2026) · Human Reproduction Update · doi:10.1093/humupd/dmag030
Gatekeepers of ovarian fate: the molecular landscape of diminished ovarian reserve
Tang, L., Zhou, L., Cui, G., Zhang, J., Hu, H., Lin, R., Jin, Y., Ma, Z., Chai, X., Wang, L., et al. (2026) · Frontiers in Endocrinology · doi:10.3389/fendo.2026.1926422
- Authors
- Ansere, V. A., Ali-Mondal, S., Sathiaseelan, R., Garcia, D. N., Isola, J. V. V., Henseb, J. D., Saccon, T. D., Ocañas, S. R., Tooley, K. B., Stout, M. B., Schneider, A., & Freeman, W. M.
- Affiliations
- University of Oklahoma Health Sciences Center (US)
- Universidade Federal de Pelotas (BR)
- Oklahoma Medical Research Foundation (US)
- Corresponding author
- Freeman, Willard M.
- ORCID
- Venue
- Mechanisms of Ageing and Development
- Publisher
- Elsevier BV
- Published
- 2021-03
- Volume
- 194
- Pages
- 111425
- ISSN
- 0047-6374 (ISSN-L)
- PMC
- PMC8279026
- OpenAlex
- W3117460981
- Cited by
- 101
- References
- 93
- Citations by year
- 2026: 31 · 2025: 22 · 2024: 23 · 2023: 10 · 2022: 12 · 2021: 3
- FWCI
- 4.68
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Mechanisms of Ageing and Development (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- American Foundation for Aging Research
- Conselho Nacional de Desenvolvimento Científico e Tecnológico
- National Institute on Aging
- Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
- Topics
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Reproductive Biology and Fertility
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Keywords
- ovarian aging, cellular senescence, ovarian reserve, primordial follicle depletion, DNA methylation, hydroxymethylation, epigenetics, transcriptomics, oxidative bisulfite sequencing, p21, CDKN2A, plasminogen activator inhibitor-1, HMGB1, inflammation, cell cycle inhibition, mouse model
- MeSH terms
- Age Factors, Aging, Animals, Female, Ovarian Follicle, Mice, Inbred C57BL, Ovary, Cytokines, Primary Ovarian Insufficiency, Cellular Senescence, Cell Cycle Proteins, Inflammation Mediators, DNA Methylation, Gene Expression Profiling, Epigenesis, Genetic, Mice, Transcriptome, Ovarian Reserve
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
