{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T14:47:17Z","timestamp":1787323637060,"version":"build-2736575974"},"reference-count":51,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2026,8,9]],"date-time":"2026-08-09T00:00:00Z","timestamp":1786233600000},"content-version":"vor","delay-in-days":8,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01AG075589"],"award-info":[{"award-number":["R01AG075589"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100001384","name":"Samuel Waxman Cancer Research Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100001384","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Aging Cell"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>The incidence of breast cancer shows its largest peak around the age of 65 but also a peak around 45 indicating a bimodal distribution. While some potential explanations, such as age\u2010related enrichment in specific breast cancer sub\u2010types and BRCA1\/2 mutations were proposed, they do not explain why the peaks are at 45 and 65, raising the possibility that the way the breast ages may play a role. Here using two mouse models, we show two distinct aging patterns of the mammary gland; one being progressive, the other bimodal. In the bimodal model, waves of overlapping genes and proteins associated with breast cancer pathways are observed at 11 and 19\u2009months but are absent at 3 and 14\u2009months. Further, in the bimodal model, the mammary glands at 11 and 19\u2009months are more permissive to the growth of cancer cells but not at 14 or &gt;\u200922\u2009months, while in the progressive model, the growth of cancer cells increases starting at 14\u2009months of age. Using scRNAseq, we established a bimodal aging signature. Since 11 and 19\u2009months in mice correlate with 45 and 65 in humans, we tested the mammary gland\u2010derived bimodal signature in two breast cancer databases and found that the signature is enriched in women diagnosed at 45 and 65. Therefore, our study raises the possibility that distinct patterns of aging of the breast exist and that they may contribute to the bimodal distribution of breast cancer. Further, our study adds to the growing evidence of non\u2010linear aging.<\/jats:p>","DOI":"10.1111\/acel.70661","type":"journal-article","created":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T03:42:31Z","timestamp":1786333351000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Mitochondria Dictate Progressive Versus Bimodal Aging of the Mammary Gland"],"prefix":"10.1111","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6448-090X","authenticated-orcid":false,"given":"Edmund Charles","family":"Jenkins","sequence":"first","affiliation":[{"name":"Division of Hematology\/Oncology, Department of Medicine Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mrittika","family":"Chattopadhyay","sequence":"additional","affiliation":[{"name":"Division of Hematology\/Oncology, Department of Medicine Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thelma","family":"Mashaka","sequence":"additional","affiliation":[{"name":"Division of Hematology\/Oncology, Department of Medicine Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miguel","family":"Torres\u2010Martin","sequence":"additional","affiliation":[{"name":"Center for Genomic Regulation, Barcelona Institute of Science and Technology  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Sia","sequence":"additional","affiliation":[{"name":"Division of Liver Diseases, Department of Medicine Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Igor","family":"Bado","sequence":"additional","affiliation":[{"name":"Department of Oncological Sciences Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6597-0196","authenticated-orcid":false,"given":"Doris","family":"Germain","sequence":"additional","affiliation":[{"name":"Division of Hematology\/Oncology, Department of Medicine Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,9]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10549\u2010019\u201005442\u20102"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tcb.2020.03.001"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1158\/1055\u20109965.EPI\u201006\u20100191"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202100128"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008\u20105472.CAN\u201006\u20103554"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2005.02.001"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.critrevonc.2007.09.001"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1210\/endo.141.8.7609"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI64125"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008\u20105472.CAN\u201005\u20101428"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2021.02.011"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2022.929708"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010025\u201061666\u20105"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2017.05.028"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aat5314"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10038\u2010008\u20100331\u2010x"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12094\u2010016\u20101561\u20106"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10549\u2010023\u201006946\u20108"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2022.111124"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.4161\/cc.4.11.2121"},{"issue":"22","key":"e_1_2_10_22_1","first-page":"6052","article-title":"Direct Action of 17 Beta\u2010Estradiol on Mouse Mammary Ducts Analyzed by Sustained Release Implants and Steroid Autoradiography","volume":"47","author":"Daniel C. 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