{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T00:42:53Z","timestamp":1787013773714,"version":"build-2736575974"},"reference-count":22,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2025,11,17]],"date-time":"2025-11-17T00:00:00Z","timestamp":1763337600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,11,17]],"date-time":"2025-11-17T00:00:00Z","timestamp":1763337600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32260148"],"award-info":[{"award-number":["32260148"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31900410"],"award-info":[{"award-number":["31900410"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Aging Cell"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Despite the long interspersed nuclear element\u20101 (LINE1, L1) retrotransposons having been implicated in Alzheimer's disease (AD), a fundamental understanding of the AD\u2010specific lifespan\u2010long trajectory of L1 has been limited. Here, we characterize the content and expression of L1 covering four brain regions (hippocampus, prefrontal cortex, cerebellum, and the rest of brain tissue) of APP\/PS1 mice, a murine model of AD, and their wild\u2010type C57BL\/6 littermates from 3 to 24\u2009months of age. We report that both L1 content (indicated by DNA copy number) and expression (indicated by protein levels of L1\u2010encoded ORF1 and ORF2) across brain regions had nonlinear, U\u2010shaped associations with age in wild\u2010type and APP\/PS1 mice. Compared to age\u2010matched wild\u2010types, APP\/PS1 mice constantly have significantly decreased L1 content but increased L1 expression, suggesting L1 differences between wild\u2010type and APP\/PS1 mice establish early and remain stable throughout the life course. Strikingly, L1 content and expression in wild\u2010type and APP\/PS1 mice are sexually different, depending on age and brain region. The appearance of L1 alteration precedes the onset of \u03b2\u2010amyloidosis by 3\u2009months in APP\/PS1 mice, and \u03b2\u2010amyloidosis is positively correlated with L1 content and expression in males but anti\u2010correlated with L1 content in females of both wild\u2010type and APP\/PS1 mice. Overall, this study (i) reveals an unanticipated U\u2010shaped trajectory of L1 content and expression in both normal and pathological aging of mouse brains and (ii) discerns specific changes in L1 content and expression tied to AD neuropathology in a sex\u2010different manner.<\/jats:p>","DOI":"10.1111\/acel.70296","type":"journal-article","created":{"date-parts":[[2025,11,17]],"date-time":"2025-11-17T08:23:11Z","timestamp":1763367791000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Unveiling Aging and Alzheimer's Disease\u2013Associated Dynamics of\n                    <scp>LINE1 DNA<\/scp>\n                    Content and Protein Expression in Mouse Brains"],"prefix":"10.1111","volume":"24","author":[{"given":"Minyan","family":"Jiang","sequence":"first","affiliation":[{"name":"School of Life Sciences Yunnan Normal University  Kunming Yunnan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Life Sciences Yunnan Normal University  Kunming Yunnan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juanlin","family":"Chen","sequence":"additional","affiliation":[{"name":"School of Life Sciences Yunnan Normal University  Kunming Yunnan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanmei","family":"Qi","sequence":"additional","affiliation":[{"name":"School of Life Sciences Yunnan Normal University  Kunming Yunnan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lina","family":"Zhu","sequence":"additional","affiliation":[{"name":"School of Life Sciences Yunnan Normal University  Kunming Yunnan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zetong","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Life Sciences Yunnan Normal University  Kunming Yunnan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianfei","family":"Li","sequence":"additional","affiliation":[{"name":"School of Life Sciences Yunnan Normal University  Kunming Yunnan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Zhou","sequence":"additional","affiliation":[{"name":"School of Life Sciences Yunnan Normal University  Kunming Yunnan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8453-1842","authenticated-orcid":false,"given":"Xu","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Life Sciences Yunnan Normal University  Kunming Yunnan China"},{"name":"Yeda Institute of Gene and Cell Therapy  Taizhou Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7911-1640","authenticated-orcid":false,"given":"Xihan","family":"Guo","sequence":"additional","affiliation":[{"name":"School of Life Sciences Yunnan Normal University  Kunming Yunnan China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,11,17]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.abi6087"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010021\u201082953\u20103"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2020.147123"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.18632\/aging.100621"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tig.2017.07.004"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.14164"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2021.743797"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abj3658"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells11010079"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2018.05.004"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11357\u2010024\u201001468\u20107"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00439\u2010020\u201002114\u2010w"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/acel.14121"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010021\u201022129\u20109"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11357\u2010022\u201000580\u2010w"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2298\u201024.2025"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2018.05.043"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkr863"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401\u2010024\u201002835\u20106"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkab369"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1011668"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41422\u2010021\u201000515\u20108"}],"container-title":["Aging Cell"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/acel.70296","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/acel.70296","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/acel.70296","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T03:27:43Z","timestamp":1780457263000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/acel.70296"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,17]]},"references-count":22,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2025,12]]}},"alternative-id":["10.1111\/acel.70296"],"URL":"https:\/\/doi.org\/10.1111\/acel.70296","archive":["Portico"],"relation":{},"ISSN":["1474-9718","1474-9726"],"issn-type":[{"value":"1474-9718","type":"print"},{"value":"1474-9726","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,17]]},"assertion":[{"value":"2025-09-06","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-10-29","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-11-17","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70296"}}