{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T19:10:31Z","timestamp":1789153831784,"version":"build-2803163510"},"posted":{"date-parts":[[2026,9,8]]},"group-title":"Genomics","reference-count":57,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T00:00:00Z","timestamp":1788825600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000057","name":"NIGMS","doi-asserted-by":"crossref","award":["R35 GM142395"],"award-info":[{"award-number":["R35 GM142395"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"crossref"}]},{"name":"NIA","award":["T32 AG052374"],"award-info":[{"award-number":["T32 AG052374"]}]},{"name":"NIA","award":["P30 AG068345"],"award-info":[{"award-number":["P30 AG068345"]}]},{"name":"NIH OD","award":["S10 OD028654"],"award-info":[{"award-number":["S10 OD028654"]}]},{"name":"NSF","award":["DGE-1842487"],"award-info":[{"award-number":["DGE-1842487"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,9,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  A large portion of eukaryotic genomes is composed of transposable elements, which are usually kept repressed in young, healthy cells but can be derepressed in response to cell senescence and organismal aging.\n                  <jats:italic>LINE-1 (L1)<\/jats:italic>\n                  is the most abundant TE in the human genome by percent coverage, and its derepression has been implicated in inflammaging responses. However, whether\n                  <jats:italic>L1<\/jats:italic>\n                  transcription itself is sufficient to drive aging-associated molecular phenotypes in healthy cells has not been extensively explored. Here, we leverage a multi-omic approach combining transcriptomics, proteomics, and secretomics of primary human IMR-90 fibroblasts transiently overexpressing a human\n                  <jats:italic>L1Hs<\/jats:italic>\n                  element in order to define the systems-level consequences of\n                  <jats:italic>L1<\/jats:italic>\n                  transcription. Intriguingly, transient\n                  <jats:italic>L1Hs<\/jats:italic>\n                  overexpression induced widespread remodeling of the transcriptome, proteome and secretome, impacting pathways related to cell cycle regulation and interferon signaling. Interrogation of multiple independent\n                  <jats:italic>L1<\/jats:italic>\n                  elements revealed both shared and distinct cellular responses to acute expression. Thus, our findings demonstrate that acute\n                  <jats:italic>L1<\/jats:italic>\n                  expression induces coordinated molecular remodeling extending beyond canonical retrotransposition-associated pathways, rather than simply mimicking senescence or triggering antiviral signaling. This study establishes a comprehensive multi-omics resource for investigating the impact of\n                  <jats:italic>L1<\/jats:italic>\n                  transcription in human cells and highlights the need to consider individual transposable element families as distinct regulators of cellular state during aging and disease.\n                <\/jats:p>","DOI":"10.64898\/2026.09.03.749265","type":"posted-content","created":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T20:20:11Z","timestamp":1788898811000},"source":"Crossref","is-referenced-by-count":0,"title":["Acute\n                  <i>LINE-1<\/i>\n                  overexpression rewires the transcriptome, proteome and secretome of primary human fibroblasts"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9429-0488","authenticated-orcid":false,"given":"Juan I.","family":"Bravo","sequence":"first","affiliation":[{"name":"Leonard Davis School of Gerontology, University of Southern California, Los Angeles, CA 90089, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-6073-3711","authenticated-orcid":false,"given":"Eyael","family":"Tewelde","sequence":"additional","affiliation":[{"name":"Leonard Davis School of Gerontology, University of Southern California, Los Angeles, CA 90089, USA"},{"name":"Alfred E. Mann School of Pharmacy and Pharmaceutical Sciences, University of Southern California, Los Angeles, CA 90033, USA"},{"name":"Graduate program in Pharmaceutical and Translational Sciences, University of Southern California, Los Angeles, CA 90033, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina D.","family":"King","sequence":"additional","affiliation":[{"name":"Buck Institute for Research on Aging, Novato, CA 94945, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nayana S.","family":"Tellakula","sequence":"additional","affiliation":[{"name":"Leonard Davis School of Gerontology, University of Southern California, Los Angeles, CA 90089, USA"},{"name":"Cancer Biology Department, USC Keck School of Medicine, Los Angeles, CA 90033, USA"},{"name":"Graduate program in Cancer Genomics and Bioinformatics, University of Southern California, Los Angeles, CA 90033, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9907-2749","authenticated-orcid":false,"given":"Birgit","family":"Schilling","sequence":"additional","affiliation":[{"name":"Buck Institute for Research on Aging, Novato, CA 94945, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7401-4777","authenticated-orcid":false,"given":"B\u00e9r\u00e9nice A.","family":"Benayoun","sequence":"additional","affiliation":[{"name":"Leonard Davis School of Gerontology, University of Southern California, Los Angeles, CA 90089, USA"},{"name":"Alfred E. Mann School of Pharmacy and Pharmaceutical Sciences, University of Southern California, Los Angeles, CA 90033, USA"},{"name":"Cancer Biology Department, USC Keck School of Medicine, Los Angeles, CA 90033, USA"},{"name":"USC Norris Comprehensive Cancer Center, Epigenetics and Gene Regulation, Los Angeles, CA 90033, USA"},{"name":"USC Stem Cell Initiative, Los Angeles, CA 90089, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026091111552312000_2026.09.03.749265v1.1","unstructured":"Lander ES, L.L. , Birren B , Nusbaum C , Zody MC , Baldwin J , Devon K , Dewar K , Doyle M , FitzHugh W , Funke R , Gage D , Harris K , Heaford A , Howland J , Kann L , Lehoczky J , LeVine R , McEwan P , McKernan K , Meldrim J , Mesirov JP , Miranda C , Morris W , Naylor J , Raymond C , Rosetti M , Santos R , Sheridan A , Sougnez C , Stange-Thomann Y , Stojanovic N , Subramanian A , Wyman D , Rogers J , Sulston J , Ainscough R , Beck S , Bentley D , Burton J , Clee C , Carter N , Coulson A , Deadman R , Deloukas P , Dunham A , Dunham I , Durbin R , French L , Grafham D , Gregory S , Hubbard T , Humphray S , Hunt A , Jones M , Lloyd C , McMurray A , Matthews L , Mercer S , Milne S , Mullikin JC , Mungall A , Plumb R , Ross M , Shownkeen R , Sims S , Waterston RH , Wilson RK , Hillier LW , McPherson JD , Marra MA , Mardis ER , Fulton LA , Chinwalla AT , Pepin KH , Gish WR , Chissoe SL , Wendl MC , Delehaunty KD , Miner TL , Delehaunty A , Kramer JB , Cook LL , Fulton RS , Johnson DL , Minx PJ , Clifton SW , Hawkins T , Branscomb E , Predki P , Richardson P , Wenning S , Slezak T , Doggett N , Cheng JF , Olsen A , Lucas S , Elkin C , Uberbacher E , Frazier M , Gibbs RA , Muzny DM , Scherer SE , Bouck JB , Sodergren EJ , Worley KC , Rives CM , Gorrell JH , Metzker ML , Naylor SL , Kucherlapati RS , Nelson DL , Weinstock GM , Sakaki Y , Fujiyama A , Hattori M , Yada T , Toyoda A , Itoh T , Kawagoe C , Watanabe H , Totoki Y , Taylor T , Weissenbach J , Heilig R , Saurin W , Artiguenave F , Brottier P , Bruls T , Pelletier E , Robert C , Wincker P , Smith DR , Doucette-Stamm L , Rubenfield M , Weinstock K , Lee HM , Dubois J , Rosenthal A , Platzer M , Nyakatura G , Taudien S , Rump A , Yang H , Yu J , Wang J , Huang G , Gu J , Hood L , Rowen L , Madan A , Qin S , Davis RW , Federspiel NA , Abola AP , Proctor MJ , Myers RM , Schmutz J , Dickson M , Grimwood J , Cox DR , Olson MV , Kaul R , Raymond C , Shimizu N , Kawasaki K , Minoshima S , Evans GA , Athanasiou M , Schultz R , Roe BA , Chen F , Pan H , Ramser J , Lehrach H , Reinhardt R , McCombie WR , de la Bastide M , Dedhia N , Bl\u00f6cker H , Hornischer K , Nordsiek G , Agarwala R , Aravind L , Bailey JA , Bateman A , Batzoglou S , Birney E , Bork P , Brown DG , Burge CB , Cerutti L , Chen HC , Church D , Clamp M , Copley RR , Doerks T , Eddy SR , Eichler EE , Furey TS , Galagan J , Gilbert JG , Harmon C , Hayashizaki Y , Haussler D , Hermjakob H , Hokamp K , Jang W , Johnson LS , Jones TA , Kasif S , Kaspryzk A , Kennedy S , Kent WJ , Kitts P , Koonin EV , Korf I , Kulp D , Lancet D , Lowe TM , McLysaght A , Mikkelsen T , Moran JV , Mulder N , Pollara VJ , Ponting CP , Schuler G , Schultz J , Slater G , Smit AF , Stupka E , Szustakowki J , Thierry-Mieg D , Thierry-Mieg J , Wagner L , Wallis J , Wheeler R , Williams A , Wolf YI , Wolfe KH , Yang SP , Yeh RF , Collins F , Guyer MS , Peterson J , Felsenfeld A , Wetterstrand KA , Patrinos A , Morgan MJ , de Jong P , Catanese JJ , Osoegawa K , Shizuya H , Choi S , Chen YJ , Szustakowki J ; International Human Genome Sequencing Consortium, Initial sequencing and analysis of the human genome . 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