{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,18]],"date-time":"2026-10-18T11:59:56Z","timestamp":1792324796119,"version":"4.4.0"},"reference-count":103,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T00:00:00Z","timestamp":1788480000000},"content-version":"vor","delay-in-days":3,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","award":["2023\/11499\u20108"],"award-info":[{"award-number":["2023\/11499\u20108"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","award":["2017\/19541\u20102"],"award-info":[{"award-number":["2017\/19541\u20102"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","award":["2020\/14158\u20109"],"award-info":[{"award-number":["2020\/14158\u20109"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","award":["2018\/15579\u20108"],"award-info":[{"award-number":["2018\/15579\u20108"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100013275","name":"Instituto Serrapilheira","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100013275","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"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Aging Cell"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Although aging and cancer share complex molecular mechanisms, distinguishing causative factors from byproducts remains challenging. Here, we investigated the role of tissue transcriptomic entropy\u2014a measure of transcriptional disorder\u2014in aging and cancer processes by analyzing RNA\u2010sequencing data from over 25,000 samples from human and mouse tissues. We found that entropy changes during aging are highly tissue\u2010specific, with some tissues showing increased entropy while others exhibit decreased or stable entropy levels. Moreover, transcriptomic entropy strongly correlates with age\u2010related processes, showing positive associations with proliferation, cellular senescence, somatic mutation burden, and cellular reprogramming, whereas it negatively correlates with stemness. In cancer, we observed that primary tumors generally display higher entropy than normal tissue, with its levels further increasing in metastatic stages. Cancer treatment modulated entropy patterns in multiple contexts, with changes suggesting a role for transcriptional complexity in tumor plasticity and therapy resistance. Elevated entropy levels predicted poor survival outcomes in multiple cancer types, suggesting its potential as a prognostic marker. Furthermore, differential expression analysis revealed that entropy\u2010associated genes are enriched in developmental processes and depleted in metabolic pathways, indicating a possible link to cellular dedifferentiation. Finally, we found increased entropy in various age\u2010related disorders beyond cancer, suggesting that transcriptomic entropy may be a common feature in age\u2010related diseases. Our findings establish transcriptomic entropy as a fundamental parameter in aging and cancer progression, offering new insights into disease mechanisms.<\/jats:p>","DOI":"10.1111\/acel.70696","type":"journal-article","created":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T11:37:43Z","timestamp":1788521863000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Tissue\u2010Level Transcriptomic Entropy Reveals Organ\u2010Specific Aging Patterns and Predicts Cancer Progression"],"prefix":"10.1111","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1602-9193","authenticated-orcid":false,"given":"Gabriel Arantes","family":"dos Santos","sequence":"first","affiliation":[{"name":"Hospital S\u00edrio\u2010Liban\u00eas  S\u00e3o Paulo SP Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2627-5331","authenticated-orcid":false,"given":"Jos\u00e9 Pedro","family":"Castro","sequence":"additional","affiliation":[{"name":"i3S, Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade Universidade do Porto  Porto Portugal"},{"name":"Aging and Aneuploidy Laboratory, Instituto de Biologia Molecular e Celular Universidade do Porto  Porto Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1789-2768","authenticated-orcid":false,"given":"Gabriela D. A.","family":"Guardia","sequence":"additional","affiliation":[{"name":"Hospital S\u00edrio\u2010Liban\u00eas  S\u00e3o Paulo SP Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2335-463X","authenticated-orcid":false,"given":"Filipe F.","family":"dos Santos","sequence":"additional","affiliation":[{"name":"Hospital S\u00edrio\u2010Liban\u00eas  S\u00e3o Paulo SP Brazil"},{"name":"Department of Biochemistry, Instituto de Quimica Universidade de Sao Paulo  S\u00e3o Paulo SP Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1015-2561","authenticated-orcid":false,"given":"Alexander","family":"Birbrair","sequence":"additional","affiliation":[{"name":"University of Wisconsin\u2010Madison  Madison Wisconsin USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4820-4155","authenticated-orcid":false,"given":"Pedro A. F.","family":"Galante","sequence":"additional","affiliation":[{"name":"Hospital S\u00edrio\u2010Liban\u00eas  S\u00e3o Paulo SP Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,4]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.3390\/biology12111396"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaz1776"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1101\/2024.09.06.611669v1"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-017-01027-z"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1101\/2024.10.03.616489"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep03039"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1004115"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcsm.13846"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/acel.14056"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2022.1051539"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/bies.202000140"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-1338-5"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12943-021-01326-6"},{"key":"e_1_2_12_15_1","first-page":"685","article-title":"DNA Methylation Entropy Is a Biomarker for Aging","volume":"17","author":"Chan J.","year":"2025","journal-title":"Aging (Albany NY)"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2024.102268"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.trecan.2022.06.007"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/acel.13041"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.3233\/JPD-212834"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkad965"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2019.00930"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbabio.2017.02.001"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-23-0816"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkad927"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/bies.20760"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12864-023-09756-w"},{"key":"e_1_2_12_27_1","first-page":"5796","article-title":"Evidence of a Pan\u2010Tissue Decline in Stemness During Human Aging","volume":"16","author":"Santos G. A.","year":"2024","journal-title":"Aging"},{"key":"e_1_2_12_28_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.abl4290"},{"key":"e_1_2_12_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41568-019-0156-2"},{"key":"e_1_2_12_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-017-02772-x"},{"key":"e_1_2_12_31_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-019-1919-5"},{"key":"e_1_2_12_32_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btz931"},{"key":"e_1_2_12_33_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-physiol-030212-183712"},{"key":"e_1_2_12_34_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.71624"},{"key":"e_1_2_12_35_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22115814"},{"key":"e_1_2_12_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-03542-y"},{"key":"e_1_2_12_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2016.05.010"},{"key":"e_1_2_12_38_1","doi-asserted-by":"publisher","DOI":"10.1101\/gr.280304.124"},{"key":"e_1_2_12_39_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aax0249"},{"key":"e_1_2_12_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-022-01251-0"},{"key":"e_1_2_12_41_1","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-21-1059"},{"key":"e_1_2_12_42_1","doi-asserted-by":"publisher","DOI":"10.3390\/genes14030558"},{"key":"e_1_2_12_43_1","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2013-14-10-r115"},{"key":"e_1_2_12_44_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.80380"},{"key":"e_1_2_12_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2023.106368"},{"key":"e_1_2_12_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2018.09.006"},{"key":"e_1_2_12_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2018.11.002"},{"key":"e_1_2_12_48_1","doi-asserted-by":"publisher","DOI":"10.1258\/ebm.2011.011007"},{"key":"e_1_2_12_49_1","doi-asserted-by":"publisher","DOI":"10.1093\/bfgp\/elad019"},{"key":"e_1_2_12_50_1","volume-title":"Ggpubr: \u201cGgplot2\u201d Based Publication Ready Plots. CRAN: Contributed Packages","author":"Kassambara A.","year":"2016"},{"key":"e_1_2_12_51_1","volume-title":"Survminer: Drawing Survival Curves Using \u201cGgplot2.\u201d CRAN: Contributed Packages","author":"Kassambara A.","year":"2016"},{"key":"e_1_2_12_52_1","volume-title":"Pheatmap: Pretty Heatmaps. CRAN: Contributed Packages","author":"Kolde R.","year":"2010"},{"key":"e_1_2_12_53_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00061.2017"},{"key":"e_1_2_12_54_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41556-018-0249-2"},{"key":"e_1_2_12_55_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12979-017-0112-5"},{"key":"e_1_2_12_56_1","doi-asserted-by":"publisher","DOI":"10.1111\/acel.70164"},{"key":"e_1_2_12_57_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2018.02.052"},{"key":"e_1_2_12_58_1","doi-asserted-by":"publisher","DOI":"10.15252\/embj.2022112740"},{"key":"e_1_2_12_59_1","doi-asserted-by":"publisher","DOI":"10.1093\/bib\/bbae698"},{"key":"e_1_2_12_60_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2022.11.001"},{"key":"e_1_2_12_61_1","doi-asserted-by":"publisher","DOI":"10.1093\/bfgp\/elab009"},{"key":"e_1_2_12_62_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-32283-3"},{"key":"e_1_2_12_63_1","doi-asserted-by":"publisher","DOI":"10.1038\/s43587-023-00527-6"},{"key":"e_1_2_12_64_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2024.10.019"},{"key":"e_1_2_12_65_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-023-01627-0"},{"key":"e_1_2_12_66_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2018.03.034"},{"key":"e_1_2_12_67_1","doi-asserted-by":"publisher","DOI":"10.1101\/gr.277491.122"},{"key":"e_1_2_12_68_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11357-024-01191-3"},{"key":"e_1_2_12_69_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mad.2019.111177"},{"key":"e_1_2_12_70_1","doi-asserted-by":"publisher","DOI":"10.1038\/s43587-024-00619-x"},{"key":"e_1_2_12_71_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-019-0114-2"},{"key":"e_1_2_12_72_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10522-024-10138-2"},{"key":"e_1_2_12_73_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.conb.2020.05.001"},{"key":"e_1_2_12_74_1","doi-asserted-by":"publisher","DOI":"10.1214\/16-AOAS920"},{"key":"e_1_2_12_75_1","doi-asserted-by":"publisher","DOI":"10.4161\/15384101.2014.973327"},{"key":"e_1_2_12_76_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.16961"},{"key":"e_1_2_12_77_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0237006"},{"key":"e_1_2_12_78_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exger.2014.03.015"},{"key":"e_1_2_12_79_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkv007"},{"key":"e_1_2_12_80_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-32552-1"},{"key":"e_1_2_12_81_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13148-021-01158-7"},{"key":"e_1_2_12_82_1","volume-title":"Ggrepel: Automatically Position Non\u2010Overlapping Text Labels With \u201cGgplot2.\u201d CRAN: Contributed Packages","author":"Slowikowski K.","year":"2016"},{"key":"e_1_2_12_83_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10555-013-9431-y"},{"key":"e_1_2_12_84_1","doi-asserted-by":"publisher","DOI":"10.1038\/s43587-024-00616-0"},{"key":"e_1_2_12_85_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms15599"},{"key":"e_1_2_12_86_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41576-021-00341-z"},{"key":"e_1_2_12_87_1","doi-asserted-by":"publisher","DOI":"10.1038\/s43587\u2010022\u201000231\u2010x"},{"key":"e_1_2_12_88_1","volume-title":"Modeling Survival Data: Extending the Cox Model","author":"Therneau T. M.","year":"2013"},{"key":"e_1_2_12_89_1","doi-asserted-by":"publisher","DOI":"10.1038\/s43587-024-00600-8"},{"key":"e_1_2_12_90_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-026-10542-3"},{"key":"e_1_2_12_91_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2023.05.002"},{"key":"e_1_2_12_92_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-023-02866-4"},{"key":"e_1_2_12_93_1","doi-asserted-by":"publisher","DOI":"10.3389\/freae.2024.1423454"},{"key":"e_1_2_12_94_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1002240"},{"key":"e_1_2_12_95_1","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-13-0631"},{"key":"e_1_2_12_96_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-022-01211-8"},{"key":"e_1_2_12_97_1","volume-title":"Corrplot: Visualization of a Correlation Matrix. CRAN: Contributed Packages","author":"Wei T.","year":"2010"},{"key":"e_1_2_12_98_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-0-387-98141-3"},{"key":"e_1_2_12_99_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mad.2021.111583"},{"key":"e_1_2_12_100_1","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2013.00019"},{"key":"e_1_2_12_101_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13402-022-00707-3"},{"key":"e_1_2_12_102_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2022.12.027"},{"key":"e_1_2_12_103_1","doi-asserted-by":"publisher","DOI":"10.1101\/gr.278144.123"},{"key":"e_1_2_12_104_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-32567-8"}],"container-title":["Aging Cell"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/acel.70696","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/acel.70696","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/acel.70696","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T05:07:38Z","timestamp":1790572058000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/acel.70696"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9]]},"references-count":103,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2026,9]]}},"alternative-id":["10.1111\/acel.70696"],"URL":"https:\/\/doi.org\/10.1111\/acel.70696","archive":["Portico"],"relation":{},"ISSN":["1474-9718","1474-9726"],"issn-type":[{"value":"1474-9718","type":"print"},{"value":"1474-9726","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9]]},"assertion":[{"value":"2026-04-09","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-24","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-04","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70696"}}