{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T08:00:03Z","timestamp":1780646403262,"version":"3.54.1"},"reference-count":28,"publisher":"Oxford University Press (OUP)","license":[{"start":{"date-parts":[[2023,10,6]],"date-time":"2023-10-06T00:00:00Z","timestamp":1696550400000},"content-version":"vor","delay-in-days":278,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81971715 82070527 U21A20391"],"award-info":[{"award-number":["81971715 82070527 U21A20391"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Shenzhen Natural Science Fund Committee","award":["JCYJ20190807145015194"],"award-info":[{"award-number":["JCYJ20190807145015194"]}]},{"name":"Applied Technology Research and Development Plan of Heilongjiang Province","award":["GY2020YF0039"],"award-info":[{"award-number":["GY2020YF0039"]}]},{"name":"HMU Marshal Initiative Funding","award":["HMUMIF-21020"],"award-info":[{"award-number":["HMUMIF-21020"]}]},{"name":"Key Laboratory of Emergency and Trauma of Ministry of Education","award":["KLET-202117"],"award-info":[{"award-number":["KLET-202117"]}]},{"DOI":"10.13039\/501100012166","name":"National Key R&D Program of China","doi-asserted-by":"publisher","award":["2020YFC2005000"],"award-info":[{"award-number":["2020YFC2005000"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004806","name":"Fok Ying-Tong Education Foundation","doi-asserted-by":"crossref","award":["171032"],"award-info":[{"award-number":["171032"]}],"id":[{"id":"10.13039\/501100004806","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81971715 82070527 U21A20391"],"award-info":[{"award-number":["81971715 82070527 U21A20391"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Shenzhen Natural Science Fund Committee","award":["JCYJ20190807145015194"],"award-info":[{"award-number":["JCYJ20190807145015194"]}]},{"name":"Applied Technology Research and Development Plan of Heilongjiang Province","award":["GY2020YF0039"],"award-info":[{"award-number":["GY2020YF0039"]}]},{"name":"HMU Marshal Initiative Funding","award":["HMUMIF-21020"],"award-info":[{"award-number":["HMUMIF-21020"]}]},{"name":"Key Laboratory of Emergency and Trauma of Ministry of Education","award":["KLET-202117"],"award-info":[{"award-number":["KLET-202117"]}]},{"DOI":"10.13039\/501100012166","name":"National Key R&D Program of China","doi-asserted-by":"publisher","award":["2020YFC2005000"],"award-info":[{"award-number":["2020YFC2005000"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004806","name":"Fok Ying-Tong Education Foundation","doi-asserted-by":"crossref","award":["171032"],"award-info":[{"award-number":["171032"]}],"id":[{"id":"10.13039\/501100004806","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,10,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Aging and cellular senescence are characterized by a progressive loss of physiological integrity, which could be triggered by aging factors such as physiological, pathological and external factors. Numerous studies have shown that gene regulatory events play crucial roles in aging, increasing the need for a comprehensive repository of regulatory relationships during aging. Here, we established a manually curated database of aging factors (AgingReG, https:\/\/bio.liclab.net\/Aging-ReG\/), focusing on the regulatory relationships during aging with experimental evidence in humans. By curating thousands of published literature, 2157 aging factor entries (1345 aging gene entries, 804 external factor entries and eight aging-related pathway entries) and related regulatory information were manually curated. The regulatory relationships were classified into four types according to their functions: (i) upregulation, which indicates that aging factors upregulate the expression of target genes during aging; (ii) downregulation, which indicates that aging factors downregulate the expression of target genes during aging; (iii) activation, which indicates that aging factors influence the activity of target genes during aging and (iv) inhibition, which indicates that aging factors inhibit the activation of target molecule activity, leading to declined or lost target activity. AgingReG involves 651 upregulating pairs, 632 downregulating pairs, 330 activation-regulating pairs and 34 inhibition-regulating pairs, covering 195 disease types and more than 800 kinds of cells and tissues from 1784 published literature studies. AgingReG provides a user-friendly interface to query, browse and visualize detailed information about the regulatory relationships during aging. We believe that AgingReG will serve as a valuable resource database in the field of aging research.<\/jats:p>\n               <jats:p>Database URL: https:\/\/bio.liclab.net\/Aging-ReG\/<\/jats:p>","DOI":"10.1093\/database\/baad064","type":"journal-article","created":{"date-parts":[[2023,10,6]],"date-time":"2023-10-06T19:38:12Z","timestamp":1696621092000},"source":"Crossref","is-referenced-by-count":3,"title":["AgingReG: a curated database of\u00a0aging regulatory relationships in\u00a0humans"],"prefix":"10.1093","volume":"2023","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1032-4856","authenticated-orcid":false,"given":"Minghui","family":"Piao","sequence":"first","affiliation":[{"name":"Department of Cardiology, The Second Affiliated Hospital of Harbin Medical University , No. 246 Xuefu Road, Nangang District, Harbin 150086, China"},{"name":"The Key Laboratory of Myocardial Ischemia, Harbin Medical University, Ministry of Education , No. 246 Xuefu Road, Nangang District, Harbin 150086, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ke","family":"Feng","sequence":"additional","affiliation":[{"name":"College of Bioinformatics Science and Technology, Harbin Medical University , No. 157 Baojian Road, Nangang District, Harbin 150086, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyu","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Medical Informatics, Daqing Campus, Harbin Medical University , No. 39 Xinyang Road, High Tech Zone, Daqing 163319, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuefeng","family":"Bai","sequence":"additional","affiliation":[{"name":"School of Medical Informatics, Daqing Campus, Harbin Medical University , No. 39 Xinyang Road, High Tech Zone, Daqing 163319, China"},{"name":"State Key Laboratory of Genetic Engineering, Human Phenome Institute and School of Life Sciences, Fudan University , No. 2005 Songhu Road, Yangpu District, Shanghai 200438, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuqi","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Cardiology, The Second Affiliated Hospital of Harbin Medical University , No. 246 Xuefu Road, Nangang District, Harbin 150086, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meiling","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Cardiology, The Second Affiliated Hospital of Harbin Medical University , No. 246 Xuefu Road, Nangang District, Harbin 150086, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Cardiology, The Second Affiliated Hospital of Harbin Medical University , No. 246 Xuefu Road, Nangang District, Harbin 150086, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yani","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Cardiology, The Second Affiliated Hospital of Harbin Medical University , No. 246 Xuefu Road, Nangang District, Harbin 150086, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaofang","family":"Ban","sequence":"additional","affiliation":[{"name":"Department of Cardiology, The Second Affiliated Hospital of Harbin Medical University , No. 246 Xuefu Road, Nangang District, Harbin 150086, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Xiong","sequence":"additional","affiliation":[{"name":"Department of Cardiology, The Second Affiliated Hospital of Harbin Medical University , No. 246 Xuefu Road, Nangang District, Harbin 150086, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chengyu","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Cardiology, The Second Affiliated Hospital of Harbin Medical University , No. 246 Xuefu Road, Nangang District, Harbin 150086, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Meng","sequence":"additional","affiliation":[{"name":"Department of Cardiology, The Second Affiliated Hospital of Harbin Medical University , No. 246 Xuefu Road, Nangang District, Harbin 150086, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuxin","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Cardiology, The Second Affiliated Hospital of Harbin Medical University , No. 246 Xuefu Road, Nangang District, Harbin 150086, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Cardiology, The Second Affiliated Hospital of Harbin Medical University , No. 246 Xuefu Road, Nangang District, Harbin 150086, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Cardiology, The Second Affiliated Hospital of Harbin Medical University , No. 246 Xuefu Road, Nangang District, Harbin 150086, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shan","family":"Zhong","sequence":"additional","affiliation":[{"name":"Department of Cardiology, The Second Affiliated Hospital of Harbin Medical University , No. 246 Xuefu Road, Nangang District, Harbin 150086, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinjian","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Cardiology, The Second Affiliated Hospital of Harbin Medical University , No. 246 Xuefu Road, Nangang District, Harbin 150086, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Cardiology, The Second Affiliated Hospital of Harbin Medical University , No. 246 Xuefu Road, Nangang District, Harbin 150086, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Shenzhen People\u2019s Hospital (The Second Clinical Medical College, Jinan University; The First Affiliated Hospital, Southern University of Science and Technology) , No. 1017 Dongmen North Road, Luohu District, Shenzhen 518000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1129-3147","authenticated-orcid":false,"given":"Yan","family":"Zheng","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Genetic Engineering, Human Phenome Institute and School of Life Sciences, Fudan University , No. 2005 Songhu Road, Yangpu District, Shanghai 200438, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2730-0033","authenticated-orcid":false,"given":"Jinwei","family":"Tian","sequence":"additional","affiliation":[{"name":"Department of Cardiology, The Second Affiliated Hospital of Harbin Medical University , No. 246 Xuefu Road, Nangang District, Harbin 150086, China"},{"name":"The Key Laboratory of Myocardial Ischemia, Harbin Medical University, Ministry of Education , No. 246 Xuefu Road, Nangang District, Harbin 150086, China"},{"name":"Key Laboratory of Emergency and Trauma of Ministry of Education, Hainan Medical University , No. 3 Xueyuan Road, Longhua District, Haikou 571199, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,10,6]]},"reference":[{"key":"2023101007424831700_R1","doi-asserted-by":"crossref","first-page":"11695","DOI":"10.18632\/oncotarget.2586","article-title":"Gastrokine 1 induces senescence and\u00a0apoptosis through regulating telomere length in\u00a0gastric cancer","volume":"5","author":"Yoon","year":"2014","journal-title":"Oncotarget"},{"key":"2023101007424831700_R2","doi-asserted-by":"crossref","first-page":"D825","DOI":"10.1093\/nar\/gkaa894","article-title":"Aging Atlas: a multi-omics database for\u00a0aging biology","volume":"49","author":"Liu","year":"2021","journal-title":"Nucleic Acids Res."},{"key":"2023101007424831700_R3","doi-asserted-by":"crossref","DOI":"10.1038\/cddis.2015.414","article-title":"CSGene: a literature-based database for\u00a0cell senescence genes and\u00a0its application to identify critical cell aging pathways and\u00a0associated diseases","volume":"7","author":"Zhao","year":"2016","journal-title":"Cell Death Dis."},{"key":"2023101007424831700_R4","doi-asserted-by":"crossref","first-page":"594","DOI":"10.1111\/acel.12585","article-title":"The DrugAge database of\u00a0aging-related drugs","volume":"16","author":"Barardo","year":"2017","journal-title":"Aging Cell"},{"key":"2023101007424831700_R5","doi-asserted-by":"crossref","first-page":"D1083","DOI":"10.1093\/nar\/gkx1042","article-title":"Human ageing genomic resources: new and\u00a0updated databases","volume":"46","author":"Tacutu","year":"2018","journal-title":"Nucleic Acids Res."},{"key":"2023101007424831700_R6","doi-asserted-by":"crossref","first-page":"2383","DOI":"10.1093\/emboj\/21.10.2383","article-title":"Human SIR2 deacetylates p53 and\u00a0antagonizes PML\/p53-induced cellular senescence","volume":"21","author":"Langley","year":"2002","journal-title":"EMBO J."},{"key":"2023101007424831700_R7","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.27041","article-title":"The Human Cell Atlas","volume":"6","author":"Regev","year":"2017","journal-title":"eLife"},{"key":"2023101007424831700_R8","doi-asserted-by":"crossref","DOI":"10.1093\/database\/bar046","article-title":"CELLPEDIA: a repository for\u00a0human cell information for\u00a0cell studies and\u00a0differentiation analyses","volume":"2011","author":"Hatano","year":"2011","journal-title":"Database"},{"key":"2023101007424831700_R9","doi-asserted-by":"crossref","first-page":"D869","DOI":"10.1093\/nar\/gkv1317","article-title":"GWASdb v2: an update database for\u00a0human genetic variants identified by genome-wide association studies","volume":"44","author":"Li","year":"2016","journal-title":"Nucleic Acids Res."},{"key":"2023101007424831700_R10","doi-asserted-by":"crossref","first-page":"D1001","DOI":"10.1093\/nar\/gkt1229","article-title":"The NHGRI GWAS Catalog, a curated resource of\u00a0SNP-trait associations","volume":"42","author":"Welter","year":"2014","journal-title":"Nucleic Acids Res."},{"key":"2023101007424831700_R11","doi-asserted-by":"crossref","first-page":"D971","DOI":"10.1093\/nar\/gkx861","article-title":"PancanQTL: systematic identification of\u00a0cis-eQTLs and\u00a0trans-eQTLs in\u00a033 cancer types","volume":"46","author":"Gong","year":"2018","journal-title":"Nucleic Acids Res."},{"key":"2023101007424831700_R12","doi-asserted-by":"crossref","first-page":"D930","DOI":"10.1093\/nar\/gkr917","article-title":"HaploReg: a resource for\u00a0exploring chromatin states, conservation, and\u00a0regulatory motif alterations within sets of\u00a0genetically linked variants","volume":"40","author":"Ward","year":"2012","journal-title":"Nucleic Acids Res."},{"key":"2023101007424831700_R13","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1089\/bio.2015.29031.hmm","article-title":"The Genotype-Tissue Expression (GTEx) project","volume":"13","author":"Carithers","year":"2015","journal-title":"Biopreserv Biobank"},{"key":"2023101007424831700_R14","doi-asserted-by":"crossref","first-page":"D545","DOI":"10.1093\/nar\/gkaa970","article-title":"KEGG: integrating viruses and\u00a0cellular organisms","volume":"49","author":"Kanehisa","year":"2021","journal-title":"Nucleic Acids Res."},{"key":"2023101007424831700_R15","doi-asserted-by":"crossref","first-page":"D687","DOI":"10.1093\/nar\/gkab1028","article-title":"The reactome pathway knowledgebase 2022","volume":"50","author":"Gillespie","year":"2022","journal-title":"Nucleic Acids Res."},{"key":"2023101007424831700_R16","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/gb-2010-11-1-r3","article-title":"NetPath: a public resource of\u00a0curated signal transduction pathways","volume":"11","author":"Kandasamy","year":"2010","journal-title":"Genome 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Res."},{"key":"2023101007424831700_R25","doi-asserted-by":"crossref","first-page":"1304","DOI":"10.1093\/gerona\/glu180","article-title":"MicroRNA-34a induces vascular smooth muscle cells senescence by SIRT1 downregulation and\u00a0promotes the expression of\u00a0age-associated pro-inflammatory secretory factors","volume":"70","author":"Badi","year":"2015","journal-title":"J. Gerontol. A Biol. Sci. Med. Sci."},{"key":"2023101007424831700_R26","doi-asserted-by":"crossref","first-page":"580","DOI":"10.1038\/ng.2653","article-title":"The Genotype-Tissue Expression (GTEx) project","volume":"45","author":"Lonsdale","year":"2013","journal-title":"Nat. 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