Please use this identifier to cite or link to this item: http://hdl.handle.net/2381/44356
Full metadata record
DC FieldValueLanguage
dc.contributor.authorRowland, J-
dc.contributor.authorAkbarov, A-
dc.contributor.authorEales, J-
dc.contributor.authorXu, X-
dc.contributor.authorDormer, JP-
dc.contributor.authorGuo, H-
dc.contributor.authorDenniff, M-
dc.contributor.authorJiang, X-
dc.contributor.authorRanjzad, P-
dc.contributor.authorNazgiewicz, A-
dc.contributor.authorPrestes, PR-
dc.contributor.authorAntczak, A-
dc.contributor.authorSzulinska, M-
dc.contributor.authorWise, IA-
dc.contributor.authorZukowska-Szczechowska, E-
dc.contributor.authorBogdanski, P-
dc.contributor.authorWoolf, AS-
dc.contributor.authorSamani, NJ-
dc.contributor.authorCharchar, FJ-
dc.contributor.authorTomaszewski, M-
dc.date.accessioned2019-06-11T13:20:57Z-
dc.date.available2019-06-11T13:20:57Z-
dc.date.issued2019-02-20-
dc.identifier.citationKidney International, 2019, 95 (3), pp. 624-635en
dc.identifier.urihttps://www.sciencedirect.com/science/article/pii/S0085253818308378?via%3Dihuben
dc.identifier.urihttp://hdl.handle.net/2381/44356-
dc.descriptionSupplementary material is linked to the online version of the paper at www.kidney-international.org.en
dc.description.abstractNephrons scar and involute during aging, increasing the risk of chronic kidney disease. Little is known, however, about genetic mechanisms of kidney aging. We sought to define the signatures of age on the renal transcriptome using 563 human kidneys. The initial discovery analysis of 260 kidney transcriptomes from the TRANScriptome of renaL humAn TissuE Study (TRANSLATE) and the Cancer Genome Atlas identified 37 age-associated genes. For 19 of those genes, the association with age was replicated in 303 kidney transcriptomes from the Nephroseq resource. Surveying 42 nonrenal tissues from the Genotype-Tissue Expression project revealed that, for approximately a fifth of the replicated genes, the association with age was kidney-specific. Seventy-three percent of the replicated genes were associated with functional or histological parameters of age-related decline in kidney health, including glomerular filtration rate, glomerulosclerosis, interstitial fibrosis, tubular atrophy, and arterial narrowing. Common genetic variants in four of the age-related genes, namely LYG1, PPP1R3C, LTF and TSPYL5, correlated with the trajectory of age-related changes in their renal expression. Integrative analysis of genomic, epigenomic, and transcriptomic information revealed that the observed age-related decline in renal TSPYL5 expression was determined both genetically and epigenetically. Thus, this study revealed robust molecular signatures of the aging kidney and new regulatory mechanisms of age-related change in the kidney transcriptome.en
dc.description.sponsorshipSupported by PG/17/35/33001 from the British Heart Foundation and RP_017_20180302 from Kidney Research UK (MT), RP_021_20170302 from Kidney Research UK (AW and PR), and APP1123472 from the National Health and Medical Research Council Australia (FJC).en
dc.language.isoenen
dc.publisherElsevier for International Society of Nephrologyen
dc.relation.urihttps://www.ncbi.nlm.nih.gov/pubmed/30784661-
dc.rightsCopyright © the authors, 2019. This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.en
dc.subjectagingen
dc.subjectepigenomeen
dc.subjectgeneticsen
dc.subjectkidneyen
dc.subjecttranscriptomeen
dc.titleUncovering genetic mechanisms of kidney aging through transcriptomics, genomics, and epigenomics.en
dc.typeJournal Articleen
dc.identifier.doi10.1016/j.kint.2018.10.029-
dc.identifier.eissn1523-1755-
dc.identifier.piiS0085-2538(18)30837-8-
dc.description.statusPeer-revieweden
dc.description.versionPublisher Versionen
dc.type.subtypeJournal Article-
pubs.organisational-group/Organisationen
pubs.organisational-group/Organisation/COLLEGE OF LIFE SCIENCESen
pubs.organisational-group/Organisation/COLLEGE OF LIFE SCIENCES/School of Medicineen
pubs.organisational-group/Organisation/COLLEGE OF LIFE SCIENCES/School of Medicine/Department of Cardiovascular Sciencesen
pubs.organisational-group/Organisation/COLLEGE OF LIFE SCIENCES/Themesen
pubs.organisational-group/Organisation/COLLEGE OF LIFE SCIENCES/Themes/Cardiovascularen
pubs.organisational-group/Organisation/COLLEGE OF LIFE SCIENCES/Themes/Genome Scienceen
dc.dateaccepted2018-10-18-
Appears in Collections:Published Articles, Dept. of Cardiovascular Sciences

Files in This Item:
File Description SizeFormat 
Uncovering genetic mechanisms of kidney aging through transcriptomics, genomics, and epigenomics.pdfPublished (publisher PDF)2.39 MBAdobe PDFView/Open


Items in LRA are protected by copyright, with all rights reserved, unless otherwise indicated.