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dc.contributor.authorSood, S
dc.contributor.authorGallagher, IJ
dc.contributor.authorLunnon, Katie
dc.contributor.authorRullman, E
dc.contributor.authorKeohane, A
dc.contributor.authorCrossland, H
dc.contributor.authorPhillips, BE
dc.contributor.authorCederholm, T
dc.contributor.authorJensen, T
dc.contributor.authorvan Loon, LJ
dc.contributor.authorLannfelt, L
dc.contributor.authorKraus, WE
dc.contributor.authorAtherton, PJ
dc.contributor.authorHoward, R
dc.contributor.authorGustafsson, T
dc.contributor.authorHodges, A
dc.contributor.authorTimmons, JA
dc.date.accessioned2016-02-10T14:29:27Z
dc.date.issued2015-09-07
dc.description.abstractBACKGROUND: Diagnostics of the human ageing process may help predict future healthcare needs or guide preventative measures for tackling diseases of older age. We take a transcriptomics approach to build the first reproducible multi-tissue RNA expression signature by gene-chip profiling tissue from sedentary normal subjects who reached 65 years of age in good health. RESULTS: One hundred and fifty probe-sets form an accurate classifier of young versus older muscle tissue and this healthy ageing RNA classifier performed consistently in independent cohorts of human muscle, skin and brain tissue (n = 594, AUC = 0.83-0.96) and thus represents a biomarker for biological age. Using the Uppsala Longitudinal Study of Adult Men birth-cohort (n = 108) we demonstrate that the RNA classifier is insensitive to confounding lifestyle biomarkers, while greater gene score at age 70 years is independently associated with better renal function at age 82 years and longevity. The gene score is 'up-regulated' in healthy human hippocampus with age, and when applied to blood RNA profiles from two large independent age-matched dementia case-control data sets (n = 717) the healthy controls have significantly greater gene scores than those with cognitive impairment. Alone, or when combined with our previously described prototype Alzheimer disease (AD) RNA 'disease signature', the healthy ageing RNA classifier is diagnostic for AD. CONCLUSIONS: We identify a novel and statistically robust multi-tissue RNA signature of human healthy ageing that can act as a diagnostic of future health, using only a peripheral blood sample. This RNA signature has great potential to assist research aimed at finding treatments for and/or management of AD and other ageing-related conditions.en_GB
dc.description.sponsorshipEuropean Commissionen_GB
dc.description.sponsorshipAlzheimer’s Research UKen_GB
dc.description.sponsorshipJohn and Lucille van Geest Foundationen_GB
dc.description.sponsorshipNational Institute for Health Research (NIHR)en_GB
dc.description.sponsorshipEuropean Medical Information Framework (EMIF)en_GB
dc.description.sponsorshipMedical Research Council (MRC)en_GB
dc.description.sponsorshipWallenberg Foundationen_GB
dc.description.sponsorshipKarolinska Instituteten_GB
dc.description.sponsorshipSwedish Medical Research Councilen_GB
dc.description.sponsorshipSwedish Society for Medical Research (SSMF)en_GB
dc.identifier.citationVol. 16, article 185en_GB
dc.identifier.doi10.1186/s13059-015-0750-x
dc.identifier.grantnumberFP6-2004-LIFESCIHEALTH-5en_GB
dc.identifier.grantnumber115372en_GB
dc.identifier.grantnumberFP7/2007-2013en_GB
dc.identifier.grantnumberG1100015/1en_GB
dc.identifier.grantnumberD0328602en_GB
dc.identifier.urihttp://hdl.handle.net/10871/19682
dc.language.isoenen_GB
dc.publisherBioMed Centralen_GB
dc.relation.urlhttp://www.ncbi.nlm.nih.gov/pubmed/26343147en_GB
dc.rights© Sood et al. Open Access. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.en_GB
dc.titleA novel multi-tissue RNA diagnostic of healthy ageing relates to cognitive health statusen_GB
dc.typeArticleen_GB
dc.date.available2016-02-10T14:29:27Z
exeter.place-of-publicationEngland
dc.identifier.journalGenome Biologyen_GB
dc.identifier.pmcidPMC4561473
dc.identifier.pmid6343147


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