Please use this identifier to cite or link to this item: http://hdl.handle.net/1893/22552
Appears in Collections:Faculty of Health Sciences and Sport Journal Articles
Peer Review Status: Refereed
Title: A novel multi-tissue RNA diagnostic of healthy ageing relates to cognitive health status
Authors: Sood, Sanjana
Gallagher, Iain J
Lunnon, Katie
Rullman, Eric
Keohane, Aoife
Crossland, Hannah
Phillips, Bethan E
Cederholm, Tommy
Jensen, Thomas
van, Loon Luc J C
Lannfelt, Lars
Kraus, William E
Atherton, Philip J
Howard, Robert
Gustafsson, Thomas
Hodges, Angela
Timmons, James A
Contact Email: i.j.gallagher@stir.ac.uk
Issue Date: Sep-2015
Publisher: BioMed Central
Citation: Sood S, Gallagher IJ, Lunnon K, Rullman E, Keohane A, Crossland H, Phillips BE, Cederholm T, Jensen T, van Loon LJC, Lannfelt L, Kraus WE, Atherton PJ, Howard R, Gustafsson T, Hodges A & Timmons JA (2015) A novel multi-tissue RNA diagnostic of healthy ageing relates to cognitive health status, Genome Biology, 16 (1), Art. No.: 185.
Abstract: Background: 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.
Type: Journal Article
URI: http://hdl.handle.net/1893/22552
DOI Link: http://dx.doi.org/10.1186/s13059-015-0750-x
Rights: © 2015 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.
Affiliation: King's College London
Sport
King's College London
Karolinska University Hospital
King's College London
King's College London
Derby Teaching Hospitals NHS Foundation Trust
Uppsala University
Medical Prognosis Institute A/S
University of Maastricht
Uppsala University
Duke University
University of Nottingham
King's College London
Karolinska University Hospital
King's College London
King's College London

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