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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.
Issue Date: 2015
Publisher: BioMed Central © Sood et al.
Citation: SOOD, S. ... et al, 2015. A novel multi-tissue RNA diagnostic of healthy ageing relates to cognitive health status. Genome Biology, 16 (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.
Description: This is an Open Access Article. It is published by BioMed Central under the Creative Commons Attribution 4.0 International Licence (CC BY). Full details of this licence are available at: http://creativecommons.org/licenses/by/4.0/
Sponsor: Parts of this work were supported by InnoMed, (Innovative Medicines in Europe) an Integrated Project funded by the European Union of the Sixth Framework program priority FP6-2004-LIFESCIHEALTH-5, Alzheimer’s Research UK, The John and Lucille van Geest Foundation, the National Institute of Health Research Biomedical Research Centre for Mental Health at the South London and Maudsley NHS Foundation Trust and [Institute of Psychiatry] Kings College London, Psychiatry Research Trust, Institute of Psychiatry and the Rosetrees Trust. AH receives support from the Innovative Medicines Initiative Joint Undertaking under EMIF grant agreement number 115372, resources of which are composed of financial contribution from the European Union’s Seventh Framework Programme (FP7/2007-2013) and EFPIA companies in kind contribution. The clinical validation studies were supported by a grant on ageing to JT from the Medical Research Council, UK (G1100015/1). Aspects of this study were also supported by the Wallenberg Foundation (TG), Karolinska Institutet (JT), Swedish Medical Research Council Grant D0328602 (TG) and an Affymetrix Translational Medicine Grant (JT). ER is partly supported by a grant from Swedish Society for Medical Research (SSMF). BEK (STRRIDE Study) was supported by the NIH.
Version: Published
DOI: 10.1186/s13059-015-0750-x
URI: https://dspace.lboro.ac.uk/2134/24805
Publisher Link: http://dx.doi.org/10.1186/s13059-015-0750-x
ISSN: 1474-760X
Appears in Collections:Published Articles (Sport, Exercise and Health Sciences)

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