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A novel multi-tissue RNA diagnostic of healthy ageing relates to cognitive health status
XRGenomics Ltd, London, England.;Kings Coll London, Div Genet & Mol Med, Guys Hosp, London SE1 9RT, England..
XRGenomics Ltd, London, England.;Univ Stirling, Sch Hlth, Stirling FK9 4LA, Scotland..
Kings Coll London, Dept Old Age Psychiat, London SE1 9RT, England..
Karolinska Univ Hosp, Div Clin Physiol, Stockholm, Sweden..
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2015 (English)In: Genome Biology, ISSN 1465-6906, E-ISSN 1474-760X, Vol. 16, 185Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
2015. Vol. 16, 185
National Category
Geriatrics
Identifiers
URN: urn:nbn:se:uu:diva-263430DOI: 10.1186/s13059-015-0750-xISI: 000360683600001PubMedID: 26343147OAI: oai:DiVA.org:uu-263430DiVA: diva2:859567
Funder
EU, FP7, Seventh Framework ProgrammeKnut and Alice Wallenberg FoundationSwedish Research CouncilNIH (National Institute of Health)Swedish Society for Medical Research (SSMF)
Available from: 2015-10-07 Created: 2015-09-30 Last updated: 2017-12-01Bibliographically approved

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Cederholm, TommyLannfelt, Lars

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