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  • Sood, SanjanaXRGenomics Ltd, London, England.;Kings Coll London, Div Genet & Mol Med, Guys Hosp, London SE1 9RT, England. (författare)

A novel multi-tissue RNA diagnostic of healthy ageing relates to cognitive health status

  • Artikel/kapitelEngelska2015

Förlag, utgivningsår, omfång ...

  • 2015-09-07
  • Springer Science and Business Media LLC,2015
  • electronicrdacarrier

Nummerbeteckningar

  • LIBRIS-ID:oai:DiVA.org:uu-263430
  • https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-263430URI
  • https://doi.org/10.1186/s13059-015-0750-xDOI
  • http://kipublications.ki.se/Default.aspx?queryparsed=id:131921700URI

Kompletterande språkuppgifter

  • Språk:engelska
  • Sammanfattning på:engelska

Ingår i deldatabas

Klassifikation

  • Ämneskategori:ref swepub-contenttype
  • Ämneskategori:art swepub-publicationtype

Anmärkningar

  • 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.

Ämnesord och genrebeteckningar

Biuppslag (personer, institutioner, konferenser, titlar ...)

  • Gallagher, Iain J.XRGenomics Ltd, London, England.;Univ Stirling, Sch Hlth, Stirling FK9 4LA, Scotland. (författare)
  • Lunnon, KatieKings Coll London, Dept Old Age Psychiat, London SE1 9RT, England. (författare)
  • Rullman, EricKarolinska Institutet,Karolinska Univ Hosp, Div Clin Physiol, Stockholm, Sweden. (författare)
  • Keohane, AoifeKings Coll London, Dept Old Age Psychiat, London SE1 9RT, England. (författare)
  • Crossland, HannahKings Coll London, Div Genet & Mol Med, Guys Hosp, London SE1 9RT, England.;Derby Royal Hosp, Sch Med, Derby, England. (författare)
  • Phillips, Bethan E.Derby Royal Hosp, Sch Med, Derby, England. (författare)
  • Cederholm, TommyKarolinska Institutet,Uppsala universitet,Klinisk nutrition och metabolism(Swepub:uu)tomce419 (författare)
  • Jensen, ThomasMed Prognosis Inst AS, Horsholm, Denmark. (författare)
  • van Loon, Luc J. C.Maastricht Univ, NUTRIM, Maastricht, Netherlands. (författare)
  • Lannfelt, LarsUppsala universitet,Geriatrik(Swepub:uu)lalan021 (författare)
  • Kraus, William E.Duke Univ, Sch Med, Duke Mol Physiol Inst, Durham, NC USA. (författare)
  • Atherton, Philip J.Derby Royal Hosp, Sch Med, Derby, England. (författare)
  • Howard, RobertKings Coll London, Dept Old Age Psychiat, London SE1 9RT, England. (författare)
  • Gustafsson, ThomasKarolinska Institutet,Karolinska Univ Hosp, Div Clin Physiol, Stockholm, Sweden. (författare)
  • Hodges, AngelaKings Coll London, Dept Old Age Psychiat, London SE1 9RT, England. (författare)
  • Timmons, James A.XRGenomics Ltd, London, England.;Kings Coll London, Div Genet & Mol Med, Guys Hosp, London SE1 9RT, England. (författare)
  • 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. (creator_code:org_t)

Sammanhörande titlar

  • Ingår i:Genome Biology: Springer Science and Business Media LLC161465-69061474-760X

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