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

Genome Biology
Sanjana SoodJames A Timmons

Abstract

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. 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, o...Continue Reading

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Datasets Mentioned

BETA
GSE47969
GSE11882
GSE60862
GSE63060
GSE63061
GSE59880
GSE9419
GSE28422
GSE47881

Methods Mentioned

BETA
gene-chip
biopsy
PCR
in vitro transcription
chip
X-ray
biopsies

Software Mentioned

R
ToppGene
Ingenuity Pathway Analysis ( IPA )
IPA
LUMI
Bioconductor
survival
R stats package
limma
R package ROCR

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