THU0019 Are micrornas a molecular clock? the newcastle thousand families cohort study
Authors: T.L. Jones, D.A. Young, M.S. Pearce, A. Skelton, F.N. Birrell
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> No single biomarker has been identified for monitoring ageing trajectory. To date, biological clocks are based on DNA methylation, telomere length, p16<sup>ink4a</sup> expression and microsatellite mutations<sup>1</sup>. Body ageing is a complex phenomenon, including a progressive, pro-inflammatory state, termed 'inflammaging'. MicroRNAs have been linked with cellular senescence and inflammaging. MicroRNAs are short, non-coding sequences of RNA regulating post-transcriptional gene expression with impressive stability and ubiquitous presence, making them ideal candidate biomarkers. Previous studies of circulating microRNAs in ageing were small-scale<sup>2</sup> or compared individuals of different ages, which is methodologically less robust<sup>3</sup>. MicroRNA biomarkers can bring greater understanding to ageing mechanisms, diagnosis/prognosis of age-related disease and even novel treatment targets. <h3>Objectives</h3> To quantify relationships between circulating microRNA expression and biological ageing and determine whether microRNAs may be a molecular clock. <h3>Methods</h3> This pilot work is a nested substudy within a prospective, longitudinal birth cohort from May/June 1947 (the Newcastle Thousand Families Study NTFS). Serum samples from 23 subjects taken at ages 50 and 62 years were extracted from the biobank. HTG EdgeSeq microRNA whole transcriptome assay was performed, measuring expression of 2083 human microRNA transcripts using an array followed by next generation sequencing. Global microRNA expression profiles were generated and analysed using this technology, profiling all known microRNAs from a small volume of serum (&lt;15 µL). NIHR funding has been secured for whole cohort analysis. <h3>Results</h3> Resulting data has shown very strong associations (up to p&lt;10–1<sup>2</sup>) for biological ageing, with 84 microRNAs meeting p-values&lt;0.05 (see heat map). Analysing the whole cohort will independently validate and extend the findings, in order to identify an ageing signature; the molecular clock. <h3>Conclusions</h3> This study suggests very strong changes in microRNAs in individuals between 50 and 62, suggesting microRNA signature is a molecular clock. These observations need to be confirmed and extended to validate serum microRNAs as biomarkers for ageing, for early detection of age-related disease and as tools to monitor ageing trajectory. <h3>References</h3> [1] Hatse S, et al. Circulating MicroRNAs as Easy-to-Measure Aging Biomarkers in Older Breast Cancer Patients: Correlation with Chronological Age but Not with Fitness/Frailty Status. PLoS ONE2014;9(10):e110644. [2] Zhang H, et al. Investigation of microRNA expression in human serum during the aging process. J Gerontol A Biol Sci Med Sci. 2015;70(1):1–2–9. [3] Ameling S, et al. Associations of circulating plasma microRNAs with age, body mass index and sex in a population-based study. BMC Med Genomics2015;8:61. <h3>Acknowledgements</h3> Whole cohort analysis: funding secured from NIHR Biomedical Research Centre for Ageing, Newcastle-upon Tyne, UK and benefits from an industry partnership with HTG Molecular, Inc, USA. <h3>Disclosure of Interest</h3> None declared