Affiliation:
1. Human Development and Health Academic Unit, Faculty of Medicine University of Southampton Southampton UK
2. NIHR Southampton Biomedical Research Centre University of Southampton and University Hospital Southampton NHS Foundation Trust Southampton UK
3. MRC Lifecourse Epidemiology Centre University of Southampton Southampton UK
4. Victoria University of Wellington Wellington New Zealand
5. Academic Geriatric Medicine, Faculty of Medicine University of Southampton Southampton UK
6. Biological Sciences University of Southampton Southampton UK
Abstract
AbstractSmall noncoding RNAs (sncRNAs) are implicated in age‐associated pathologies, including sarcopenia and insulin resistance (IR). As potential circulating biomarkers, most studies have focussed on microRNAs (miRNAs), one class of sncRNA. This study characterized the wider circulating sncRNA transcriptome of older individuals and associations with sarcopenia and IR. sncRNA expression including miRNAs, transfer RNAs (tRNAs), tRNA‐associated fragments (tRFs), and piwi‐interacting RNAs (piRNAs) was measured in serum from 21 healthy and 21 sarcopenic Hertfordshire Sarcopenia Study extension women matched for age (mean 78.9 years) and HOMA2‐IR. Associations with age, sarcopenia and HOMA2‐IR were examined and predicted gene targets and biological pathways characterized. Of the total sncRNA among healthy controls, piRNAs were most abundant (85.3%), followed by tRNAs (4.1%), miRNAs (2.7%), and tRFs (0.5%). Age was associated (FDR < 0.05) with 2 miRNAs, 58 tRNAs, and 14 tRFs, with chromatin organization, WNT signaling, and response to stress enriched among gene targets. Sarcopenia was nominally associated (p < .05) with 12 tRNAs, 3 tRFs, and 6 piRNAs, with target genes linked to cell proliferation and differentiation such as Notch Receptor 1 (NOTCH1), DISC1 scaffold protein (DISC1), and GLI family zinc finger‐2 (GLI2). HOMA2‐IR was nominally associated (p<0.05) with 6 miRNAs, 9 tRNAs, 1 tRF, and 19 piRNAs, linked with lysine degradation, circadian rhythm, and fatty acid biosynthesis pathways. These findings identify changes in circulating sncRNA expression in human serum associated with chronological age, sarcopenia, and IR. These may have clinical utility as circulating biomarkers of ageing and age‐associated pathologies and provide novel targets for therapeutic intervention.
Funder
Arthritis Research UK
Royal Osteoporosis Society
International Osteoporosis Foundation
National Institute for Health Research Southampton Biomedical Research Centre
University of Oxford
Biotechnology and Biological Sciences Research Council
Subject
Genetics,Molecular Biology,Biochemistry,Biotechnology