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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\u2010associated fragments (tRFs), and piwi\u2010interacting RNAs (piRNAs) was measured in serum from 21 healthy and 21 sarcopenic Hertfordshire Sarcopenia Study extension women matched for age (mean 78.9\u2009years) and HOMA2\u2010IR. Associations with age, sarcopenia and HOMA2\u2010IR 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\u2009&lt;\u20090.05) 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 (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u2009.05) with 12 tRNAs, 3 tRFs, and 6 piRNAs, with target genes linked to cell proliferation and differentiation such as Notch Receptor 1 (\n                    <jats:italic>NOTCH1<\/jats:italic>\n                    ), DISC1 scaffold protein (\n                    <jats:italic>DISC1<\/jats:italic>\n                    ), and GLI family zinc finger\u20102 (\n                    <jats:italic>GLI2<\/jats:italic>\n                    ). HOMA2\u2010IR was nominally associated (p&lt;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\u2010associated pathologies and provide novel targets for therapeutic intervention.\n                  <\/jats:p>","DOI":"10.1096\/fj.202301089rr","type":"journal-article","created":{"date-parts":[[2024,1,31]],"date-time":"2024-01-31T09:05:37Z","timestamp":1706691937000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["The serum small non\u2010coding\n                    <scp>RNA<\/scp>\n                    (\n                    <scp>SncRNA<\/scp>\n                    ) landscape as a molecular biomarker of age associated muscle dysregulation and insulin resistance in older adults"],"prefix":"10.1096","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7117-8151","authenticated-orcid":false,"given":"Mark A.","family":"Burton","sequence":"first","affiliation":[{"name":"Human Development and Health Academic Unit, Faculty of 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