Comparison of senescence-associated miRNAs in primary skin and lung fibroblasts

Alice C. Holly, Sushma Grellscheid, Pieter van de Walle, David Dolan, Luke C. Pilling, Darren J. Daniels, Thomas von Zglinicki, Luigi Ferrucci, David Melzer, Lorna W. Harries

Research output: Contribution to journalArticlepeer-review

Abstract

MicroRNAs are non-coding RNAs with roles in many cellular processes. Tissue-specific miRNA profiles associated with senescence have been described for several cell and tissue types. We aimed to characterise miRNAs involved in core, rather than tissue-specific, senescence pathways by assessment of common miRNA expression differences in two different cell types, with follow-up of predicted targets in human peripheral blood. MicroRNAs were profiled in early and late passage primary lung and skin fibroblasts to identify commonly-deregulated miRNAs. Expression changes of their bioinformatically-predicted mRNA targets were then assessed in both cell types and in human peripheral blood from elderly participants in the InCHIANTI study. 57/178 and 26/492 microRNAs were altered in late passage skin and lung cells respectively. Three miRNAs (miR-92a, miR-15b and miR-125a-3p) were altered in both tissues. 14 mRNA targets of the common miRNAs were expressed in lung and skin fibroblasts, of which two demonstrated up-regulation in late passage skin and lung cells (LYST; p = 0.02 [skin] and 0.02 [lung] INMT; p = 0.03 [skin] and 0.04 [lung]). ZMPSTE24 and LHFPL2 demonstrated altered expression in late passage skin cells only (p = 0.01 and 0.05 respectively). LHFPL2 was also positively correlated with age in peripheral blood (p value = 6.6 × 10−5). We find that the majority of senescence-associated miRNAs demonstrate tissue-specific effects. However, miRNAs showing common effects across tissue types may represent those associated with core, rather than tissue-specific senescence processes.

Original languageEnglish (US)
Pages (from-to)423-434
Number of pages12
JournalBiogerontology
Volume16
Issue number4
DOIs
StatePublished - Feb 21 2015
Externally publishedYes

Keywords

  • Cellular senescence
  • Gene expression
  • microRNA
  • Tissue specificity

ASJC Scopus subject areas

  • Geriatrics and Gerontology
  • Gerontology
  • Aging

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