title: Comparison of senescence-associated miRNAs in primary skin and lung fibroblasts.
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.
authors.affiliation: Institute of Biomedical and Clinical Sciences, University of Exeter Medical School, University of Exeter, Barrack Road, Exeter, Devon, EX1 2LU, UK.
authors.forename: Alice C
authors.initials: AC
authors.lastname: Holly
authors.forename: Sushma
authors.initials: S
authors.lastname: Grellscheid
authors.forename: Pieter
authors.initials: P
authors.lastname: van de Walle
authors.forename: David
authors.initials: D
authors.lastname: Dolan
authors.forename: Luke C
authors.initials: LC
authors.lastname: Pilling
authors.forename: Darren J
authors.initials: DJ
authors.lastname: Daniels
authors.forename: Thomas
authors.initials: T
authors.lastname: von Zglinicki
authors.forename: Luigi
authors.initials: L
authors.lastname: Ferrucci
authors.forename: David
authors.initials: D
authors.lastname: Melzer
authors.forename: Lorna W
authors.initials: LW
authors.lastname: Harries
mesh_terms: D000367:Age Factors; D000375:Aging / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D049109:Cell Proliferation; D016922:Cellular Senescence / Q000235:genetics; D019295:Computational Biology; D005347:Fibroblasts / Q000378:metabolism*; D020869:Gene Expression Profiling / Q000379:methods; D005786:Gene Expression Regulation; D006801:Humans; D008168:Lung / Q000166:cytology / Q000378:metabolism*; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D012867:Skin / Q000166:cytology / Q000378:metabolism*; D013997:Time Factors
chemical_list: D035683:MicroRNAs