title: MicroRNAs miR-203-3p, miR-664-3p and miR-708-5p are associated with median strain lifespan in mice.
abstract: MicroRNAs (miRNAs) are small non-coding RNA species that have been shown to have roles in multiple processes that occur in higher eukaryotes. They act by binding to specific sequences in the 3' untranslated region of their target genes and causing the transcripts to be degraded by the RNA-induced silencing complex (RISC). MicroRNAs have previously been reported to demonstrate altered expression in several aging phenotypes such as cellular senescence and age itself. Here, we have measured the expression levels of 521 small regulatory microRNAs (miRNAs) in spleen tissue from young and old animals of 6 mouse strains with different median strain lifespans by quantitative real-time PCR. Expression levels of 3 microRNAs were robustly associated with strain lifespan, after correction for multiple statistical testing (miR-203-3p [β-coefficient = -0.6447, p = 4.8 × 10-11], miR-664-3p [β-coefficient = 0.5552, p = 5.1 × 10-8] and miR-708-5p [β-coefficient = 0.4986, p = 1.6 × 10-6]). Pathway analysis of binding sites for these three microRNAs revealed enrichment of target genes involved in key aging and longevity pathways including mTOR, FOXO and MAPK, most of which also demonstrated associations with longevity. Our results suggests that miR-203-3p, miR-664-3p and miR-708-5p may be implicated in pathways determining lifespan in mammals.
authors.affiliation: RNA-mediated mechanisms of Disease, Institute of Biomedical and Clinical Sciences, University of Exeter Medical School, University of Exeter, Devon, UK.
authors.forename: Benjamin P
authors.initials: BP
authors.lastname: Lee
authors.affiliation: RNA-mediated mechanisms of Disease, Institute of Biomedical and Clinical Sciences, University of Exeter Medical School, University of Exeter, Devon, UK.
authors.forename: Ivana
authors.initials: I
authors.lastname: Burić
authors.affiliation: RNA-mediated mechanisms of Disease, Institute of Biomedical and Clinical Sciences, University of Exeter Medical School, University of Exeter, Devon, UK.
authors.forename: Anupriya
authors.initials: A
authors.lastname: George-Pandeth
authors.affiliation: The Jackson Laboratory Nathan Shock Center of Excellence in the Basic Biology of Aging, Bar Harbor, Maine, USA.
authors.forename: Kevin
authors.initials: K
authors.lastname: Flurkey
authors.affiliation: The Jackson Laboratory Nathan Shock Center of Excellence in the Basic Biology of Aging, Bar Harbor, Maine, USA.
authors.forename: David E
authors.initials: DE
authors.lastname: Harrison
authors.affiliation: The Jackson Laboratory Nathan Shock Center of Excellence in the Basic Biology of Aging, Bar Harbor, Maine, USA.
authors.forename: Rong
authors.initials: R
authors.lastname: Yuan
authors.affiliation: The Jackson Laboratory Nathan Shock Center of Excellence in the Basic Biology of Aging, Bar Harbor, Maine, USA.
authors.forename: Luanne L
authors.initials: LL
authors.lastname: Peters
authors.affiliation: UConn Centre on Aging, University of Connecticut Health Centre, Farmington, Connecticut, USA.
authors.forename: George A
authors.initials: GA
authors.lastname: Kuchel
authors.affiliation: UConn Centre on Aging, University of Connecticut Health Centre, Farmington, Connecticut, USA.|Epidemiology and Public Health, Institute of Biomedical and Clinical Sciences, University of Exeter Medical School, University of Exeter, Devon, UK.
authors.forename: David
authors.initials: D
authors.lastname: Melzer
authors.affiliation: RNA-mediated mechanisms of Disease, Institute of Biomedical and Clinical Sciences, University of Exeter Medical School, University of Exeter, Devon, UK.
authors.forename: Lorna W
authors.initials: LW
authors.lastname: Harries
mesh_terms: D000818:Animals; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D008136:Longevity / Q000235:genetics*; D008815:Mice, Inbred Strains; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics
chemical_list: C575934:MIRN203 microRNA, mouse; C000629097:MIRN664 microRNA, mouse; D035683:MicroRNAs; D012333:RNA, Messenger; C000626520:mirn708 microRNA, mouse