title: Age-dependent regulation of tumor-related microRNAs in the brain of the annual fish Nothobranchius furzeri.
abstract: MicroRNAs are regulators of gene expression. We used miRNA-seq by the Illumina platform to quantify and compare the temporal miRNA expression profiles in the brain of a short-lived (GRZ) and a longer-lived strain (MZM) of the annual fish Nothobranchius furzeri. We used fuzzy-c-means clustering to group miRNAs with similar profiles. In MZM, we found tumor suppressors with known negative interactions with MYC and/or positive interactions with TP53 among up-regulated miRNAs (e.g. miR-23a, miR-26a/b, miR-29a/b and miR-101a) in aged animals. Conversely, we found oncogenes which are MYC targets among down-regulated miRNAs (miR-7a, members of miR cluster 17∼92). These latter were previously shown to be regulated in human replicative aging. In addition, three regulated miRNAs (miR-181c, miR-29a and miR-338) are known to be age-regulated and to globally contribute to regulation of their targets in the human brain. Therefore, there appears to be a degree of evolutionarily conservation in age-dependent miRNA expression between humans and N. furzeri. GRZ showed specific regulation of some miRNAs, notably a marked up-regulation of miR-124, a miRNA important for neuronal differentiation. The two strains differ in their miRNA expression profiles already at sexual maturity. Short lifespan in GRZ could therefore be--at least partially--due to dysregulated miRNA expression.
authors.affiliation: Biology of Ageing, Leibniz Institute for Age Research, Fritz-Lipmann Institute, Jena, Germany.
authors.forename: Mario
authors.initials: M
authors.lastname: Baumgart
authors.forename: Marco
authors.initials: M
authors.lastname: Groth
authors.forename: Steffen
authors.initials: S
authors.lastname: Priebe
authors.forename: Jessika
authors.initials: J
authors.lastname: Appelt
authors.forename: Reinhard
authors.initials: R
authors.lastname: Guthke
authors.forename: Matthias
authors.initials: M
authors.lastname: Platzer
authors.forename: Alessandro
authors.initials: A
authors.lastname: Cellerino
mesh_terms: D000375:Aging / Q000235:genetics*; D000818:Animals; D001921:Brain / Q000378:metabolism*; D015536:Down-Regulation; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007695:Killifishes / Q000378:metabolism*; D008136:Longevity / Q000235:genetics; D008297:Male; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics; D016274:Oncogene Protein p55(v-myc) / Q000378:metabolism; D009857:Oncogenes; D015854:Up-Regulation
chemical_list: D035683:MicroRNAs; D016274:Oncogene Protein p55(v-myc)