Age-dependent regulation of tumor-related microRNAs in the brain of the annual fish Nothobranchius furzeri

Mech Ageing Dev. 2012 May;133(5):226-33. doi: 10.1016/j.mad.2012.03.015. Epub 2012 Apr 6.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / genetics*
  • Animals
  • Brain / metabolism*
  • Down-Regulation
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Killifishes / metabolism*
  • Longevity / genetics
  • Male
  • MicroRNAs / biosynthesis*
  • MicroRNAs / genetics
  • Oncogene Protein p55(v-myc) / metabolism
  • Oncogenes*
  • Up-Regulation


  • MicroRNAs
  • Oncogene Protein p55(v-myc)