Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Research Highlight
  • Published:

Ageing

MicroRNA tunes ageing pathway in flies

Nature Reviews Genetics volume 13, pages 222–223 (2012)Cite this article

Subjects

Following the observation that a mutation in an miRNA-processing gene leads to a shortened lifespan and late-onset brain neurodegeneration in Drosophila melanogaster, the authors set out to identify fly miRNAs that have age-modulated expression patterns in the adult brain. The expression of one such miRNA, miR-34, was very low during early development, but it increased with age. Null miR-34 mutants were normal as young adults but showed a striking decline in viability and locomotion, as well as morphological signs of neural deterioration at later time points, suggesting that miR-34 affects lifespan as well as adult brain integrity. These phenotypes are consistent with the finding that the brains of miR-34 mutants, but not wild-type flies, show transcriptional profiles that are associated with accelerated brain ageing. Experimentally increasing miR-34 levels gives opposite ageing phenotypes from loss-of-function mutations: these flies are protected from neurodegeneration and have an extended median lifespan.

miR-34 is predicted to target binding sites in the 3′ untranslated region (UTR) of the Ecdysone-induced protein 74EF (Eip74EF) mRNA, which encodes a transcription factor in the steroid hormone signalling pathway. Expression of one Eip74EF isoform, Eip74EFA, increases in late adulthood when miR-34 is absent; the increased miR-34 expression that is observed in normal adults could therefore serve to silence Eip74EFA expression during this period. The causal link between miR-34 function, Eip74EFA levels and ageing phenotypes was established by, among other methods, showing that Eip74EFA protein expression is elevated in animals in which Eip74EFA lacks miR-34-binding sites, leading to neurodegeneration phenotypes and poor survival.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

References

ORIGINAL RESEARCH PAPER

  1. Liu, N. et al. The microRNA miR-34 modulates ageing and neurodegeneration in Drosophila. Nature 15 Feb 2012 (doi:10.1038/nature10810)

FURTHER READING

  1. Lessing, D & Bonini, N. M. Maintaining the brain: insight into human neurodegeneration from Drosophila melanogaster mutants. Nature Rev. Genet. 10, 359–370 (2009)

    Article  CAS  Google Scholar 

Download references

Authors
  1. Tanita Casci
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Casci, T. MicroRNA tunes ageing pathway in flies. Nat Rev Genet 13, 222–223 (2012). https://doi.org/10.1038/nrg3205

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrg3205

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing