An intestinal microRNA modulates the homeostatic adaptation to chronic oxidative stress in C. elegans

Aging (Albany NY). 2016 Sep 12;8(9):1979-2005. doi: 10.18632/aging.101029.


Adaptation to an environmental or metabolic perturbation is a feature of the evolutionary process. Recent insights into microRNA function suggest that microRNAs serve as key players in a robust adaptive response against stress in animals through their capacity to fine-tune gene expression. However, it remains largely unclear how a microRNA-modulated downstream mechanism contributes to the process of homeostatic adaptation. Here we show that loss of an intestinally expressed microRNA gene, mir-60, in the nematode C. elegans promotes an adaptive response to chronic - a mild and long-term - oxidative stress exposure. The pathway involved appears to be unique since the canonical stress-responsive factors, such as DAF-16/FOXO, are dispensable for mir-60 loss to enhance oxidative stress resistance. Gene expression profiles revealed that genes encoding lysosomal proteases and those involved in xenobiotic metabolism and pathogen defense responses are up-regulated by the loss of mir-60. Detailed genetic studies and computational microRNA target prediction suggest that endocytosis components and a bZip transcription factor gene zip-10, which functions in innate immune response, are directly modulated by miR-60 in the intestine. Our findings suggest that the mir-60 loss facilitates adaptive response against chronic oxidative stress by ensuring the maintenance of cellular homeostasis.

Keywords: C. elegans; adaptive response; aging; microRNA; oxidative stress.

MeSH terms

  • Adaptation, Physiological / physiology*
  • Animals
  • Caenorhabditis elegans
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / metabolism*
  • Cation Transport Proteins / genetics
  • Cation Transport Proteins / metabolism
  • Gene Expression Profiling
  • Homeostasis / physiology*
  • Intestinal Mucosa / metabolism*
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Oxidative Stress / physiology*
  • Signal Transduction / physiology
  • Transcription, Genetic
  • Up-Regulation


  • Caenorhabditis elegans Proteins
  • Cation Transport Proteins
  • MicroRNAs