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

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

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The Laboratory of Ageing, Centenary Institute, Camperdown, NSW 2050, Australia.
Sydney Medical School, The University of Sydney, Camperdown, NSW 2050, Australia.
Department of Biomedical Data Science, Geisel School of Medicine, Dartmouth College, Lebanon, NH 03756, USA.
Department of Molecular and Systems Biology, Geisel School of Medicine, Dartmouth College, Hanover, NH 03755, USA.


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.


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

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