A Role for microRNAs in the Regulation of Longevity due to Mitochondrial Impairment

Along with being the main source of ATP in the cell, mitochondria play crucial roles
in a variety of cellular functions. In the mitochondria ATP is produced by a chain of
complexes known as the mitochondrial electron transport chain (ETC), whose mild impairment leads to life extension in several model organisms such as C. elegans. Mild interference with the ETC is associated with transcriptional reprogramming that results in life extension.

microRNAs are conserved small non-coding RNAs that affect gene expression by downregulation of mRNA translation and stability. microRNAs have been implicated in many longevity pathways, but not in longevity induced by mild interference with the ETC.

In this study we show that the microRNA machinery is essential for the longevity induced by mild interference with the ETC. Deep sequencing transcriptome analysis demonstrated that the vast majority of the transcriptional changes in this pathway depend on the integrity of the microRNA processing machinery. Thus, identification of the related longevity-promoting microRNAs and their targets would help us understand the regulation of the pro-longevity transcriptional program induced by ETC impairment.

Given the conservation of microRNAs and the mitochondrial longevity pathway from C. elegans to mammals, this study may identify targets that may be relevant to human longevity as well.