RNA surveillance-an emerging role for RNA regulatory networks in aging

In this review, we describe recent advances in the field of RNA regulatory biology and relate these advances to aging science. We introduce a new term, RNA surveillance, an RNA regulatory process that is conserved in metazoans, and describe how RNA surveillance represents molecular cross-talk between two emerging RNA regulatory systems-RNA interference and RNA editing. We discuss how RNA surveillance mechanisms influence mRNA and microRNA expression and activity during lifespan. Additionally, we summarize recent data from our own laboratory linking the RNA editor, ADAR, with exceptional longevity in humans and lifespan in Caenorhabditis elegans. We present data showing that transcriptional knockdown of RNA interference restores lifespan losses in the context of RNA editing defects, further suggesting that interaction between these two systems influences lifespan. Finally, we discuss the implications of RNA surveillance for sarcopenia and muscle maintenance, as frailty is a universal feature of aging. We end with a discussion of RNA surveillance as a robust regulatory system that can change in response to environmental stressors and represents a novel axis in aging science.