Small Noncoding RNAs in Senescence and Aging

Abstract

Small noncoding RNAs (sncRNAs) of length shorter than 400 nucleotides mediate fundamental cellular functions in animals and plants. Some sncRNAs are complexed with proteins that direct them to nucleic acids with sequence complementarity, where they may cleave or otherwise alter the target thereby controlling gene expression, chromatin remodeling, and genome stability. Though microRNAs are the most characterized species, next generation sequencing technology has allowed the discovery of new types of sncRNAs that are generated by processing of known sncRNAs into smaller but functional RNA molecules. The recent discovery of stable sncRNAs in the extracellular space suggests that they may serve as signaling molecules that can enter target cells and regulate cellular functions. Organismal aging has been linked to cellular senescence and both involve extensive changes in gene expression. Calorie restriction (CR), a reduced caloric intake without malnutrition, protects against senescence and ameliorates the age-related dysfunctions. Since sncRNAs regulate gene expression and control genome stability, it is conceivable that they may contribute to the biological and functional changes that accompany the development of cellular senescence and the progression of organismal aging. Furthermore sncRNAs may very well mediate the beneficial effects of CR on senescence and aging. In this chapter, I will give an overview on the involvement of intracellular and extracellular microRNAs and sncRNAs derived from tRNA and YRNA in the regulation of cellular senescence and organismal aging and their potential role in mediating the beneficial actions of CR.