Deep sequencing of poly(A)-selected RNAs from whole nematode C. elegans during aging

MicroRNAs (miRNAs) have been implicated in gene regulation in many complex processes, including aging. Moreover, expression levels of many miRNAs are altered during aging, though we know little about the mechanisms that regulate this process. To address these issues, we investigated the network of regulatory factors that interact with miRNAs during aging. We found miR-71, a known promoter of normal lifespan, to be an especially important regulator of alg-1/Argonaute. Here we show that increased ALG-1 expression in aging mir-71 loss-of-function mutants was associated with an increased global miRNA abundance and deregulation of mRNA expression. Further, variability in gene expression and lifespan are diminished in mir-71 mutants. Thus, miR-71 appears to promote normal lifespan by directly repressing the expression of alg-1 and indirectly regulating miRNA expression levels and noise. Our findings demonstrate the broad impacts of miRNAs on gene regulation during aging.