Metanalysis and characterization of new age-related miRNAs in nematodes C. elegans

Abstract

Aging and the consequent increase in the prevalence of chronic diseases are serious public health issues. These problems have been attracting the attention of governmental agencies and research centers with the aim to propose strategies to promote healthy aging. Among the molecular pathways described as important to control the rate of aging in different species, there is the microRNA (miRNA) pathway. Our previous data show that the levels of Dicer, a key enzyme for miRNA production, reduce with aging. Caloric restriction, an intervention that extends lifespan and increases stress resistance, also prevents this age-related decline of Dicer in the adipose tissue of mice and in the nematode Caenorhabditis elegans. Furthermore, overexpression of Dicer in the C. elegans intestine increases worm lifespan through the miRNA pathway. However, due to the high quantity of miRNAs and the diversity of its functions, data-processing tools become important to highlight those miRNAs with relevant roles in aging. Based on databases available in the literature and using bioinformatics tools, we performed a metanalysis to identify miRNAs differentially expressed in interventions that regulate lifespan in C. elegans. We found the families of mir-35-41 and mir-58 as candidates for new miRNAs that regulate aging. In general, the miRNAs of these families were upregulated in beneficial interventions, like caloric restriction, and downregulated in deleterious interventions, like oxidative stress. The biological functions of the mir-35-41 family, like the role in RNA interference (RNAi), are better described in literature than that of the mir-58 family. However, none of these families were reported as age-related until our analysis. Therefore, we intend to characterize the function of these miRNAs in normal aging and in interventions that increase lifespan. Additionally, we will evaluate the role of the miRNAs in C. elegans stress response. Due to their evolutionary conservation, this strategy could characterize new potential targets for aging regulation in more complex organisms and validate a computational approach to identify miRNAs that may regulate life expectancy. (AU)