Inflamma-miRs, Mito-miRs, and SA-miRs: Are They at the Crossroads of Inflammaging?

Context: Inflammaging is the latest theory of aging, which is the chronic, low-grade, and systematic inflammation developing the major risk factors for age-related diseases. Inflammaging is characterized by increasing the circulating pro-inflammatory factors and decreasing the circulatory anti-inflammatory factors. Recent findings propose that several classes of microRNAs are differentially expressed during inflammaging. Evidence Acquisition: Inflamma-miRs are a class of miRs capable of regulating the inflammatory status owing to their ability to modulate pro-inflammatory molecules. Since the role of miRNAs in aging is not restricted to inflammation, mito-miRs and SA-miRs are also involved in organismal aging. Considering the important role of mitochondria in aging, dysfunctional mitochondria in aged cells may induce an inflammatory response by producing ROS, as well as oxidized mtDNA and mito-miRNAs. Another important subset of miRNA that fuels inflammaging is senescence-associated miRNA (SA-miRs) that promotes senescence-associated secretory phenotype. Senescent cells have dysfunctional mitochondria, which can promote inflammaging through continuous immune system stimulation. Results: The evaluation of three classes of miRNAs involved in inflammaging shows that there are some miRs at the intersection of inflamma-miRs, SA-miRs, and mito-miRs, called SA-inflamma-mitomiRs subset, which contains miR-19b, miR-20a, miR-146a, and miR-181a. Conclusions: This overlap shows that this panel of miRNAs has mitochondrial targets whose modulation is implicated in senescence-associated secretory phenotype and the formation of SASP might be an important contributor to chronic inflammation.