miR-21 and miR-146a: The microRNAs of inflammaging and age-related diseases

The first paper on inflammaging published in 2001 paved the way for a unifying theory on how and why aging turns out to be the main risk factor for the development of the most common age-related diseases (ARDs). The most exciting challenge on this topic was explaining how systemic inflammation steeps up with age and why it shows different rates among individuals of the same chronological age. The epigenetic revolution in the past twenty years conveyed that the assessment of the individual genetic make-up is not enough to depict the trajectories of age-related inflammation. Accordingly, others and we have been focusing on the role of non-coding RNA, i.e. microRNAs (miRNAs), in inflammaging. The results obtained in the latest 10 years underpinned the key role of a miRNA subset that we have called inflammamiRs, owing to their ability to master (NF-kappa B)-driven inflammatory pathways. In this review, we will focus on two inflammamiRs, i.e. miR-21-5p and miR-146a-5p, which target a variety of molecules belonging to the NF-kappa B/NLRP3 pathways. The interplay between miR146a-5p and IL-6 in the context of aging and ARDs will also be highlighted. We will also provide the most relevant evidence suggesting that circulating inflammamiRs, along with IL-6, can measure the degree of inflammaging.

Automated summary

Inflammaging is a key concept in understanding how aging contributes to the development of age-related diseases, with a focus on the role of miRNAs in regulating inflammatory pathways. The assessment of individual genetic make-up alone is insufficient to depict the trajectories of age-related inflammation, and studies have shown that circulating inflammamiRs could be used to measure the degree of inflammaging.