DNA damage response (DDR) and senescence: shuttled inflamma-miRNAs on the stage of inflamm-aging

// Fabiola Olivieri 1,2 , Maria Cristina Albertini 3 , Monia Orciani 1 , Artan Ceka 1 , Monica Cricca 4 , Antonio Domenico Procopio 1,2 and Massimiliano Bonafè 4 1 Department of Clinical and Molecular Sciences (DISCLIMO), Università Politecnica delle Marche, Ancona, Italy 2 Center of Clinical Pathology and Innovative Therapy, Italian National Research Center on Aging, INRCA-IRCCS, Ancona, Italy 3 Department of Biomolecular Sciences, Biochemistry and Molecular Biology, Università degli Studi di Urbino “Carlo Bo”, Urbino, Italy 4 Department of Experimental, Diagnostic and Specialty Medicine, DIMES, University of Bologna, Bologna, Italy Correspondence to: Fabiola Olivieri, email: // Keywords : microRNA, senescence(definition)-associated secretory phenotype, senescence, inflamm-aging, Gerotarget Received : June 18, 2015 Accepted : September 17, 2015 Published : September 29, 2015 Abstract A major issue in aging research is how cellular phenomena affect aging at the systemic level. Emerging evidence suggests that DNA damage response (DDR) signaling is a key mechanism linking DNA damage accumulation, cell senescence, and organism aging. DDR activation in senescent cells promotes acquisition of a proinflammatory secretory phenotype (SASP), which in turn elicits DDR and SASP activation in neighboring cells, thereby creating a proinflammatory environment extending at the local and eventually the systemic level. DDR activation is triggered by genomic lesions as well as emerging bacterial and viral metagenomes. Therefore, the buildup of cells with an activated DDR probably fuels inflamm-aging and predisposes to the development of the major age-related diseases (ARDs). Micro (mi)-RNAs - non-coding RNAs involved in gene expression modulation - are released locally and systemically by a variety of shuttles (exosomes, lipoproteins, proteins) that likely affect the efficiency of their biological effects. Here we suggest that some miRNAs, previously found to be associated with inflammation and senescence - miR-146, miR-155, and miR-21 - play a central role in the interplay among DDR, cell senescence and inflamm-aging. The identification of the functions of shuttled senescence-associated miRNAs is expected to shed light on the aging process and on how to delay ARD development.