tRNA-Derived Fragments in Age-Related Diseases: A Systematic Review

Aging is a progressive weakening of numerous functions of organisms resulting in diminished abilities to safeguard against environmental damage and augment physiological harmony. It is not a disease in itself; however, it is a main cause of debilitating and life-threatening chronic aging-related diseases (ARDs). tRNA-derived fragments (tDRs) are stable forms of tRNAs of 14-35 nt in length that function as regulatory small-RNA molecules. Here we aimed to perform a systematic review of original articles on the involvement of tDRs in the etiology of ARDs: their identification and characterization. The systematic review was conducted according to the Cochrane Handbook guidelines and the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement. Based on the eligibility criteria defined for the study, 21 original articles were included in this systematic review, covering 11 ARDs. The preferred research method used to study tDRs was high-throughput sequencing combined with RT-qPCR, and as a result, a number of tDRs were implicated in ARDs. Importantly, an in-depth analysis of the articles allowed us to identify several shortcomings: (i) the tDRs nomenclature varies between studies and articles, making it often difficult to precisely identify molecules differentiating in a given disease; (ii) the chosen tDRs have all been studied for a miRNA-like mechanism of action; however, tDRs also function in RNAi-independent ways, which need to be studied as well; (iii) to precisely identify tDRs, the sequencing techniques that overcome the issues of modifications harbored by tRNAs must be used.