Aging and biomarkers: Transcriptional levels evaluation of Osteopontin/miRNA-181a axis in hepatic tissue of rats in different age ranges.

ABSTRACT

Osteopontin (OPN), a novel hepatic damage marker, as well as several non-coding RNA seem to be associated with liver aging, a little studied and not yet defined process. The aim of the study was to evaluate the expression variations of OPN and miRNA-181a, the transcriptional profiling of long non coding (lnc) RNA GAS-5/miRNA-222 axis and lncRNA NEAT-1 in liver tissue of rats. In addition, to monitor the senescence process, the telomere shortening and TERT/TERC gene expression were also measured. Three groups of male Wistar rats were studied A (n = 6, young); B (n = 13, adult); C (n = 10, old). Total RNA, including miRNAs, was extracted from liver and analysed by Real-Time PCR. Ultrasound and biochemical evaluation were performed in all rats as well as the histological analysis. OPN mRNA resulted lower in C with respect to A and B while miRNA-181a expression was significantly increased as a function of age. An increasing of both NEAT-1 and miRNA-222 expression as a function of age in parallel with a decreasing of GAS-5 expression in young and old rats, but not in the adults, was observed. A positive correlation was detected between miRNA-181a and miRNA-222. The hepatic ultrasound analysis revealed areas of hyperechogenicity distributed as a function of age. A significant telomere shortening was measured as a function of age while the two subunits TERT and TERC expressions showed an opposite trend. This work could provide a valid starting point to better understand the physiopathological changes during aging, pinpointing in the OPN/miRNA-181a axis significant predictors of successful aging.