The Nutrigenomic Effect of Mela Rosa Marchigiana Callus Extract on Cellular Senescence: Insight From a Preliminary In Vitro Study

Mela Rosa Marchigiana (MRM) is an apple variety cultured in the center of Italy. Calluses derived from in vitro culture of MRM explants were used to obtain an ethanolic extract rich in pentacyclic triterpenic acids with putative anti-inflammatory and anti-aging effects. In this study, we investigated the transcriptomic and epigenetic effects of MRM callus extract (MRME) in an in vitro model of cellular senescence. Senescent HUVECs (sHUVECs) were treated with MRME. Transcriptomic analysis was performed to compare young HUVECs (yHUVECs) with sHUVECs and to evaluate the MRME's effect on sHUVECs. Results show that senescence induces major changes in the transcriptome of HUVECs. MRME downregulates TNF-α signaling genes in sHUVECs restoring the expression to that observed in yHUVECs. Genome-wide DNA methylation analysis performed using the Oxford-Nanopore sequencing platform did not reveal significant changes in DNA methylation levels induced by MRME. Our preliminary results provide additional evidence suggesting that MRME exerts anti-inflammatory and anti-aging effects, which may be mediated by the modulation of the expression of inflammaging genes via mechanisms independent of DNA methylation. These findings highlight MRME as a promising candidate for further in vivo studies aimed at exploring its clinical translational potential in counteracting inflammaging.