Gene expression in human mesenchymal stem cell aging cultures: modulation by short peptides.

Effects of the short peptides Ala-Glu-Asp (AED), Lys-Glu-Asp (KED) and Lys-Glu (KE) on the expression of IGF1, FOXO1, TERT, TNKS2, and NFκB genes were studied in human embryo bone marrow mesenchymal stem cells (line FetMSCs) variously aged in "passages" or "stationary" cultures. Both cell aging models were similar in gene expression. The main difference was in the TERT gene expression level, which showed an eightfold increase at the "stationary" aging. IGF1 gene expression levels were very similar in both cell culture aging models, being enhanced by 3.5-5.6 fold upon the addition of the peptides. The FOXO1 gene was expressed twice more actively in the "stationary" than in the "passages" aging model. KED peptide inhibited FOXO1 gene expression by 1.6-2.3 fold. KE peptide increased FOXO1 gene expression by about two-fold in the "stationary" aging model but did not affect it in the "passage" aging model. The most striking difference in the peptide effect on cell aging between "passages" and "stationary" aging models was in the KED effects on TNKS2 gene expression; this expression was inhibited by KED in the "passages" model, while stimulation was observed in the "stationary" model. AED, KED, and KE stimulated expression of the NFκB gene in both models. Thus, the peptides studied at nanomolar concentrations modulate the expression of some genes known to be involved in cell aging.