Figure 7. Proposed model showing differential effects of mitoR-34a, -146a and -181a on young and senescent HUVECs. Acute expression of mitomiRs in yHUVECs negatively modulates Bcl-2 expression, induces mPTP opening, caspase-1 and caspase-3 activation and autophagy. These biochemical and functional changes can be responsible of the pro-apoptotic effect exerted by mitomiRs. Conversely, although the progressive expression of miR-34a, miR-146a and miR-181a in sHUVECs during replicative senescence exerts biochemical changes similar to yHUVECs, they are more resistant to apoptosis, maybe due to the over-expression of other anti-apoptotic proteins (SCAPSs, i.e. Survivin and Bcl-xL) thus producing high amount of ROS and accumulating AVs. Overall, dysfunctional cells accumulate during aging, exerting detrimental effects on nearby cells and promoting inflammation. Senolytic drugs, by reducing over-expressed SCAPs, can ultimately kill dysfunctional sHUVECs.