Targeted Senolytic Strategies Based on the Senescent Surfaceome

The clearance of senescent cells has the potential to become a therapeutic strategy that could be used in many pathologies, ranging from pulmonary fibrosis and diabetes to ageing itself. The initial genetic experiments performed in mouse models are now being recapitulated using chemical compounds that preferentially kill senescent cells, known as senolytics. Senolytic drugs hold an immense clinical potential but their lack of specificity could lead to side effects that would limit their use, especially when treating otherwise healthy aged individuals. Thus, it would be convenient to develop more targeted approaches to the elimination of senescent cells. Here, we discuss the ongoing efforts to design targeted senolytics, with special focus on the utilization of the extracellular epitopes displayed by the senescent surfaceome, and we summarize the avenues of research that have shown the most promising results so far: nanotechnology, cellular therapies and antibody-based drug delivery.