Manuel has been working on cellular senescence for almost 30 years since his discovery of the master senescence gene p16. He combines work on senescence with cellular reprogramming. His group was the first to report that reprogramming can be achieved within tissues, and this is strongly promoted by tissue damage signals. Manuel's team is currently focused on the mechanisms of cellular rejuvenation by partial reversible reprogramming and its similarities with tissue repair. The overarching goal of his research is to find pharmacological and dietary interventions that mimic partial reversible reprogramming and trigger rejuvenation.