CELLULAR SENESCENSE-CON

The consensus that cell senescence plays a role in age-related disease has prompted a number of potential clinical interventions, including attempts to reset cell senescence and attempts to remove senescent cells from aging tissues. The latter approach, senolytic therapy, has attracted considerable attention, but both theoretical considerations and published data suggest that the clinical benefits will be transient and that senolytic therapies will likely accelerate long-term degenerative disease. We review the overall field, its history, the theoretical aspects, and the available data. The long-term risks are underestimated and based on naïve assumptions, while the long-term benefits are not borne out by physiologic considerations or data. Senolytics are likely to accelerate tissue pathology, exacerbate clinical disease, and result in early morbidity and mortality.