BCL-2 proteins in senescence: beyond a simple target for senolysis?

BCL-2 and related proteins are major regulators of apoptosis that have emerged as promising targets for the elimination senescent cells (or ‘senolysis’) to improve age-related diseases and promote healthy ageing. However, seminal observations and recent findings shed light on non-apoptotic roles of BCL-2 proteins in the regulation of cellular senescence. In this Comment, the authors draw attention to non-apoptotic roles of BCL-2 proteins in the regulation of cellular senescence and voice the need for caution in using BCL-2 inhibitors as senolytics.