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

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. 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.

Automated summary

In this Comment, the authors highlight the non-apoptotic roles of BCL-2 proteins in regulating cellular senescence and caution against the use of BCL-2 inhibitors as senolytics. While BCL-2 and related proteins are known for their role in apoptosis regulation, recent findings suggest their involvement in cellular senescence through non-apoptotic mechanisms.