“Ageing and many diseases are partly driven by the accumulation of damaged cells that no longer divide. It emerges that these senescent cells can be eradicated in mice using a drug that interferes with the activity of the protein FOXO4.
If cells incur too much damage, they undergo either a self-elimination process known as apoptosis or a self-disabling process called senescence. Senescent cells can be long-lived, and so accumulate in aged and damaged organs1. The elimination of senescent cells is known2,3,4,5,6 to increase healthy lifespan and reduce the severity of age-related diseases in mice. Writing in Cell, Baar et al.7 expand our understanding of this phenomenon. They report that senescent cells depend on the transcription factor forkhead box protein O4 (FOXO4) for their survival, and show in mouse models that both age-associated defects and tissue dysfunction caused by chemotherapy can be reversed by pharmacologically perturbing the function of this protein.
Senescent cells forcibly block their own capacity to proliferate while programming themselves to secrete signalling molecules — a phenomenon known as the senescence-associated secretory phenotype (SASP). It has been proposed8,9 that the normal function of the SASP is to restore tissue function in two ways: first, by stimulating less-damaged neighbouring cells to engage in tissue repair; and second, by attracting inflammatory cells to eliminate senescent cells and turn off SASP-mediated signals. However, this restorative process may fail when the extent, duration or frequency of damage exceeds repair capacity, or when reparative and inflammatory cells become unresponsive to the effects of the SASP. The end result is an aberrant accumulation of senescent cells that, contrary to their initial purpose, aggravate tissue dysfunction.” Serrano, M. Tools to eliminate senescent cells. Nature545, 294–295 (2017) doi:10.1038/nature22493
