Figure 3.

Animal models of regeneration have provided evidence of the interplay between macrophages and senescent cells during tissue regeneration. The induction of cellular senescence leads to the initiation of the senescence-associated secretory phenotype (SASP) during salamander limb regeneration, zebrafish fin regeneration and post-partum uterus regeneration. In the absence of macrophages, senescent cells in the regenerating salamander limb are not cleared, which is a possible reason for impaired regeneration (dashed grey arrow) [48]. The removal of either senescent cells or macrophages during zebrafish regeneration has a deleterious effect on regeneration, hypothesized to be as a result of altering the tightly regulated balance of cell senescence (dashed grey arrows) [125]. The mammalian uterus undergoes extensive remodelling post-partum where senescent cells are normally cleared by macrophages. In the absence of macrophages, senescent cells accumulate in the uterus [126], presumably leading to dysregulated regeneration and function (dashed grey arrow). Created with Biorender.com.