Clinical Implications of Cellular Senescence on Wound Healing

Cellular senescence, a process where cells reach maximum proliferative capacity ceasing division without cell death, is involved in numerous processes, including organismal aging, tissue repair, and wound healing. Here, we review mechanisms underlying cellular senescence and discuss the role of different forms of senescence in physiologic cutaneous wound healing and in the pathology of non-healing wounds. In terms of wound healing, studies have shown that the cellular senescence exhibits a paradoxical effects where on one hand it promotes activity and differentiation of fibroblasts necessary during early stages of wound closure, while excess and persistent fibroblast senescence past the early stages of healing are commonly observed in chronic wounds. The complexity of the physiologic roles of cellular senescence are highly evident in the case of cutaneous wound healing, where senescent phenotypes display contradictory effects that are dependent on the timing, relative abundance and type of senescent cells required for optimal wound closure.