Centre for Atherothrombosis and Metabolic Disease, Hull York Medical School, The University of Hull, Hull, UK.
Exp Dermatol. 2021 Jan;30(1):68-73. doi: 10.1111/exd.14082. Epub 2020 Feb 21.
Arguably, the two most important causes of pathological healing in the skin are diabetes and ageing. While these factors have historically been considered independent modifiers of the healing process, recent studies suggest that they may be mechanistically linked. The primary contributor to diabetic pathology is hyperglycaemia, which accelerates the production of advanced glycation end products, a characteristic of ageing tissue. Indeed, advanced age also leads to mild hyperglycaemia. Here, we discuss emerging literature that reveals a hitherto unappreciated link between cellular senescence, diabetes and wound repair. Senescent cells cause widespread destruction of normal tissue architecture in ageing and have been shown to be increased in chronic wounds. However, the role of senescence remains controversial, with several studies reporting beneficial effects for transiently induced senescence in wound healing. We recently highlighted a direct role for senescence in diabetic healing pathology, mediated by the senescence receptor, CXCR2. These findings suggest that targeting local tissue senescence may provide a therapeutic strategy applicable to a broad range of chronic wound types.
可以说，皮肤病理性愈合的两个最重要原因是糖尿病和衰老。虽然这些因素在历史上被认为是愈合过程的独立调节剂，但最近的研究表明它们可能在机制上是相关的。糖尿病病理的主要贡献者是高血糖症，它加速了晚期糖基化终产物的产生，这是衰老组织的特征。事实上，高龄也会导致轻度高血糖症。在这里，我们讨论了新出现的文献，揭示了细胞衰老、糖尿病和伤口修复之间以前未被认识到的联系。衰老细胞导致衰老时正常组织结构的广泛破坏，并且已经在慢性伤口中增加。然而，衰老的作用仍然存在争议，一些研究报告称在伤口愈合中短暂诱导的衰老具有有益的影响。我们最近强调了衰老在糖尿病愈合病理中的直接作用，这是由衰老受体 CXCR2 介导的。这些发现表明，靶向局部组织衰老可能为广泛的慢性伤口类型提供一种治疗策略。
