The role of PCKalpha and modulation of desmosomal adhesion in delayed wound healing in the elderly

皮肤上的伤口并不总是很快愈合的，随着时间的推移，可能会导致残疾、痛苦甚至死亡，以及巨额的医疗费用。随着高危年龄组的老年人越来越多，这个问题正在增加，但我们还不完全理解为什么老年人的愈合情况不佳。皮肤伤口通过一系列复杂的事件愈合，这些事件受到严格的调控，涉及几种细胞类型。我们的团队已经证明，女性激素雌激素对愈合有有益的影响，并对伤口中所有不同类型的细胞起作用。我们对年龄对上层皮肤(表皮)的影响和外层皮肤屏障的重建的了解特别差。我们实验室最近的研究，比较了老年人和年轻人的伤口愈合方式，发现上层皮肤中的细胞黏附(由称为桥粒的特殊结构赋予)是导致老年人愈合不良的关键过程。此外，我们已经证明，在皮肤受伤后，桥粒会发生特殊的变化。这些新的研究对于回答一些重要的问题至关重要，这些问题包括这些变化是如何调节的，以及对改善老年人延迟愈合的影响。我们的工作最初将使用培养的细胞和经过改造的表达桥粒蛋白的小鼠来了解生物学。这将指导对人体样本的实验，最终将导致开发新的治疗方法来加速老年人的愈合。

Wounds to the skin do not always heal quickly and over time can lead to disability, distress, or even death, and huge health care costs. This problem is increasing as we have more people in the elderly at-risk age-group, but we do not yet fully understand why older people have poor healing. Skin wounds heal through a complex series of events, which are carefully regulated and involve several cell types. Our group have shown that the female hormone estrogen has a beneficial effect on healing, and acts upon all of the different cell types in a wound. Our understanding of the effects of age on the upper skin layer (the epidermis) and reformation of the outer skin barrier is particularly poor. Recent studies from our laboratory, comparing how wounds from old and young subjects heal, have identified cell adhesion in this upper skin layer (conferred by specialised structures called desmosomes) as a key process that leads to poor healing in the elderly. Furthermore, we have shown that desmosomes undergo specific changes after the skin is wounded. These new studies are essential to answer a number of important questions including how these changes are regulated and the implications for improving delayed healing in the elderly. Our work will initially use cultured cells and mice modified to express desmosomal proteins to understand the biology. This will direct experiments on human samples that will ultimately lead to the development of new treatments to accelerate healing in the elderly.