Identifying the impact of skin senescence through the lifecourse

细胞衰老是一个公认的驱动组织和有机体老化。虽然衰老作为一种肿瘤抑制机制是有益的，但衰老细胞在许多组织（包括皮肤）中与年龄相关的积累会导致组织功能、完整性和再生能力的下降。衰老被定义为细胞周期的不可逆退出，是对潜在的转化细胞应激（如癌基因激活和DNA损伤）的反应。尽管不能分裂，但生长和代谢途径在衰老过程中仍然活跃，导致氧化应激增加和一系列极具炎症性的分泌因子的产生，包括细胞因子、生长因子和细胞外基质成分。这个博士项目将扩展我们之前的出版物，并在体外和体内研究不同皮肤相关细胞类型的衰老代谢途径，以确定针对这些途径是否具有抗衰老潜力并改善皮肤健康和功能。最终，我们的目标是开发和验证一种局部抗衰老化合物，我们假设这种化合物将改善皮肤衰老的许多方面，包括减少炎症、减少氧化应激和改善ECM网络。

Cellular senescence is a well-established driver of tissue and organismal ageing. While senescence is beneficial as a tumour suppressor mechanism, age-related accumulation of senescent cells in many tissues, including skin leads to a decline in tissue function, integrity and regeneration capacity. Senescence is defined as an irreversible exit from the cell cycle and occurs in response to potentially transformative cell stress such as oncogene activation and DNA damage. Despite not being able to divide, growth and metabolic pathways are still active in senescence, leading to the characteristic hallmarks such as increased oxidative stress and production of an extremely inflammatory set of secretory factors, including cytokines, growth factors and extracellular matrix components. This PhD project will expand on our previous publications and investigate metabolic pathways in senescence of different skin-associated cell types in vitro and in vivo to determine whether targeting these pathways has senolytic potential and improves skin health and function. Ultimately, the aim is to develop and validate a topical senolytic compound which we hypothesise will improve many aspects of skin ageing including reduced inflammation, reduced oxidative stress and improved ECM networks.