Identifying the impact of skin senescence through the lifecourse

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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.