P39 Lysosomal expansion and dysfunction: a feature of UVB-induced senescence in dermal fibroblasts

Abstract Introduction and aims Dermal fibroblasts play a critical role in regulating the dermal tissue layer, which is essential for providing the skin with mechanical strength. With age, the dermis atrophies and is affected by matrix regulation. Age-associated accumulation of senescence is also observed in the dermis, often as a consequence of stressors such as ultraviolet (UV)B-induced DNA damage. The pathogenicity of senescent cells is primarily linked to their deleterious secretory profile, this secretory profile requires high metabolic demands and persistent mammalian target of rapamycin complex 1 signalling at the lysosome. Therefore, expansion of the lysosomal compartment is crucial in supporting the senescent phenotype. Methods The research here characterizes the expansion and diminished health of lysosomes in an optimized UVB-induced senescence model in dermal human fibroblast. Specifically, flow cytometry and the use of fluorogenic substrates have been employed to demonstrate the diminished functionality of lysosomes in UVB-induced senescence. Results Biochemical analyses further identify enhanced lysosomal exocytosis in senescent cells, further exemplifying lysosomal dysfunction as part of the senescence programme. Conclusions It is hoped that collectively these data will emphasize the underappreciated role of lysosomal dysfunction in UVB-induced senescence, and postulate this dysfunction as a key player in the pathogenicity of senescence.