942 Inefficient senescent fibroblast clearance in aging skin: The contribution of impaired natural killer cells

Cellular senescence, a state of permanent cell cycle arrest, is one the hallmarks tissue aging and age-related disorders. Stromal cells like fibroblasts, present in connective tissues play pivotal role organ homeostasis aging. We previously showed that senescent fibroblasts profoundly accumulated skin during Under some transient conditions, can be successfully removed by innate immune system, such as Natural Killer (NK) cells. here wanted to understand whether were resistant removal NK or alternatively, themselves inefficient remove fibroblasts. Using newly developed mediated killing assay, we line, primary human mouse preferentially killed Primary from old donor (∼70 years) mice (∼700 days) less efficient opposed those young (∼23 (∼100 days), respectively. Of note, there no changes number between individuals. Furthermore, at synapse cells, release granzyme B (GrB) was markedly reduced. Also, content perforin GrB significantly declined. Interestingly, recognition conjugation towards which are crucial for target lysis impaired. In conclusion, these findings suggest reduced ability combined outcome impaired production perforin. This cytotoxicity likely contributes accumulation other organs. These hold promise advance our knowledge on mechanisms underlying may exploited develop novel strategies against