During skin aging, fibroblasts undergo senescence and profoundly accumulate in the skin. Senescent fibroblasts secrete a battery of soluble factors, termed as Senescence Associated Secretory Phenotype (SASP). Because of their soluble nature, SASP factors spread senescence to neighboring cells in the skin and most likely to other organs. This is in contrast to the transient SASP release during embryogenesis and wound healing which is beneficial for tissue remodeling. During tissue remodeling, the senescent cells are successfully removed by cells of the innate immune system such as Natural Killer (NK) cells. We are therefore interested to understand whether senescent fibroblasts are resistant to the removal by NK cells, or NK cells are themselves compromised to remove senescent fibroblasts from aging skin. We have observed that the both primary NK cells and NK cell lines preferentially kill senescent fibroblasts to non-senescent fibroblasts. Although there is no change in the absolute number of NK cells in peripheral blood and skin between young (~25 years) and old (~70 years) healthy human individuals, primary NK cells from old individuals (~70 years) are profoundly less efficient in killing senescent human dermal fibroblasts compared to the killing ability of primary NK cell from young individuals (~25 years). Furthermore, release of perforin and granzyme B, the effector molecules which induces pores formation and killing of the target cells, is significantly reduced in NK cells from old individual (~70 years) compared to NK cells from young individuals. These data indicates that possibly aging of NK cells may contribute to reduced removal of senescent cells. These data advance our understanding of mechanisms underlying senescent cell accumulation in skin, and may even be exploited for future senolytic therapies.

ESDR345 - Impaired Senescent Fibroblast Clearance by NK Cells During Skin Aging

The scientific meeting of the European Society for Dermatological Research (ESDR) is held yearly, usually in September. With an international attendance of more than 1000 skin scientists from around the globe, the four-day event includes short oral presentations from peer-reviewed abstracts, keynote lectures from international experts, sponsored symposia, satellite programs, educational events as well as an important focus on posters, networking and building collaborations amongst scientists. For more information about this year’s meeting visit our website.