One comparatively unexplored path to clearing senescent cells from the aged body is to coerce portions of the immune system into working harder. In youth, the immune system is adept at removing senescent cells, and does so at a fast enough page to prevent accumulation. In old age, this process slows down. Here, researchers report on an in vitro demonstration of the potential for natural killer cells to clear senescent cells, marking their function as a potential target for the development of novel senolytic therapies capable of rejuvenation through the selective removal of senescent cells. Deciduous Therapeutics is a startup biotech company currently pursuing this path.
Previous experiments have shown that natural killer (NK) cells are partially responsible for the clearance of senescent cells from the human body. While some senescent cells have ways of avoiding detection and clearance, NK cells are attracted to certain parts of the senescence-associated secretory phenotype (SASP), which trigger them to kill the cells expressing it. Techniques are being developed to use this senolytic ability of NK cells as a potential therapy.
After taking NK cells out of whole blood, researchers sought to change the distribution of these cells. NK cells express different amounts of CD56 and CD16. NK cells that express high CD56 but low CD16 are immature and secrete interferon-γ; NK cells with low CD56 and high CD16 are responsible for cytotoxicity: the actual killing of other cells. The enrichment process, which involved activating the cells through the cytokine IL-2, substantially increased the percentages of both of these cell types.
These enriched cells were found to be very good at selectively eliminating senescent cells after 16 hours. In an experiment with one NK cell for every senescent cell, 15% of normal fibroblasts and 43% of senescent fibroblasts died. These numbers remained largely the same regardless of how senescence was induced, and endothelial cells yielded similar results to fibroblasts. Doubling or tripling the number of NK cells did kill more senescent cells; however, it also increased the number of normal cells being killed in the process. Therefore, instead of using more NK cells, the researchers increased the time in co-culture; while the number of normal fibroblasts dying remained low, only 10% of senescent cells survived after four days' exposure to fresh, enriched NK cells.