July 31st, 2026
Senescent cells accumulate with age in tissues throughout the body. These cells cease replication and secrete a potent mix of pro-growth, pro-inflammatory signaling that is disruptive to tissue structure and function when maintained over the long term. Cells become senescent throughout life in response to various circumstances, but in youth are efficiently destroyed by the immune system. With old age, the immune system falters in this task for reasons that are still being explored in detail. While the increased damage and disarray found in aged cells and tissues likely accelerates the pace at which cells become senescent, present evidence suggests that immune dysfunction in the matter of senescent cell clearance is the dominant factor in the increased presence of lingering senescent cells in later life.
Various approaches to selectively removing senescent cells from aged tissues have been demonstrated in animal studies, such as the first generation of senolytic drugs (including the combination of dasatinib and quercetin) that sabotage mechanisms that senescent cells use to resist programmed cell death. A number of the biotech companies founded to develop senolytic drugs are focused instead on immunotherapies, ways to adjust the behavior of the immune system so that it can better target senescent cells for destruction. Today's scientific paper reports a novel basis for anti-senescence immunotherapy, based on removing an impediment to the ability of macrophages to destroy senescent neutrophils. Beyond the novel senolytic approach, the work is interesting for demonstrating that senescent neutrophils in and of themselves make up a sizable fraction of the entire problem of cellular senescence, at least in the liver and heart.
