Senolytic

A senolytic (from the words "senescence" and "lytic" - destroying) is among the class of small molecules under basic research to determine if they can selectively induce death of senescent cells. In basic research, senescence is a potential tumor suppressive mechanism and possible factor that accelerates the aging process. The goal of those working to develop senolytic agents is to delay, prevent, alleviate, or reverse age-related diseases.

Multiple possible senolytic agents are under investigation. Certain anti-cancer agents may in low doses decelerate aging and age-related diseases. Targeting cancer prevention pathways with anti-cancer agents may confer longevity effects by offering protection from metabolic pathologies during aging, independently of effects on cancer.

, also known as ABT-263, was originally studied as an anti-cancer drug. It is under basic research as a possible inhibitor of the anti-apoptotic proteins BCL-2, BCL-w, and BCL-xL. Navitoclax may have senolytic properties against some cell types (e.g., human umbilical vein epithelial cells (HUVECs), IMR90 human lung fibroblasts and murine embryonic fibroblasts (MEFs), but not all (e.g., human primary preadipocytes). In laboratory studies, oral administration of Navitoclax to either sublethally irradiated or normally aged mice reduced senescent cells, including bone marrow hematopoietic stem cells and muscle stem cells. It has toxic side effects, including thrombocytopenia and lymphopenia.

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