Mayo Clinic Researchers Identify Three New Agents (Senolytics) That May Delay Onset of Aging

Mayo Clinic researchers have identified three new agents to add to the emerging repertoire of drugs that are intended to delay the onset of aging by targeting senescent cells, i.e., cells that contribute to frailty and other age-related conditions. A recent study of human cell cultures shows that the drugs—the flavone fisetin and two BCL-XL inhibitors (A1331852 and A1155463)--cleared senescent cells in vitro. Findings were published online on March 8, 2017 in Aging. The open-access article is titled “New Agents That Target Senescent Cells: The Flavone, Fisetin, and The BCL-XL Inhibitors, A1331852 and A1155463.” "Senescent cells accumulate with age and at sites of multiple chronic conditions, such as in fat tissue in diabetes, the lungs in chronic pulmonary diseases, the aorta in vascular disease, or the joints in osteoarthritis," says James Kirkland, M.D., Ph.D., Director of the Mayo’s Robert and Arlene Kogod Center on Aging. "At Mayo Clinic, we discovered the first senolytic drugs - agents that selectively eliminate senescent cells while leaving normal cells unaffected. These senolytic agents alleviated a range of age- and disease-related problems in mice. We used the hypothesis-driven approach that we used to discover the first senolytic drugs, two published in early 2015 and another later in 2015, to discover these three new senolytic drugs." Mayo Clinic researchers, working in collaboration with the University Medical Center Groningen and The Scripps Research Institute, induced senescence in human cell cultures by radiating human primary preadipocytes, human umbilical vein endothelial cell cultures, and IMR90 cell cultures. Then, using an ATPLite and a crystal violet assay, researchers measured cell viability and demonstrated that fisetin and BCL-XL inhibitors A1331852 and A1155463 cleared senescent cells in vitro.
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