Senolytic compounds are those capable of selectively destroying senescent cells. They are useful because the buildup of senescent cells over time is one of the root causes of aging. A number of mechanisms have been discovered by which senescent cells can be provoked into self-destruction, such as bcl-2 inhibition or interference in FOXO4-p53 interactions. These examples are fairly well understood. Other mechanisms are known but less well understood; they require more work in order to proceed on the production of improved senolytic compounds.
In some cases, however, the primary mechanism of action of a compound found to be senolytic through experimental screening isn’t yet known. The open access paper noted here is an example of how to move forward in this situation: the researchers report on their efforts to characterize the mechanism underlying the ability of piperlongumine to selectively destroy senescent cells. This line of work has been ongoing for a few years now; it takes time. Given sufficiently knowledge of the mechanism, however, it is usually possible to find or develop more effective candidate drugs in this family. Piperlongumine isn’t perfect, and can be improved upon.
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