Piperlongumine is a candidate senolytic agent, demonstrated to selectively destroy senescent cells in cell culture. Its ability to destroy senescent cells in vivo has not yet been confirmed, however, which would normally make it worthy of only academic interest. A sizable fraction of potential therapies fail to make the leap from cell culture to animal study. That said, unlike any of the senolytic candidates so far proven in animal studies, piperlongumine is a natural product, an extract of the long pepper. If it is usefully senolytic in mammals, then the regulatory path to widespread availability is much shorter and much less expensive than is the case for small molecule drugs.

Given this, there is considerable interest among patient advocates in the senolytic ability of piperlongumine in vivo. All it needs is an animal study with suitable accompanying measurements, and then it will be a matter of unleashing the supplement industry to work with regulators, mass manufacture, package, and distribute, giving them something worthwhile to do for a change. Unfortunately, while interesting, this study is not the study that we are still waiting for. The authors show that piperlongumine can achieve exactly the sort of results one would expect of a senolytic for cognitive decline in mice, mention senescent cells in passing, but do not assess whether or not the observed benefits resulted from clearance of senescent cells. This is frustrating, to say the least. The results here should be compared with the effects of the dasatinib and quercetin combination on neurodegeneration in a mouse model of Alzheimer's disease. It adds to the plausibility of piperlongumine as a useful senolytic, but plausibility is not proof.

Link: https://doi.org/10.3892/ijmm.2018.3782