Senotherapeutics for healthy ageing

Excerpt

One current tactic to provide evidence that a compound has senolytic activity is the ‘hit-and-run’ approach, for example, the one-time treatment of mice with dasatinib and quercetin following hind-leg irradiation3. Here, a single administration of dasatinib plus quercetin yielded a therapeutic benefit that endured for months in terms of treadmill performance, consistent with a senolytic mechanism in which disease-causing cells are killed.

In general, if a short course of treatment yields a sustained reduction in senescence, it is likely acting in a senolytic manner. In contrast, if chronic treatment is needed to suppress senescence markers or prevent secondary senescence, this is more consistent with senomorphic activity.

However, more refined approaches are needed to rapidly demonstrate senolytic activity in vivo. Likely combinations of approaches may be necessary. For example, if a drug kills senescent endothelial cells, it could yield a health dividend, but it will be very difficult to document a reduction in the expression of senescence markers specifically in the endothelium without sophisticated reporter systems.