The future: New tools to rejuvenate older organs?
Intriguing experimental work suggests senolytics, which selectively eliminate senescent cells, can rejuvenate older organs!
Recent impressive findings from a group of US, German and Japanese researchers(1) reveal that transplanting organs from old donors that had been treated with senolytics can restore their functional survival! Studies on old donor hearts, for example, treated with the senolytics Dasatinib plus Quercetin in a clinically-relevant model of immunosuppressed recipients, resulted in comparable survival of hearts from both old and young donor mice. Remarkably, 80% of hearts from treated old donors survived the 100-day observation period, while 80% of organs from old untreated donors survived only 37 days!
Although the research was primarily conducted on hearts and kidneys, their intriguing findings provide a rationale for application of the concept to other donor organs too, including the lung. Assuming these experimental findings can be translated to the clinical scenario, it seems reasonable to consider future treatment of lungs and other organs with senolytics added directly to the organ perfusate during warm ex-vivo organ perfusion.
Their work also suggests that some of the age effect is due to release of cell-free mitochondrial DNA during reperfusion, generating an inflammatory response. It can be speculated that minimizing ischemia-reperfusion injury, another role for EVLP, may also contribute to better tolerance of older donors.
XVIVO Insights PB-2021-02-04
