Rejuvenate before the transfer

Despite the limited number of organs available to patients on transplant waiting lists, organs from old deceased donors are often not used. Their application would help to reduce the gap between supply and demand and reduce the waiting time for the operation.

Organs from older donors often cause an excessive immune response and increase the risk of adverse outcomes and transplant rejection in patients. But as the world's population ages, the organs of elderly deceased donors represent an untapped and ever-growing resource for patients in need. Researchers from Brigham Women's Hospital have focused efforts to breathe new life into old organs using senolytics that affect old cells and destroy them. Using clinical and experimental studies, the group has shown that senolytic drugs rejuvenate old organs, which can lead to better results and an expansion of the number of organs suitable for transplantation.

With age, aging cells accumulate in the organs. These cells no longer divide and avoid the body's usual means of destroying unnecessary cells. Aging cells secrete extracellular mitochondrial DNA (mtDNA), which also accumulates in old organs. Recent studies have shown that this mtDNA growth is associated with organ rejection after transplantation.

In their article in the journal Nature Communications, Stefan Tullius and his colleagues identified aging cells as a key source of mtDNA and presented evidence that the accumulation of mtDNA causes an immune response leading to organ failure and rejection. Senolytic drugs force aging cells to return to the cell cycle, allowing the body to remove them. Therefore, the researchers studied whether senolytics could be used to improve transplant outcomes. In experiments on mice, they treated organ donors with a combination of the senolytic drugs dasatinib and quercetin. The drugs reduced the number of aging cells, reduced mtDNA levels and reduced inflammation. It is likely that the survival rate of old organs treated with senolytics was comparable to the survival rate of organs obtained from young donors.

Since the authors conducted their therapeutic experiments on a mouse model, further research is needed to assess whether senolytic drugs can have the same effect on human organs from old donors and remove aging cells as effectively, as well as whether they can treat organs after sampling. The authors have already started human studies and determined that older donors have elevated mtDNA levels.

Senolytics have not yet been tested on human organs, but the group is already ready for clinical research, it is planned to use a perfusion device to deliver drugs to donor organs and measure whether there is a change in the number of aging cells. The results of the study will serve as a basis for the treatment of donors, organs intended for transplantation, and/or recipients with senolytic drugs to optimize the use of organs from elderly donors. The goal is to help narrow the gap between organ availability and the needs of many patients who are currently on the transplant waiting list.

Article J.Iske et al. Senolytics prevent mt-DNA-induced inflammation and promote the survival of aged organs following transplantation is published in the journal Nature Communications. 

Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru according to Brigham and Women's Hospital: Rejuvenating old organs could increase donor pool.