Drugs that clear away worn-out cells may improve the success of transplanted organs from older donors, according to research in mice.
As we get older, some cells stop dividing, but linger instead of dying off. These so-called senescent cells accumulate in our organs, releasing chemicals that can trigger inflammation and promote disease.
When an organ from an older donor is transplanted into a younger person, senescent cells in the transplanted organ can activate senescence in the recipient鈥檚 own cells. This 鈥渢ransfer鈥� of ageing can worsen the outcome of the transplantation or even elicit an immune response that results in rejection of the donated organ.
Advertisement
at Harvard Medical School and his colleagues have succeeded in stopping this transfer process in mice using senolytics, a new class of drugs that selectively clear away senescent cells. Their research will be presented at the European Society for Organ Transplantation Congress in Athens, Greece, on 18 September.
The team first transplanted hearts from old and young mice into young recipients. As expected, the mice that received hearts from older animals had greater numbers of senescent cells in their lymph nodes, muscles and organs compared with those that got hearts from younger animals.
Mice that received hearts from older animals also exhibited accelerated cognitive and physical decline. However, treating the older mice with the senolytic drugs dasatinib and quercetin before their organs were harvested significantly reduced the number of senescent cells found in the recipients after transplantation.
The animals that received old hearts treated with the drugs also matched recipients of young hearts in their cognitive performance and physical fitness.
鈥淭his is a promising approach with many potential implications,鈥� says at Imperial College London, although there are questions about how the findings will translate to humans. 鈥淸Human] donors might be dead, so in practical terms you might need to treat the organ itself before transplantation or the recipient, which might not be possible.鈥�
The number of people needing organ transplants is increasing, but organs are in short supply. Recent data shows that an average of 21 people die every day across Europe waiting for a transplant.
The age of the donor is a crucial factor determining the success of transplantation and so, despite this urgent need, organs from older donors are often turned down.
Gil says that although the findings don鈥檛 necessarily tell us anything new about ageing or senolytics, they offer 鈥渁 potentially very useful approach that could impact transplant recipients, and potentially increase the pool of organs that can be transplanted that, in the past, were rejected鈥�.
The researchers are now planning to investigate if their findings are applicable to humans. 鈥淲e will delve deeper into the mechanisms underpinning our current findings, with a particular focus on the potential role of senolytics in preventing the transfer of senescence in humans,鈥� says Tullius. He adds that the research 鈥渕ay not only help us to improve outcomes, but also make more organs available for transplantation鈥�.
