If there is no age for organ donation, transplants from the elderly put recipients at greater risk of rejection. But according to a new study, this risk could be reduced thanks to senolytic drugs, able to regenerate aging organs.

Rejuvenating grafts, soon possible?

A discovery that could “reduce the gap between supply and demand” in the

organ transplant. In a study published on August 27 in the journal Nature Communications, German, Japanese and American researchers have shown that the use of senolytic drugs could rejuvenate old grafts in mice.

More risk of rejection with old grafts

Organ donation is possible at any age. “Although the heart is rarely harvested in people over the age of 60, there are other organs, such as the kidneys or the liver that can be harvested in much older people.”, Specifies the Ministry of Health1. A real advantage, when we know that the world population is aging and the

need for growing grafts. But old transplants tend to induce a stronger alloimmune response than those from younger people, exposing recipients to more risks of

rejection and therefore death.

Senolytic drugs can rejuvenate transplants

This is where senolytic drugs come in. These molecules that attack senescent cells offer real hope against aging in the body. With age, senescent (aging) cells accumulate and are no longer destroyed by the body. In addition, they release acellular mitochondrial DNA (cf-mt-DNA) which causes an inflammatory reaction. The researchers therefore administered a combination of senolytics,

dasatinib and quercetin, to old mice to see the effects.

The results showed that after treatment, the skin and heart of donor rodents had significantly lower levels of acellular mitochondrial DNA and pro-inflammatory cells. The researchers also observed that the mice that received a heart transplant from the old mice treated with senolytics had survival rates comparable to those that received a transplant from younger rodents. 80% of donors were alive at 100 days, while organs from old, untreated mice stopped functioning on average 37 days later.

An “important step forward to help patients”

If these results must now be demonstrated in humans, the researchers say “ready“To move on to clinical application”using an infusion set to run senolytic drugs over the organs and measure the levels of senescent cells”. “If we can safely use old organs with comparable results, this will be an important step forward in helping patients”, Concludes Stefan Tullius, co-author of the study.

Created on 01 September 2020

Sources:

Iske, J., Seyda, M., Heinbokel, T. et al. Senolytics prevent mt-DNA-induced inflammation and promote the survival of aged organs following transplantation. Nat Commun 11, 4289 (2020). https://doi.org/10.1038/s41467-020-18039-x (

accessible online).

1 – The modalities of organ or tissue donation. Ministry of Health (

accessible online).