Scientists from Brigham & Women’s Hospital show that senolytics can rejuvenate organs from elderly donors by eliminating senescent cells and alleviating age-associated inflammation.
In a recent study published in Nature Communications, scientists from the Brigham and Women’s Hospital (Harvard Medical School) show that during aging, cell-free mitochondrial DNA (cf-mt-DNA) released by senescent cells accumulating in older organs activates the immune system .
Longevity.Technology: Although organs from elderly, deceased individuals could be used to meet the increasing demands in organ transplantation, their clinical use is limited by age-specific responses to injury and high immunogenicity, which pose significant threats to transplant patients and increase the risk of transplant rejection. Senolytics research could mitigate that risk as well as progressing understanding of the potential of senolytic drugs to combat aging.
Similarly, the study shows that tissue damage during ischemia reperfusion injury promotes cf-mt-DNA accumulation, which activates dendritic cells and induces age-associated chronic inflammation—also known as inflammaging .
Scientists went one step further and showed that organs from deceased, older individuals contain increased levels of cf-mt-DNA, providing clinical evidence of the link between aging, cf-mt-DNA, and activation of dendritic cell-mediated immune responses .
“… we are well prepared to take the next step toward clinical application by using a perfusion device to flow senolytic drugs over organs and measure whether or not there are improvements in levels of senescent cells …”
The scientists also found that treatment of old mice with senolytics (dasatinib and quercetin) eliminated senescent cells and cf-mt-DNA. Notably, the use of senolytics to target cf-mt-DNA release by senescent cells significantly alleviated inflammaging, rejuvenating old cardiac transplants and prolonging their survival.
“Older organs are available and have the potential to contribute to mitigating the current demand for organ transplantation,” said Dr Stefan Tullius, Professor at Harvard Medical School and corresponding author of the study . “If we can utilize older organs in a safe way with outcomes that are comparable, we will take a substantial step forward for helping patients.”
The findings of this study pinpointed cf-mt-DNA as a central player in inflammaging and provided evidence supporting the use of senolytics to extend the survival of transplants. However, clinical investigations are required to investigate the ability of senolytics to revitalise organs in humans, as well as the relevance of cf-mt-DNA accumulation in this process. Furthermore, future studies are required to test whether the treatment of organs with senolytics after being harvested from donors can also have a similar rejuvenating effect. The use of senolytics to promote Longevity by targeting cf-mt-DNA in aging organs is an exciting anti-aging strategy that merits further investigation.
“We have not yet tested the effects clinically, but we are well prepared to take the next step toward clinical application by using a perfusion device to flow senolytic drugs over organs and measure whether or not there are improvements in levels of senescent cells,” said Dr Tullius . “Our data provide a rationale for considering clinical trials treating donors, organs, and/or recipients with senolytic drugs to optimize the use of organs from older donors. The goal is to help to close the gap between organ availability and the needs of the many patients currently on transplant waiting lists.”