Bulk RNA-sequencing of 66 human donor livers found that grafts from donation after circulatory death carry markedly higher senescence-associated and inflammatory transcriptional signatures than those from donation after brain death, confirmed by p16 and p21 immunohistochemistry. The ischemic injury sustained during procurement appears to induce senescence programs that persist in the tissue at the time of transplant. Senolytic or senomorphic intervention before implantation is proposed as a modifiable target to improve graft quality and recipient outcomes.
Key Points
- Circulatory-death livers show elevated senescence and inflammatory gene signatures versus brain-deat
- 1,548 differentially expressed genes separated the two donor types; p16 staining confirmed
- Procurement-related ischemic injury induces senescence programs potentially targetable before transp
Longevity Analysis
Senescence is treated here as an acute, injury-induced state rather than a slow consequence of chronological aging, measurable within hours of organ procurement. That distinction broadens the therapeutic window for senolytics and senomorphics beyond age-related disease into acute ischemic injury, where machine perfusion offers a direct route for ex vivo drug delivery. With donor populations aging and marginal grafts increasingly used, quantifying senescent burden may become a practical measure of tissue quality.
Original published by Wiley Aging Cell, by Adam M. Thorne, Sabrina Stimmeder, Kirill Ustyantsev, Niels Mulder, Laura Niedernhofer, Ton Lisman, Marco Demaria, Eugene Berezikov, Folkert Kuipers, Vincent E. de Meijer .