Transplanting older organs into younger recipients accelerates physical and cognitive decline by spreading cellular senescence, driven by factors like mitochondrial DNA. Treating donor organs with senolytics before transplantation reduces this impact, offering a promising strategy to improve health outcomes.
March 2024 – American Journal of Transplantation
Key takeaways
- Old organs spread cellular ageing: Transplanting older donor organs into younger recipients increases senescent cell burden in multiple tissues, including liver, muscle, and lymph nodes. This cellular ageing is not localised to the transplanted organ but spreads systemically, mimicking age-related decline and illustrating how biological age, not just function, impacts transplant outcomes
- Physical and cognitive decline follows transplant: Recipients of older organs displayed significant impairments in grip strength, coordination, and memory. These effects mirror the frailty and cognitive changes seen in natural ageing, suggesting that exposure to aged tissues alone is enough to accelerate decline, even in previously healthy, younger individuals
- Senescence driven by mitochondrial DNA: Mitochondrial DNA released from old donor tissues was identified as a key driver of senescence in transplant recipients. Injecting mitochondrial DNA alone into mice reproduced many of the physical and cognitive deficits, highlighting it as a critical biomarker and possible intervention point for transplant-induced ageing
- Senolytics may reverse transplant ageing: Administering senolytics such as dasatinib and quercetin to old donor mice before organ retrieval significantly reduced mitochondrial DNA release and improved recipient function. This suggests a preventative therapeutic strategy that could preserve vitality in transplant recipients and enhance the viability of older donor organs
Read the article at: Iske, Jasper, et al. “Transplanting Old Organs Promotes Senescence in Young Recipients.” American Journal of Transplantation, vol. 24, 2024, pp. 391–405. https://doi.org/10.1016/j.ajt.2023.10.013.
