Does Donor Age Have Effects on Senescence Biomarkers in Kidney-Transplanted Patients?
Juan López-Pérez1,2, Juan Miguel Suarez-Rivero2, Inés Muela-Zarzuela3
1Department of Immunology, Puerta del Mar Hospital, Cádiz, Spain.
Abstract:
Renal transplantation is an effective treatment for severe chronic kidney diseases. However, young patients often face a scarcity of kidneys from donors of similar age, resulting in the transplantation of older organs, which increase the risk of graft rejection and several complications compared with older individuals who receive kidneys from donors of similar age or younger. This article focuses on studying different senescence biomarkers in donors and patients who received kidneys from various age ranges complying with the STROBE requirements. We studied 61 patients subjected to renal transplant isolating blood samples 24 h before, and 24 h, 3 days, 7 days, 3 months, and 6 months after transplant. The patients were divided into three groups: older donor than the patient (Old Donor), younger donor than the patient (Young Donor), and similar age (Matched). We studied different senescence markers such as p16, p21, interleukin 6 (IL-6), and senescence-associated secretory phenotype (SASP) release. Young patients who receive older organs showed increased mRNA and protein expression of the senescence makers. Hence, increased SASP release was also observed in patients from older donor. In contrast, older patients who receive younger organs showed a slow but consistent improvement in their initial senescent phenotype. In addition, macrophage cell model treated with blood-derived serum from patients 6 months after the transplant showed a pro-senescence environment in macrophages proposed by the SASP from the patients. These results lead the hypothesis that senolytics could reduce the presence of senescent cells and mitigate the complications associated with the transplantation of older organs in young patients.
Insights
Transplanting older kidneys into young patients increases senescence markers and complications. Senolytics may mitigate these issues by reducing senescent cells, improving outcomes in renal transplantation.
Area of Science:
- Nephrology
- Gerontology
- Immunology
Background:
- Renal transplantation is vital for chronic kidney disease.
- Young recipients often receive older donor kidneys, increasing rejection and complications.
- Donor-recipient age mismatch impacts graft outcomes.
Purpose of the Study:
- Investigate senescence biomarkers in renal transplant recipients and donors of varying age groups.
- Assess the impact of donor-recipient age disparity on senescence markers and SASP.
- Hypothesize senolytics as a potential therapeutic strategy.
Main Methods:
- Studied 61 renal transplant patients and donors across age-matched and mismatched groups.
- Collected blood samples pre-transplant and at multiple time points post-transplant.
- Analyzed senescence markers (p16, p21, IL-6) and senescence-associated secretory phenotype (SASP) via mRNA and protein expression.
Main Results:
- Young patients receiving older donor kidneys showed elevated senescence markers and SASP.
- Older patients receiving younger donor kidneys exhibited improved senescent phenotype.
- Post-transplant serum induced a pro-senescence environment in macrophages.
Conclusions:
- Donor-recipient age mismatch significantly influences senescence markers post-renal transplant.
- Older donor organs in young recipients promote a pro-senescence environment.
- Senolytics represent a promising therapeutic avenue to reduce complications from older donor organ transplantation.
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