DNA Methylation-and Telomere-Based Biological Age Estimation as Markers of Biological Aging in Donors Kidneys

FRONTIERS IN MEDICINE(2022)

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摘要
The biological age of an organ may represent a valuable tool for assessing its quality, especially in the elder. We examined the biological age of the kidneys [right (RK) and left kidney (LK)] and blood leukocytes in the same subject and compared these to assess whether blood mirrors kidney biological aging. Biological age was studied in n = 36 donors (median age: 72 years, range: 19-92; male: 42%) by exploring mitotic and non-mitotic pathways, using telomere length (TL) and age-methylation changes (DNAmAge) and its acceleration (AgeAcc). RK and LK DNAmAge are older than blood DNAmAge (RK vs. Blood, p = 0.0271 and LK vs. Blood, p = 0.0245) and RK and LK AgeAcc present higher score (this mean the AgeAcc is faster) than that of blood leukocytes (p = 0.0271 and p = 0.0245) in the same donor. TL of RK and LK are instead longer than that of blood (p = 0.0011 and p = 0.0098) and the increase in Remuzzi-Karpinski score is strongly correlated with kidney TL attrition (p = 0.0046). Finally, blood and kidney TL (p < 0.01) and DNAmAge (p < 0.001) were correlated. These markers can be evaluated in further studies as indicators of biological age of donor organ quality and increase the usage of organs from donors of advanced age therefore offering a potential translational research inkidney transplantation.
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关键词
kidney transplantation, DNA methylation age, telomere length, age acceleration, kidney rejuvenation, biological age
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