Data_Sheet_1_DNA Methylation - and Telomere - Based Biological Age Estimation as Markers of Biological Aging in Donors Kidneys.docx

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.

器官的生物学年龄或许可作为评估其质量的重要工具，尤其在老年群体中具有重要应用价值。本研究对同一受试者的肾脏[右肾（right kidney, RK）与左肾（left kidney, LK）]及血液白细胞（blood leukocytes）的生物学年龄进行了检测，并通过对比分析探讨血液是否能够反映肾脏的生物学衰老进程。本研究共纳入36名供者（中位年龄72岁，年龄范围19~92岁，男性占比42%），通过探索有丝分裂与非有丝分裂通路，采用端粒长度（telomere length, TL）、年龄相关甲基化变化（DNA甲基化年龄，DNAmAge）及其加速程度（AgeAcc）来评估生物学年龄。同一供者的右肾与左肾DNA甲基化年龄均高于血液的DNA甲基化年龄（右肾vs血液：p=0.0271；左肾vs血液：p=0.0245）；且右肾与左肾的年龄加速评分（AgeAcc）亦高于血液白细胞的对应评分（p=0.0271与p=0.0245），提示肾脏的年龄加速进程更快。而右肾与左肾的端粒长度（TL）则长于血液（p=0.0011与p=0.0098）；Remuzzi-Karpinski评分的升高与肾脏端粒损耗呈显著正相关（p=0.0046）。最后，血液与肾脏的端粒长度（TL，p<0.01）以及DNA甲基化年龄（DNAmAge，p<0.001）均存在显著相关性。上述生物学年龄标志物可在后续研究中作为评估供者器官质量的指标，有助于提高老年供者器官的临床使用率，从而为肾脏移植领域带来潜在的转化研究价值。