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Title: | THE RENAL EPIGENETIC CLOCK IS A BETTER SURROGATE FOR KIDNEY AGE THAN TELOMERE ATTRITION | Authors: | HEYLEN, Line Katrien, De Vusser Bernard, Thienpont Sprangers, Ben Kuypers, Dirk NAWROT, Tim Lambrechts, Diether Naesens, Maarten |
Issue Date: | 2019 | Publisher: | OXFORD UNIV PRESS | Source: | 56th Congress of the European-Renal-Association (ERA)-European-Dialysis-and-Transplant-Association (EDTA) - Burden, Access and Disparities in Kidney Disease, Budapest, HUNGARY, JUN 13-16, 2019 | Abstract: | INTRODUCTION: Chronological age is a major risk factor for many common diseases including kidney diseases and renal transplantation. Aging has however proven difficult to dissect given the many alterations at the molecular, cellular and tissue level. One of the hallmarks of replicative aging (senescence) is telomere attrition. Recently, the concept of an epigenetic clock, that predicts chronological age based on DNA methylation, was defined. In this study, we aimed to describe the relations between renal telomere length and the renal epigenetic clock in two cohorts of kidney biopsies performed at the time of transplantation, and the association with renal histology. METHODS: DNA methylation was measured genome-wide at >450,000 CpGs using the Illumina EPIC and 450K arrays in two cohorts of renal transplant biopsies (n=95 at implantation, and n= 67 post-reperfusion). Donor age ranged from 16 to 79 years in both cohorts. The epigenetic clock was calculated using the Horvath formula. Telomere length was measured in the majority of biopsies (78% implantation cohort and 79% post-reperfusion cohort). Epigenetic age acceleration (older epigenetic age in comparison to chronological age) was defined by the residuals to the linear regression curve of donor age to the epigenetic clock. Renal biopsies were scored according to the Banff classification at baseline, and 3 months and 12 months after transplantation. RESULTS: As previously reported, telomere length correlated with donor age, but the correlation was relatively weak (implantation cohort: r=-0.37, p=0.001 and postreperfusion cohort: r=-0.25, p = 0.07). In contrast, the epigenetic clock correlated strongly with age, at r=0.93, r=0.94, respectively and p<10^-15 for both cohorts. Epigenetic age acceleration did not correlate with telomere length (p=0.90 and p=0.48), suggesting that epigenetic aging and replicative aging are seperate entities, ticking at different clocks. Interestingly, in both cohorts the epigenetic clock overestimated the age of young donors. The epigenetic clock behaved also as chronological age in its correlation to several histological hallmarks of renal aging, in contrast to telomere length, which was less correlated to aging-associated histopathological lesions. CONCLUSIONS: The renal epigenetic clock acts as a surrogate for chronological age with high accuracy, and also reflects renal histolopathological lesions. For the first time, we describe that accelerated epigenetic aging does not correlate with telomere length, suggesting that renal epigenetic aging and renal replicative aging are separate entities driven by different factors. | Document URI: | http://hdl.handle.net/1942/30821 | ISSN: | 0931-0509 | e-ISSN: | 1460-2385 | DOI: | 10.1093/ndt/gfz106.FP334 | ISI #: | WOS:000495412900419 | Category: | C2 | Type: | Conference Material |
Appears in Collections: | Research publications |
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Heylen_Line.pdf Restricted Access | Conference material | 78.49 kB | Adobe PDF | View/Open Request a copy |
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