Predicting exacerbation of renal function by DNA methylation clock and DNA damage of urinary shedding cells: a pilot study

Abstract Recent reports have shown the feasibility of measuring biological age from DNA methylation levels in blood cells from specific regions identified by machine learning, collectively known as the epigenetic clock or DNA methylation clock. While extensive research has explored the association o...

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Main Authors: Akihito Hishikawa, Erina Sugita Nishimura, Norifumi Yoshimoto, Ran Nakamichi, Eriko Yoshida Hama, Wataru Ito, Tomomi Maruki, Kengo Nagashima, Ryoko Shimizu-Hirota, Hiromasa Takaishi, Hiroshi Itoh, Kaori Hayashi
Format: Article
Language:English
Published: Nature Portfolio 2024-05-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-024-62405-4
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author Akihito Hishikawa
Erina Sugita Nishimura
Norifumi Yoshimoto
Ran Nakamichi
Eriko Yoshida Hama
Wataru Ito
Tomomi Maruki
Kengo Nagashima
Ryoko Shimizu-Hirota
Hiromasa Takaishi
Hiroshi Itoh
Kaori Hayashi
author_facet Akihito Hishikawa
Erina Sugita Nishimura
Norifumi Yoshimoto
Ran Nakamichi
Eriko Yoshida Hama
Wataru Ito
Tomomi Maruki
Kengo Nagashima
Ryoko Shimizu-Hirota
Hiromasa Takaishi
Hiroshi Itoh
Kaori Hayashi
author_sort Akihito Hishikawa
collection DOAJ
description Abstract Recent reports have shown the feasibility of measuring biological age from DNA methylation levels in blood cells from specific regions identified by machine learning, collectively known as the epigenetic clock or DNA methylation clock. While extensive research has explored the association of the DNA methylation clock with cardiovascular diseases, cancer, and Alzheimer's disease, its relationship with kidney diseases remains largely unexplored. In particular, it is unclear whether the DNA methylation clock could serve as a predictor of worsening kidney function. In this pilot study involving 20 subjects, we investigated the association between the DNA methylation clock and subsequent deterioration of renal function. Additionally, we noninvasively evaluated DNA damage in urinary shedding cells using a previously reported method to examine the correlation with the DNA methylation clock and worsening kidney function. Our findings revealed that patients with an accelerated DNA methylation clock exhibited increased DNA damage in urinary shedding cells, along with a higher rate of eGFR decline. Moreover, in cases of advanced CKD (G4-5), the DNA damage in urinary shedding cells was significantly increased, highlighting the interplay between elevated DNA damage and eGFR decline. This study suggests the potential role of the DNA methylation clock and urinary DNA damage as predictive markers for the progression of chronic kidney disease.
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spelling doaj-art-e4922e1bc6b94fd686f0cad4c9a6d5662025-01-05T12:23:55ZengNature PortfolioScientific Reports2045-23222024-05-0114111010.1038/s41598-024-62405-4Predicting exacerbation of renal function by DNA methylation clock and DNA damage of urinary shedding cells: a pilot studyAkihito Hishikawa0Erina Sugita Nishimura1Norifumi Yoshimoto2Ran Nakamichi3Eriko Yoshida Hama4Wataru Ito5Tomomi Maruki6Kengo Nagashima7Ryoko Shimizu-Hirota8Hiromasa Takaishi9Hiroshi Itoh10Kaori Hayashi11Division of Nephrology, Endocrinology and Metabolism, Department of Internal Medicine, Keio University School of MedicineDivision of Nephrology, Endocrinology and Metabolism, Department of Internal Medicine, Keio University School of MedicineDivision of Nephrology, Endocrinology and Metabolism, Department of Internal Medicine, Keio University School of MedicineDivision of Nephrology, Endocrinology and Metabolism, Department of Internal Medicine, Keio University School of MedicineDivision of Nephrology, Endocrinology and Metabolism, Department of Internal Medicine, Keio University School of MedicineDivision of Nephrology, Endocrinology and Metabolism, Department of Internal Medicine, Keio University School of MedicineDivision of Nephrology, Endocrinology and Metabolism, Department of Internal Medicine, Keio University School of MedicineBiostatistics Unit, Clinical and Translational Research Center, Keio University School of MedicineCenter for Preventive Medicine, Keio University School of MedicineCenter for Preventive Medicine, Keio University School of MedicineCenter for Preventive Medicine, Keio University School of MedicineDivision of Nephrology, Endocrinology and Metabolism, Department of Internal Medicine, Keio University School of MedicineAbstract Recent reports have shown the feasibility of measuring biological age from DNA methylation levels in blood cells from specific regions identified by machine learning, collectively known as the epigenetic clock or DNA methylation clock. While extensive research has explored the association of the DNA methylation clock with cardiovascular diseases, cancer, and Alzheimer's disease, its relationship with kidney diseases remains largely unexplored. In particular, it is unclear whether the DNA methylation clock could serve as a predictor of worsening kidney function. In this pilot study involving 20 subjects, we investigated the association between the DNA methylation clock and subsequent deterioration of renal function. Additionally, we noninvasively evaluated DNA damage in urinary shedding cells using a previously reported method to examine the correlation with the DNA methylation clock and worsening kidney function. Our findings revealed that patients with an accelerated DNA methylation clock exhibited increased DNA damage in urinary shedding cells, along with a higher rate of eGFR decline. Moreover, in cases of advanced CKD (G4-5), the DNA damage in urinary shedding cells was significantly increased, highlighting the interplay between elevated DNA damage and eGFR decline. This study suggests the potential role of the DNA methylation clock and urinary DNA damage as predictive markers for the progression of chronic kidney disease.https://doi.org/10.1038/s41598-024-62405-4
spellingShingle Akihito Hishikawa
Erina Sugita Nishimura
Norifumi Yoshimoto
Ran Nakamichi
Eriko Yoshida Hama
Wataru Ito
Tomomi Maruki
Kengo Nagashima
Ryoko Shimizu-Hirota
Hiromasa Takaishi
Hiroshi Itoh
Kaori Hayashi
Predicting exacerbation of renal function by DNA methylation clock and DNA damage of urinary shedding cells: a pilot study
Scientific Reports
title Predicting exacerbation of renal function by DNA methylation clock and DNA damage of urinary shedding cells: a pilot study
title_full Predicting exacerbation of renal function by DNA methylation clock and DNA damage of urinary shedding cells: a pilot study
title_fullStr Predicting exacerbation of renal function by DNA methylation clock and DNA damage of urinary shedding cells: a pilot study
title_full_unstemmed Predicting exacerbation of renal function by DNA methylation clock and DNA damage of urinary shedding cells: a pilot study
title_short Predicting exacerbation of renal function by DNA methylation clock and DNA damage of urinary shedding cells: a pilot study
title_sort predicting exacerbation of renal function by dna methylation clock and dna damage of urinary shedding cells a pilot study
url https://doi.org/10.1038/s41598-024-62405-4
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