Frontiers in Medicine (Feb 2022)
Role of Age-Related Changes in DNA Methylation in the Disproportionate Susceptibility and Worse Outcomes of Sepsis in Older Adults
- Xiabing Lang,
- Xiabing Lang,
- Xiabing Lang,
- Xiabing Lang,
- Lingling Shen,
- Lingling Shen,
- Lingling Shen,
- Lingling Shen,
- Tingting Zhu,
- Tingting Zhu,
- Tingting Zhu,
- Tingting Zhu,
- Wenjun Zhao,
- Wenjun Zhao,
- Wenjun Zhao,
- Wenjun Zhao,
- Yang Chen,
- Yang Chen,
- Yang Chen,
- Yang Chen,
- Chaohong Zhu,
- Chaohong Zhu,
- Chaohong Zhu,
- Chaohong Zhu,
- Qun Su,
- Cuili Wang,
- Cuili Wang,
- Cuili Wang,
- Cuili Wang,
- Yucheng Wang,
- Yucheng Wang,
- Yucheng Wang,
- Yucheng Wang,
- Francesco Neri,
- Hong Jiang,
- Hong Jiang,
- Hong Jiang,
- Hong Jiang,
- Jianghua Chen,
- Jianghua Chen,
- Jianghua Chen,
- Jianghua Chen
Affiliations
- Xiabing Lang
- Kidney Disease Center, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
- Xiabing Lang
- Key Laboratory of Nephropathy, Hangzhou, China
- Xiabing Lang
- Institute of Nephropathy, Zhejiang University, Hangzhou, China
- Xiabing Lang
- Zhejiang Clinical Research Center of Kidney and Urinary System Disease, Hangzhou, China
- Lingling Shen
- Kidney Disease Center, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
- Lingling Shen
- Key Laboratory of Nephropathy, Hangzhou, China
- Lingling Shen
- Institute of Nephropathy, Zhejiang University, Hangzhou, China
- Lingling Shen
- Zhejiang Clinical Research Center of Kidney and Urinary System Disease, Hangzhou, China
- Tingting Zhu
- Kidney Disease Center, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
- Tingting Zhu
- Key Laboratory of Nephropathy, Hangzhou, China
- Tingting Zhu
- Institute of Nephropathy, Zhejiang University, Hangzhou, China
- Tingting Zhu
- Zhejiang Clinical Research Center of Kidney and Urinary System Disease, Hangzhou, China
- Wenjun Zhao
- Kidney Disease Center, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
- Wenjun Zhao
- Key Laboratory of Nephropathy, Hangzhou, China
- Wenjun Zhao
- Institute of Nephropathy, Zhejiang University, Hangzhou, China
- Wenjun Zhao
- Zhejiang Clinical Research Center of Kidney and Urinary System Disease, Hangzhou, China
- Yang Chen
- Kidney Disease Center, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
- Yang Chen
- Key Laboratory of Nephropathy, Hangzhou, China
- Yang Chen
- Institute of Nephropathy, Zhejiang University, Hangzhou, China
- Yang Chen
- Zhejiang Clinical Research Center of Kidney and Urinary System Disease, Hangzhou, China
- Chaohong Zhu
- Kidney Disease Center, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
- Chaohong Zhu
- Key Laboratory of Nephropathy, Hangzhou, China
- Chaohong Zhu
- Institute of Nephropathy, Zhejiang University, Hangzhou, China
- Chaohong Zhu
- Zhejiang Clinical Research Center of Kidney and Urinary System Disease, Hangzhou, China
- Qun Su
- Critical Care Medicine Department, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
- Cuili Wang
- Kidney Disease Center, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
- Cuili Wang
- Key Laboratory of Nephropathy, Hangzhou, China
- Cuili Wang
- Institute of Nephropathy, Zhejiang University, Hangzhou, China
- Cuili Wang
- Zhejiang Clinical Research Center of Kidney and Urinary System Disease, Hangzhou, China
- Yucheng Wang
- Kidney Disease Center, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
- Yucheng Wang
- Key Laboratory of Nephropathy, Hangzhou, China
- Yucheng Wang
- Institute of Nephropathy, Zhejiang University, Hangzhou, China
- Yucheng Wang
- Zhejiang Clinical Research Center of Kidney and Urinary System Disease, Hangzhou, China
- Francesco Neri
- Life Sciences and Systems Biology Department, University of Turin, Turin, Italy
- Hong Jiang
- Kidney Disease Center, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
- Hong Jiang
- Key Laboratory of Nephropathy, Hangzhou, China
- Hong Jiang
- Institute of Nephropathy, Zhejiang University, Hangzhou, China
- Hong Jiang
- Zhejiang Clinical Research Center of Kidney and Urinary System Disease, Hangzhou, China
- Jianghua Chen
- Kidney Disease Center, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
- Jianghua Chen
- Key Laboratory of Nephropathy, Hangzhou, China
- Jianghua Chen
- Institute of Nephropathy, Zhejiang University, Hangzhou, China
- Jianghua Chen
- Zhejiang Clinical Research Center of Kidney and Urinary System Disease, Hangzhou, China
- DOI
- https://doi.org/10.3389/fmed.2022.822847
- Journal volume & issue
-
Vol. 9
Abstract
Sepsis, a complex multisystem disorder, is among the top causes of hospitalization and mortality in older adults. However, the mechanisms underlying the disproportionate susceptibility to sepsis and worse outcomes in the elderly are not well understood. Recently, changes in DNA methylation have been shown to be linked to aging processes and age-related diseases. Thus, we postulated that age-related changes in DNA methylation may play a role in the onset and prognosis of sepsis in elderly patients. Here, we performed genome-wide methylation profiling of peripheral blood from patients with sepsis and controls. Among the CpG sites whose methylation changes may contribute to an increase in sepsis susceptibility or mortality, 241 sites that possessed age-related changes in DNA methylation in controls may partly explain the increased risk of sepsis in older adults, and 161 sites whose methylation significantly correlated with age in sepsis group may be the potential mechanisms underlying the worse outcomes of elderly septic patients. Finally, an independent cohort was used to validate our findings. Together, our study demonstrates that age-related changes in DNA methylation may explain in part the disproportionate susceptibility and worse outcomes of sepsis in older adults.
Keywords