Role of Age-Related Changes in DNA Methylation in the Disproportionate Susceptibility and Worse Outcomes of Sepsis in Older Adults.

Xiabing Lang,Jianghua Chen,Wenjun Zhao,Yucheng Wang,Qun Su,Chaohong Zhu,Tingting Zhu,Francesco Neri,Lingling Shen,Cuili Wang,Yang Chen,Hong Jiang

doi:10.3389/fmed.2022.822847

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.

Highlights

Sepsis, a life-threatening organ dysfunction characterized by a dysregulated host response to infection, is a leading cause of morbidity and mortality among critically ill patients [1]
To investigate the epigenetic changes in sepsis, genomewide methylation profiling was performed in peripheral blood from 24 sepsis patients aged 16–88 years, and 12 healthy controls aged 22–84 years
Batch correction, and normalization, a total of 8,437 CpG sites which significantly differentially methylated between sepsis and control group were identified as methylation variable positions (MVPs)

Summary

Introduction

A life-threatening organ dysfunction characterized by a dysregulated host response to infection, is a leading cause of morbidity and mortality among critically ill patients [1]. The incidence of sepsis is expected to increase, likely due to the aging of our population [2, 3]. More than 60% of sepsis occur in patients aged ≥65 years, and about 60% of in-hospital mortality from sepsis occur in this age group [4, 5]. Aging has been recognized as the primary risk factor for developing sepsis [6]. The underlying mechanisms of the disproportionate susceptibility to sepsis and worse outcomes in older adults are not yet fully understood.

Methods

Results

Conclusion