Septic Shock in Advanced Age: Transcriptome Analysis Reveals Altered Molecular Signatures in Neutrophil Granulocytes.

Diogo Vieira Da Silva Pellegrina,Hermes Vieira Barbeiro,Eduardo Moraes Reis,Fabiano Pinheiro Da Silva,Irineu Tadeu Velasco,Patricia Severino,Flávia Maziero Andreghetto,Heraldo Possolo De Souza,Marcel Cerqueira César Machado,Cordula M Stover

doi:10.1371/journal.pone.0128341

Abstract

Sepsis is one of the highest causes of mortality in hospitalized people and a common complication in both surgical and clinical patients admitted to hospital for non-infectious reasons. Sepsis is especially common in older people and its incidence is likely to increase substantially as a population ages. Despite its increased prevalence and mortality in older people, immune responses in the elderly during septic shock appear similar to that in younger patients. The purpose of this study was to conduct a genome-wide gene expression analysis of circulating neutrophils from old and young septic patients to better understand how aged individuals respond to severe infectious insult. We detected several genes whose expression could be used to differentiate immune responses of the elderly from those of young people, including genes related to oxidative phosphorylation, mitochondrial dysfunction and TGF-β signaling, among others. Our results identify major molecular pathways that are particularly affected in the elderly during sepsis, which might have a pivotal role in worsening clinical outcomes compared with young people with sepsis.

Highlights

Sepsis is a complex syndrome triggered by infection and characterized by the massive deregulation of immunological networks [1]
A smaller fraction of long noncoding RNAs (lncRNA) (10%) was detected compared with protein-coding mRNAs (82%) (Table 1), which is in line with the more tissue-specific and less abundant nature of these transcripts [35, 36]
There is great hope that high-throughput screening technology will result in a better understanding of the complexity of systemic inflammation, identifying new therapeutic targets and groups of patients that may benefit from specific interventions

Summary

Introduction

Sepsis is a complex syndrome triggered by infection and characterized by the massive deregulation of immunological networks [1]. Septic patients have a mean age of approximately 65 years [2] and the incidence of sepsis and its risk of mortality increase significantly with advanced age [3, 4]. Factors that might contribute to the increased risk and incidence in the elderly include defects in the integrity of epithelial barriers, decreased gag and cough reflexes, altered levels of consciousness, immobility, concomitant medical diseases, a dependency on invasive medical devices, diminished physiological reserves, endocrine deficiencies, and malnutrition [5, 6]. Septic Shock in Advanced Age: Transcriptome Analysis from FAPESP (2014/03150-6) and EMR received an established investigator fellowship from CNPq

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