The effect of age on the blood transcriptomic response in critical illness due to sepsis

Abstract

Sepsis, a life-threatening response to infection leading to global health challenges, disproportionately affects populations at the extremes of age, particularly the elderly. By focusing on both protein-coding and non-coding RNA species, this study aims to fill a significant research gap by examining the effects of ageing on the blood transcriptome response in sepsis patients. Utilising a comprehensive bioinformatics approach, publicly available genome-wide leucocyte transcriptomic datasets will be analysed, comprising 298 whole blood samples encompassing 82 healthy volunteers, 156 sepsis patients, and 59 non-infectious critically-ill patients. Our goals are to find age-specific transcriptomic signatures, compare transcriptome profiles between age groups, and investigate how ageing affects sepsis outcomes. By applying generalised linear models, mixed models and Gene Set Enrichment Analysis, the aim is to uncover underlying molecular mechanisms contributing to age-related differences in sepsis pathophysiology. This research is necessitated by the ageing global population and the substantial yet underreported burden of sepsis. In healthy individuals, ageing was associated with distinct transcriptomic changes, particularly in RNA processing and ribosomal function pathways. In contrast, sepsis appeared to override age-associated transcriptional patterns, with no significant DEGs observed across age groups under standard thresholds.