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Abstract

Introduction: Severe trauma(ST) is a cause of significant morbidity and mortality which is exacerbated in the elderly. Despite theories as to why this may be true, the exact cause has yet to be fully understood. We feel that this failure can be explained by the diversity of the host response to ST. The objective was to determine whether the elderly have unique genomic patterns in neutrophils in the acute/subacute periods after ST consistent with either ‘hyperinflammation’ or ‘immuno-senescence’ explaining the worse outcomes seen in the elderly. Methods: Microarray data collected in the Glue Grant from 34 severely traumatized adult patients were used to evaluate genome-wide expression from blood neutrophils on days 0.5, 1, 4, 7, 14, and 21 after ST. 17 elderly (≥55yo) and young (<55yo) patients with complicated ICU outcomes were matched based on gender and AIS score for comparison to non-injured controls (n=17). Subsequent analysis consisted of identifying differences in gene expression (p<0.001), individual fold gene changes (vs. control, p<0.05), gene ontologies, as well as functional pathways among elderly and young ST patients, and healthy subjects. Results: In the young, genome-wide expression patterns at 0.5 and 7 days were significantly more aberrant from control subjects than those in the elderly. Among 61 genes whose dysregulation is known to predict complicated outcomes after ST in young patients (CCM 2013 41(5):1175–85), we found that the aberrant genome expression was significantly less in the elderly populations at 0.5 and 1 days, and greater at 4 days. Fold changes in genes involved in inflammation, myeloid derived suppressor cells, and chemotaxis were also increased from control more in the young than the elderly at 0.5 days (Z>2.0). By day 4, young patients’ gene expression patterns appeared to return to baseline, while the dysregulated expression of the elderly patients persisted. The top canonical pathways involved in innate immunity in the young compared to elderly were significantly upregulated at 0.5 days and then downregulated by day 4. Conclusions: Our findings reveal a unique early genomic expression pattern of elderly patients after ST consistent with ‘immuno-senescence’. Initially, there is a diminished immune response compared to their younger counterparts, followed by prolonged up regulation of inflammatory genes associated with ‘hyperinflammation’. This research indicates that interventions to improve outcomes in the elderly will need to be distinct from younger cohorts, and address multiple components of protective immunity.