Glycocalyx and Metabolomic Profiles After Trauma Across Age and Frailty Groups: A Pilot Study.

INTRODUCTION: To study post injury metabolite activity and glycocalyx shedding in older adults (OAs) compared to younger adults (YAs). Changes in the metabolome and the glycocalyx after injury are increasingly understood in YAs, but not in OAs. METHODS: We performed a pilot study (2023-2024) at our level I trauma center. Plasma samples were obtained within 60 min of presentation and stratified by age (OAs ≥ 60 y and YAs < 60 y) and compared. Extracts were analyzed using liquid chromatography and mass spectrometry. Enzyme-linked immunosorbent assay testing measured glycocalyx biomarkers, syndecan-1, syndecan-4(Sdc-4), and high mobility group box 1(HMGB-1), and tissue inhibitor of metalloproteinase 2 (TIMP-2). Principal Coordinate Analysis and Orthogonal Projections to Latent Structures Discriminant Analysis were used to characterize and compare metabolomic profiles between groups. RESULTS: Seventy-nine patients were enrolled: 60 OAs and 19 YAs. The median age was 71, majority were male (51%) and White (91%), with 15 (19%) frail patients. OAs had a significantly different post injury metabolite profile compared to YAs (permutational multivariate analysis of variance (PERMANOVA) P < 0.001). There were 30 key metabolites that showed age-specific correlations with glycocalyx markers. Of these, 22 metabolites had strong negative correlations with Sdc-4 in YA (Pearson r < -0.9, P < 0.05). These metabolites had moderate negative correlations with TIMP-2 in OAs (Pearson r = -0.5 to -0.9, P < 0.05). Sdc-4 was significantly different between frail versus nonfrail patients (P = 0.0068). TIMP-2 was significantly higher in OAs compared to YAs (P = 0.01). CONCLUSIONS: Older and frail trauma patients demonstrated different glycocalyx biomarker and plasma metabolomic profiles following injury. TIMP-2 appears more closely associated with chronological age, whereas syndecan-4 differences were more strongly associated with frailty status. These exploratory findings suggest biologic heterogeneity in post injury responses and support the need for larger studies examining age- associated and frailty-associated endothelial-metabolic interactions after trauma. Correlation patterns suggest age-specific shedding mechanisms after injury serving as potential targets for age-directed resuscitation.