The impact of hindlimb suspension on gastrointestinal integrity in aged rats: Segment-specific effects on inflammation and oxidative stress

Background: Aging compromises gastrointestinal integrity and increases inflammation, making the elderly more vulnerable to physiological stressors. Prolonged immobility due to bedrest, frailty, or simulated microgravity, may exacerbate these age-related effects. Despite growing concerns, the impact of immobility on the aging gastrointestinal tract remains largely unexplored. Methods: Aged (24 month-old) male Sprague–Dawley rats (n = 8 per group) were assigned to control or 14-day hindlimb suspension (HLS) conditions to simulate immobility. Histological and molecular analyses were conducted on the ileum and colon. Protein concentrations of key inflammatory mediators, nuclear factor kappa B (NF-κB), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and monocyte chemoattractant protein-1 (MCP-1), and the antioxidant enzyme superoxide dismutase (SOD) were quantified in tissue homogenates using enzyme-linked immunosorbent assay (ELISA). Results: HLS induced segment-specific changes; the ileum showed structural changes, with a 19 % reduction in villus height and 36 % thinning of the muscularis externa (p ≤ 0.002), accompanied by significant upregulation in NF-κB (3.9-fold) and IL-6 (11.8-fold) (p < 0.05). In contrast, the colon maintained histological integrity but exhibited increased NF-κB (66 %; p = 0.016), IL-6 (9.7-fold), MCP-1 (3.6-fold), and a twofold elevation in SOD (all p < 0.023). Conclusion: HLS induced segment-specific changes in the aged intestine, with atrophic and inflammatory alterations in the ileum and increased markers of inflammation and oxidative stress in the colon. These findings highlight the need for targeted interventions to preserve gastrointestinal health in immobilized elderly patients.