Advanced Age in Mice Exacerbates Sepsis-Induced Inflammation, Vascular Permeability, and Multi-Organ Dysfunction

Area of Science:

• Immunology
• Gerontology
• Pathophysiology

Background:

• Sepsis is a life-threatening condition with high mortality in elderly individuals.
• Aging is associated with increased vulnerability to infections and poorer outcomes.
• Endothelial vascular permeability is a key feature of sepsis-induced organ damage.

Purpose of the Study:

• To investigate how advanced age impacts sepsis-induced inflammation and endothelial vascular permeability.
• To determine if aging delays recovery and prolongs organ injury in sepsis.
• To compare sepsis outcomes in young versus aged mice.

Main Methods:

• A polymicrobial sepsis model using cecal slurry (CS) injection in young (3-month) and aged (18-month) C57BL/6 mice.
• Assessment of physiological dysfunction, systemic and organ-specific inflammation, and endothelial injury during acute (24h) and recovery (8d) phases.
• Measurement of plasma TNF-α and kidney tissue NGAL as key inflammatory and injury markers.

Main Results:

• Aged mice showed significantly worse physiological dysfunction and higher systemic/organ-specific inflammation during the acute phase.
• Increased endothelial injury and vascular permeability were observed in aged mice compared to young mice.
• Aged mice exhibited sustained physiological dysfunction, prolonged inflammation, and persistent organ injury (kidney and liver) during the recovery phase.

Conclusions:

• Advanced age exacerbates sepsis severity, leading to increased inflammation and endothelial dysfunction.
• Aging significantly delays sepsis recovery and contributes to sustained organ injury.
• The findings underscore the importance of using aged animal models and evaluating multiple organs to develop targeted sepsis therapies for the elderly.