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 characterized by a dysregulated immune response and increased vascular permeability, often leading to multi-organ failure.
• Elderly individuals face higher sepsis morbidity and mortality rates due to age-related immune system changes.

Purpose of the Study:

• To investigate how advanced age impacts sepsis-induced inflammation, endothelial vascular permeability, and organ injury.
• To determine if aging delays recovery and prolongs inflammation and organ damage in sepsis.

Main Methods:

• A polymicrobial sepsis model using cecal slurry (CS) injection in young (3-month-old) and aged (18-month-old) C57BL/6 mice.
• Assessment of physiological dysfunction, systemic and organ-specific inflammation, endothelial injury, vascular permeability, and kidney/liver function during acute (24-hour) and recovery (8-day) phases.

Main Results:

• Aged mice exhibited exacerbated physiological dysfunction, higher systemic and organ-specific inflammation, increased endothelial injury, and greater kidney/liver dysfunction during the acute phase compared to young mice.
• During recovery, aged mice showed sustained physiological dysfunction, prolonged inflammation, and persistent organ injury, particularly in the kidneys, compared to young mice.

Conclusions:

• Advanced age significantly worsens sepsis severity, outcomes, and recovery.
• The findings underscore the importance of utilizing aged animal models and conducting multi-organ evaluations to develop effective sepsis therapies for the elderly.