Aging exacerbates cardiac dysfunction and mortality in sepsis through enhancing TLR2 activity

Area of Science:

• Immunology
• Cardiovascular Biology
• Gerontology

Background:

• Sepsis disproportionately affects the elderly, leading to higher mortality.
• The mechanisms underlying age-related susceptibility and poor sepsis outcomes remain unclear.
• Toll-like receptor 2 (TLR2) is implicated in inflammatory responses.

Purpose of the Study:

• To investigate if aging exacerbates sepsis-induced cardiac dysfunction through a TLR2-dependent pathway.
• To determine the role of TLR2 in age-associated inflammatory responses during sepsis.

Main Methods:

• Cecal ligation and puncture (CLP) model of sepsis in young and old wild-type (WT) and TLR2 knockout (KO) mice.
• Left ventricle (LV) function assessed using pressure-volume microcatheterization.
• Myocardial and plasma levels of inflammatory cytokines (TNF-α, IL-1β, IL-6, MCP-1) measured via ELISA.

Main Results:

• Old WT mice exhibited more severe cardiac dysfunction and higher mortality post-sepsis compared to young WT mice.
• Septic old WT mice showed elevated myocardial and plasma inflammatory markers.
• TLR2 knockout attenuated aging-related inflammatory differences, improving cardiac function and survival in old septic mice.
• Administration of a TLR2 agonist worsened cardiac dysfunction in old WT mice.

Conclusions:

• Aging exacerbates sepsis-induced cardiac dysfunction and mortality.
• Elevated TLR2 activity in aging contributes to heightened inflammatory responses during sepsis, worsening cardiac outcomes.
• Targeting TLR2 may offer therapeutic benefits for sepsis in the elderly.