S100A8/A9 as a central hub in inflammaging: Cross-system mechanisms

Area of Science:

• Biomedical Science
• Molecular Biology
• Gerontology

Background:

• Aging populations worldwide experience increased chronic inflammation, termed 'inflammaging'.
• The S100A8/A9 protein complex is implicated in a positive feedback loop exacerbating this aging-inflammation cycle.
• Understanding S100A8/A9's multifaceted roles is crucial for addressing age-related pathologies.

Purpose of the Study:

• To systematically review the structure, function, and system-specific roles of the S100A8/A9 complex.
• To explore the potential of S100A8/A9 as a biomarker for diagnosis, prognosis, and imaging.
• To evaluate therapeutic strategies targeting the S100A8/A9 pathway for anti-aging interventions.

Main Methods:

• Systematic literature review of S100A8/A9's extracellular and intracellular functions.
• Analysis of S100A8/A9's involvement in various organ systems including tumors, nervous, cardiovascular, metabolic, and muscular systems.
• Examination of S100A8/A9 as a biomarker and the efficacy of targeting strategies in preclinical models.

Main Results:

• S100A8/A9 regulates leukocyte adhesion, immune cell aggregation, inflammasome activation, and cell death pathways.
• Elevated S100A8/A9 expression correlates with immunosuppression, chemoresistance, neuroinflammation, cardiovascular aging, metabolic dysfunction, and muscle atrophy.
• S100A8/A9 levels serve as biomarkers for early diagnosis, risk stratification, and therapeutic resistance.
• Targeting the S100A8/A9 pathway shows promise in reducing inflammation and delaying disease progression in animal models.

Conclusions:

• S100A8/A9 is a central mediator linking aging, inflammation, and multi-system diseases.
• Interventions targeting S100A8/A9 pathways may offer novel strategies for extending healthspan.
• Further research into S100A8/A9 modulation could lead to practical anti-aging therapies.