Objective:

To outline how aging affects the gut–liver–heart axis and contributes to coronary artery disease (CAD) through metabolic changes, particularly focusing on bile acid metabolism.

Approach:

• Integration of Evidence: The review integrates cellular, molecular, and clinical evidence to demonstrate the relationship between aging, bile acid metabolism, and CAD.
• Focus on Immunometabolic Remodeling: It discusses how aging leads to immunometabolic remodeling that sustains chronic vascular inflammation.
• Emerging Interventions: The review appraises potential immune–metabolic interventions for CAD prevention and therapy in older adults.

Key Findings:

• Aging is a strong independent risk factor for CAD, with traditional risk models failing to capture the full extent of risk in older populations.
• Cellular senescence and the senescence-associated secretory phenotype (SASP) contribute to chronic inflammation and CAD progression.
• Dysbiosis in the gut microbiota affects bile acid metabolism, leading to systemic inflammation and cardiovascular risk.
• Altered bile acid signaling impacts macrophage activation and vascular health, contributing to endothelial dysfunction, foam cell formation, plaque instability, and adverse cardiac remodeling.

Interpretation:

The review presents bile acid signaling as a critical link between aging, inflammation, and CAD.

Limitations:

• Most proposed interventions are currently supported only by preclinical or early-phase human data.

Conclusion:

The review emphasizes the interconnectedness of the gut, liver, and heart in the context of aging and CAD.