Immune Age, Cardiovascular Disease, and Anti-Viral Immunity

TL;DR

This paper explores how aging weakens both cardiovascular health and antiviral immunity, linking immune decline with chronic inflammation and disease.

Contribution

The paper proposes a novel framework connecting immune aging with cardiovascular disease and impaired antiviral responses.

Findings

Aging immune systems promote inflammation that worsens atherosclerosis.

Effective antiviral responses may worsen cardiovascular disease through immune cell exhaustion.

Atherosclerosis alters immune cell function, impairing both plaque control and antiviral defense.

Abstract

Cardiovascular morbidity and mortality rise precipitously during the 6th–9th decades of life, identifying aging as a critical risk factor. Simultaneously, older individuals are susceptible to severe viral infection, raising the question whether shared mechanisms exist that predispose to both cardiovascular disease (CVD) and failing anti-viral immunity. The aging process causes steady decline in immune fitness (immune aging), which undermines the ability to generate protective anti-viral immune responses. Paradoxically, the aging immune system supports unopposed inflammatory pathways (inflammaging), which exacerbates tissue inflammation in CVD, specifically atherosclerosis. Here, we review the current evidence of how innate and adaptive immune aging promotes tissue-destructive inflammation in atherosclerosis while failing to fight viral infections. Further, we consider how these two disease processes mutually influence each other. We propose that mounting an effective anti-viral response induces off-target bystander activation and exhausts immune cells, ultimately exacerbating CVD. Additionally, we explore how atherosclerotic CVD impacts innate immunity through epigenetic modification of hematopoietic precursors and metabolically conditioning immune cells, leading to a dysfunctional immune system that accelerates plaque inflammation while simultaneously impairing host defense.

Figures