Chronic Infection and Cardiac Aging: a New Perspective on Pathogen-Associated Cardiomyopathy

Cardiovascular diseases remain the primary driver of global mortality, with advanced age serving the most significant risk factor for their development and progression. Emerging evidence suggests that chronic infections can act as potent catalysts for cardiac decline by prematurely inducing aging phenotypes. Pathogens, including viruses, bacteria, and parasites, that evade host clearance establish a state of permanent inflammaging: a chronic, low-grade inflammatory milieu characterized by persistent cytokine signaling and leukocyte infiltration. This environment directly mirrors the sterile inflammation that drives natural senescence. Mechanistically, chronic infection subverts the heart's homeostatic pathways, triggering cardiomyocyte senescence through the dysregulation of mTOR signaling and the impairment of autophagy. These infections further drive mitochondrial dysfunction and the overproduction of reactive oxygen species (ROS), leading to oxidative DNA damage and metabolic exhaustion within the myocardium. On a structural level, immune subversion, via macrophage polarization and the induction of autoimmunity, accelerates left ventricular hypertrophy, myocardial remodeling, and interstitial fibrosis. By characterizing chronic infection as a modifiable driver of biological aging, we can prioritize anti-infective strategies as essential components of cardiovascular longevity and geriatric care.