Can Herpesvirus Infections Influence When and How We Age?

Aging is accompanied by numerous interlinked cellular, genetic, and molecular changes, one of the most consequential being inflammaging: a chronic, low-grade systemic inflammatory state linked to metabolic dysregulation and pleiotropic effects on immune function. Although diverse intrinsic and extrinsic factors are known to drive inflammaging, the contribution of persistent viral infection remains incompletely understood. Here, we evaluate evidence that human herpesviruses, including cytomegalovirus (CMV), Epstein-Barr virus (EBV), herpes simplex viruses (HSV-1/2), and varicella zoster virus (VZV), may act as chronic antigenic and inflammatory stimuli capable of amplifying inflammaging and shaping the trajectory of aging. We review the molecular, cellular, and systems-level mechanisms by which herpesvirus latency and periodic reactivation sustain innate and adaptive immune activation, promote cellular senescence, and contribute to immune dysregulation and exhaustion. We further examine epidemiological evidence linking herpesvirus infection to dementia and other age-associated outcomes and highlight emerging data suggesting that antiviral treatment and vaccination, such as against VZV, may mitigate these effects. We conclude that herpesviruses are best understood as adjuvant contributors, rather than primary drivers, of inflammaging, and propose that persistent herpesvirus infection be considered an addressable risk factor in strategies aimed at promoting healthy aging.