Endogenous and Exogenous Viruses as Causal Factors in Aging: A Hypothesis

Abstract

Aging is characterized by the progressive accumulation of cellular damage and dysregulation across multiple systems. Hallmarks of aging such as genomic instability, chronic inflammation (“inflammaging”), cellular senescence, and epigenetic alterations contribute to functional decline and age-related diseases. Here we propose a unifying hypothesis: that viral elements, both endogenous and exogenous, act as active drivers of these aging processes. In this view, endogenous retroviruses (ERVs) reawakening within our genomes and chronic infections by exogenous viruses each initiate molecular and cellular cascades that causally accelerate aging. The central hypothesis is that age-related loss of control over these viral elements leads to their reactivation or persistent activity, which in turn induces hallmark aging phenotypes (DNA damage, inflammation, senescence, etc.), thereby driving organismal aging. We frame this hypothesis in light of emerging evidence and outline experimental approaches to test the idea. This hypothesis, if confirmed, suggests that treating aging may require not only cellular rejuvenation strategies but also antiviral interventions.