The gut and circulating virome: emerging players in aging and longevity

A growing body of evidence indicates that the human virome, comprising both the gut and circulating viral communities, plays a critical role in shaping host physiology across the lifespan. In the context of aging, this complex viral ecosystem is increasingly recognized as a key modulator of immune function, inflammation, and metabolic balance, with direct implications for healthspan and longevity. While much attention has traditionally focused on bacterial components of the microbiota, recent advances in metagenomics have uncovered age-related shifts in the composition and function of the virome, including expansion of specific bacteriophage families, reactivation of latent viruses, and the persistence of commensal viral pathobionts. These changes are tightly linked to immunosenescence, chronic inflammation, and neurodegeneration, hallmarks of unhealthy aging. Notably, centenarians appear to harbor a unique virome signature marked by increased viral diversity, enhanced lytic activity, and the enrichment of phage-encoded metabolic functions, suggesting a potential protective role in extreme longevity. Despite these insights, significant challenges remain in virome profiling, including technical biases, database limitations, and the vast proportion of taxonomically unassigned sequences known as "viral dark matter". This review highlights emerging data on the aging virome, underscores its relevance within the Geroscience framework, and discusses current barriers and future directions for translating virome research into clinical aging studies.