Immune surveillance and microbial escape in the aging host: Why does the microbiome lose its balance?

Abstract

Host-associated microbiomes are compositionally stable across most of the life span, yet undergo consistent and marked deterioration during aging, a phenomenon linked to metabolic dysfunction and disease. What drives this late-life collapse remains poorly understood, in part because the mechanisms by which hosts actively construct and maintain the microbial niche during adulthood remain incompletely characterized. This Unsolved Mystery integrates evidence from immunology and ecosystem ecology to investigate the role of immunosenescence in age-associated dysbiosis, raising the possibility of interventions that restore immune surveillance capacity alongside ecologically informed microbiome management, rather than targeting community composition in isolation.