In aged mice, influenza infection produced pronounced gut microbiota dysbiosis with depletion of short-chain fatty acid producers such as Akkermansia muciniphila and reduced microbial capacity for acetate production. In senescent human lung fibroblasts, acetate supplementation lowered viral replication and inflammatory signaling through FFAR2/FFAR3 receptors and increased histone H3 acetylation, identifying a metabolic and epigenetic route by which gut-derived metabolites support antiviral defense in aging tissue.
Key Points
- Aging depleted acetate-producing gut commensals during influenza infection in mice
- Acetate reduced viral replication and inflammation in senescent lung cells
- FFAR2/FFAR3 signaling and histone H3 acetylation mediated protection
Longevity Analysis
Respiratory vulnerability in older adults is partly a metabolic problem originating in the gut, where fermentation capacity declines and the signaling molecules that calibrate immune responses in distant tissue become scarce. Acetate acting through receptor binding and chromatin modification places fiber intake, microbial diversity, and anything that disrupts them — antibiotics, low-residue diets, chronic inflammatory load — upstream of how well the lungs defend themselves. Microbial composition becomes a readable marker of antiviral reserve rather than a digestive detail, and interventions that restore fermentative output have a plausible mechanism for reducing influenza severity with age.
Original published by Wiley Aging Cell, by Christoph Wernike, Antje Häder, Yasmina Reisser, Kiana Garakani, Franziska Hornung, Claude Jourdan Le Saux, Stefanie Deinhardt‐Emmer .