Aging impairs vaccine efficacy through two interconnected mechanisms: declining gut microbial diversity that reduces protective metabolites, and dysregulated mTOR signaling that suppresses immune memory formation. Restoring this microbiota-mTOR axis through targeted interventions offers a tractable strategy to improve vaccine responses in older adults.
Key Points
- Gut dysbiosis reduces short-chain fatty acids, exacerbating age-related inflammation
- mTOR hyperactivation suppresses autophagy and impairs T/B cell function
- mTOR inhibitors combined with microbiota modulation may restore vaccine efficacy
Longevity Analysis
Vaccine failure in aging reflects a specific breakdown in how the body recognizes and mounts sustained immune responses—not a global decline, but a dysfunction in the conversation between microbial ecology and cellular signaling. The microbiota produces short-chain fatty acids that normally constrain mTOR activity; when diversity collapses, this protective metabolite production falls, allowing mTOR to overactivate and suppress the precise immune memory needed for vaccine protection. This creates a feedback loop where dysregulated mTOR further degrades microbial composition. Rather than treating aging as inevitable immune decay, this framework identifies discrete, modifiable nodes: restoring microbial diversity through dietary or probiotic intervention, and pharmacologically constraining mTOR overactivation. The practical implication is that vaccine optimization in older populations may require decoding what's actually happening at the microbiota-immune interface before vaccination—and
Original published by Wiley Aging Cell, by Jiaxuan Li, Yuhong Zhang, Daijun Yu, Jianhua Li, Keda Chen, Lisheng Chu .