Gut microbes fuel aging tied to mitochondrial defects in mice

In PolgAmut accelerated-aging mice, researchers examined bi-directional interactions between gut microbes and host mitochondria during immune regulation, healthspan, and lifespan. They found that mitochondrial dysfunction accelerated the decline of gut microbiota structure over time. This mitochondrial defect also triggered immune dysregulation and inflammation through metabolic reprogramming of myeloid cells. Concurrently, the gut microbiota drove a paradoxical energy state by lowering mitochondrial function systemically while activating energy-intensive programs, such as immune remodeling and protein synthesis, through mTOR signaling. The authors propose that aging develops from an imbalance between microbiota-driven energetic demand and declining mitochondrial energy supply.