Neonatal overfeeding accelerates age-related sarcopenia and metabolic disorders through lifelong gut mucosa and microbiota programming

To address this gap, we employed an established neonatal overfeeding model by reducing litter size, assigning litters to either 4 pups per dam (Overfed group) or 8 pups per dam (Normal-fed control group). To directly examine whether microbiota alterations mediate neonatal overnutrition-induced acceleration of sarcopenia, we performed fecal microbiota transplantation (FMT) experiments.

We transplanted microbiota from either aged normal-fed or overfed donor mice into adult recipients (rNormal and rOver groups) maintained on a high-fat diet (HFD) for 20 weeks to accelerate the onset of metabolic and muscular dysfunction. These findings reveal a developmental origin of age-related sarcopenia and define a gut-muscle axis linking childhood overnutrition to muscle aging.