Chronic D-Galactose Accelerates Aging-Like Decline in Aerobic Capacity and Cognitive Function Through Inflammation and Oxidative Stress in Central and Peripheral Tissues

Introduction: D-galactose (D-GAL) is an aldohexose naturally present in the body and diet; however, chronic exposure can be deleterious to health and promote aging-related changes. Thus, the effects of D-GAL on aerobic capacity and cognitive function based on central and peripheral hallmarks remain unclear. This study investigated the effects of chronic D-GAL administration on physical performance, memory, inflammatory markers, and oxidative stress in the brain and skeletal muscle of rats. Methods: Male Wistar rats received D-galactose (150 mg·kg⁻¹·day⁻¹) administered intraperitoneally for eight weeks. Muscle strength was assessed using a vertical ladder test, whereas aerobic capacity was evaluated by treadmill testing at weeks 4 and 8. Memory was analyzed using the Novel Object Recognition Test. Biochemical analyses were performed in central and peripheral tissues, including the soleus, extensor digitorum longus (EDL) muscles, hippocampus, and frontal cortex. Results: D-galactose reduced aerobic performance, evidenced by decreased VO₂peak (p = 0.044) and work output (p = 0.011) at week 4, with a further decline in work output at week 8. Chronic D-galactose also impaired long-term memory. Oxidative stress increased, with elevated hydroperoxides in the EDL (p = 0.010) and hippocampus (p = 0.040), and higher TBARS levels in the hippocampus (p = 0.020). Inflammatory modulation was observed, with reduced IL-10 levels in the soleus (p = 0.040), hippocampus (p < 0.001), and frontal cortex (p = 0.044). Conclusion: Chronic D-galactose–induced aging impairs aerobic capacity and memory and is associated with increased oxidative stress and inflammation in skeletal muscle and brain tissue overall in rats.