Brain aerobic glycolysis is stable during adulthood: Direct evidence from cross-brain blood sampling in 239 healthy adults

The brain is a highly metabolic organ primarily fueled by glucose, and it is well established that a decline in cerebral glucose metabolism accompanies neurodegenerative disease. Recent work using positron emission tomography (PET) has demonstrated that cerebral glucose metabolism is also reduced in healthy aging which commences as early as 20 years of age, driven almost exclusively by reductions in non-oxidative glucose metabolism, that is, aerobic glycolysis. Given the historical variability and assumptions in PET-based interpretations regarding cerebral glucose metabolism with aging, we aimed to establish whether a drop in global aerobic glycolysis is truly a component of healthy aging in adulthood using direct measures of carbohydrates and oxygen across the human brain via invasive cross-brain blood sampling. We accumulated resting data from 17 studies comprising 239 healthy adults aged 19-45 years and show that aerobic glycolysis remains stable during aging based on a regression analysis of the arteriovenous differences for oxygen, glucose, and lactate, and their resultant ratios (oxygen glucose/carbohydrate indices). The direct cross-brain data presented here indicate that declining brain aerobic glycolysis is not a feature of normal brain aging during early-mid adulthood.