The TCA cycle as an oxidative and synthetic pathway is suppressed with aging in jejunal epithelial cells

The influence of aging on glucose and glutamine metabolism by isolated jejunal cells was studied using young (4 months) and aged (24 months) Fischer 344 male rats when fed ad libitum or fasted 48 h. Concentration-dependent oxidation of glucose ([14C(U)]glucose) followed Michaelis-Menten kinetics. Neither K(ox) nor Vmax was influenced by animal age or feeding status, but at 1 mM, glucose oxidation was significantly higher for aged than young fed animals. In all animal groups, glutamine reduced glucose oxidation by ca. 60%, glucose stimulated glutamine oxidation by ca. 25%, and succinate CO2 ratios ranged from 1.37 for 20 mM glucose to 5.46 for 20 mM glucose+glutamine. The probability that a substrate that enters the TCA cycle will either remain in the cycle for one complete turn or leave and reenter as acetyl-CoA averaged 0.85 for glucose, 0.36 for glutamine, and 0.31 for glucose+glutamine. In comparison with the young fed animals, cells from fed aged animals showed lower oxygen uptake in the absence and presence of exogenous substrate, lower glucose oxidation, lower entry of glucose and glutamine into the TCA cycle, and lower contribution of glucose and glutamine carbon to anaplerosis and subsequent synthetic compounds. Differences between the young and aged animals were more pronounced in cells from fed animals than from fasted animals.