Normal brain aging is accompanied by intensification of free radical processes and compromised bioenergetics. Caloric restriction is expected to counteract these changes but the underlying protective mechanisms remain poorly understood. The present work aimed to investigate the intensity of oxidative stress and energy metabolism in the cerebral cortex comparing mice of different ages as well as comparing mice given one of two regimens of food availability: ad libitum versus every-other-day fasting (EODF). Levels of oxidative stress markers, ketone bodies, glycolytic intermediates, mitochondrial respiration, and activities of antioxidant and glycolytic enzymes were assessed in cortex from 6-, 12- and 18-month old C57BL/6J mice. The greatest increase in oxidative stress markers and the sharpest decline in key glycolytic enzyme activities was observed in mice upon the transition from young (6 months) to middle (12 months) age, with smaller changes occurring upon transition to old-age (18 months). Brain mitochondrial respiration showed no significant changes with age. A decrease in the activities of key glycolytic enzymes was accompanied by an increase in the activity of glucose-6-phosphate dehydrogenase suggesting that during normal brain aging glucose metabolism is altered to lower glycolytic activity and increase dependence on the pentose-phosphate pathway. Interestingly, levels of ketone bodies and antioxidant capacity showed a greater decrease in the brain cortex of females as compared with males. The EODF regimen further suppressed glycolytic enzyme activities in the cortex of old mice, and partially enhanced oxygen consumption and respiratory control in the cortex of middle aged and old males. Thus, in the mammalian cortex the major aging-induced metabolic changes are already seen in middle age and are slightly alleviated by an intermittent fasting mode of feeding.

正常的大脑衰老伴随着自由基过程的增强和生物能的下降。热量限制有望抵消这些变化，但对潜在的保护机制仍然知之甚少。本研究旨在研究大脑皮层中氧化应激和能量代谢的强度，比较不同年龄的小鼠，以及比较采用两种可用食物方案之一的小鼠：随意与每隔一天的禁食（EODF）。在6、12和18个月大的C57BL / 6J小鼠的皮层中评估了氧化应激标记物，酮体，糖酵解中间体，线粒体呼吸以及抗氧化剂和糖酵解酶活性的水平。在从年轻（6个月）到中年（12个月）的过渡期中，小鼠的氧化应激标记物增加最大，关键糖酵解酶活性最大下降，而在过渡到老年（18个月）时变化较小）。脑线粒体呼吸随年龄增长无明显变化。关键糖酵解酶活性的降低伴随着6磷酸葡萄糖脱氢酶活性的增加，这表明在正常的脑衰老过程中，葡萄糖代谢发生改变，从而降低了糖酵解活性并增加了对戊糖磷酸途径的依赖性。有趣的是，与男性相比，女性的酮体水平和抗氧化能力显示出女性大脑皮层的更大减少。EODF方案进一步抑制了老年小鼠皮质的糖酵解酶活性，并部分增强了中老年男性皮质的耗氧量和呼吸控制。因此，在哺乳动物皮层中，主要的衰老引起的代谢变化已在中年出现，并通过间歇性禁食方式稍微缓解。有趣的是，与男性相比，女性的酮体水平和抗氧化能力显示出女性大脑皮层的更大减少。EODF方案进一步抑制了老年小鼠皮质的糖酵解酶活性，并部分增强了中老年男性皮质的耗氧量和呼吸控制。因此，在哺乳动物皮层中，主要的衰老引起的代谢变化已在中年出现，并通过间歇性禁食方式稍微缓解。有趣的是，与男性相比，女性的酮体水平和抗氧化能力显示出女性大脑皮层的更大减少。EODF方案进一步抑制了老年小鼠皮质的糖酵解酶活性，并部分增强了中老年男性皮质的耗氧量和呼吸控制。因此，在哺乳动物皮层中，主要的衰老引起的代谢变化已在中年出现，并通过间歇性禁食方式稍微缓解。并部分提高中老年男性皮质的耗氧量和呼吸控制。因此，在哺乳动物皮质中，主要的衰老引起的代谢变化已经在中年出现，并且通过间歇性的禁食方式稍有缓解。并部分提高中老年男性皮质的耗氧量和呼吸控制。因此，在哺乳动物皮层中，主要的衰老引起的代谢变化已在中年出现，并通过间歇性禁食方式稍微缓解。