Department of Diagnostic Radiology, Yale School of Medicine, New Haven, Connecticut 06520-8020, USA.
J Cereb Blood Flow Metab. 2010 Jan;30(1):211-21. doi: 10.1038/jcbfm.2009.197. Epub 2009 Sep 30.
A decline in brain function is a characteristic feature of healthy aging; however, little is known about the biologic basis of this phenomenon. To determine whether there are alterations in brain mitochondrial metabolism associated with healthy aging, we combined (13)C/(1)H magnetic resonance spectroscopy with infusions of [1-(13)C]glucose and [2-(13)C]acetate to quantitatively characterize rates of neuronal and astroglial tricarboxylic acid cycles, as well as neuroglial glutamate-glutamine cycling, in healthy elderly and young volunteers. Compared with young subjects, neuronal mitochondrial metabolism and glutamate-glutamine cycle flux was approximately 30% lower in elderly subjects. The reduction in individual subjects correlated strongly with reductions in N-acetylaspartate and glutamate concentrations consistent with chronic reductions in brain mitochondrial function. In elderly subjects infused with [2-(13)C]acetate labeling of glutamine, C4 and C3 differed from that of the young subjects, indicating age-related changes in glial mitochondrial metabolism. Taken together, these studies show that healthy aging is associated with reduced neuronal mitochondrial metabolism and altered glial mitochondrial metabolism, which may in part be responsible for declines in brain function.
大脑功能的下降是健康衰老的一个特征；然而，人们对这一现象的生物学基础知之甚少。为了确定与健康衰老相关的大脑线粒体代谢是否存在改变，我们结合 (13)C/(1)H 磁共振波谱和 [1-(13)C]葡萄糖和 [2-(13)C]乙酸的输注，定量描述健康老年和年轻志愿者神经元和星形胶质细胞三羧酸循环以及神经胶质谷氨酸-谷氨酰胺循环的速率。与年轻受试者相比，老年受试者的神经元线粒体代谢和谷氨酸-谷氨酰胺循环通量约低 30%。个体受试者的减少与 N-乙酰天冬氨酸和谷氨酸浓度的减少密切相关，这与大脑线粒体功能的慢性降低一致。在输注 [2-(13)C]乙酸的老年受试者中，谷氨酰胺的 C4 和 C3 标记与年轻受试者不同，表明与年龄相关的神经胶质线粒体代谢发生变化。总之，这些研究表明，健康衰老与神经元线粒体代谢降低和神经胶质线粒体代谢改变有关，这可能部分是大脑功能下降的原因。
