Aging-induced alterations in gene transcripts and functional activity of mitochondrial oxidative phosphorylation complexes in the heart
Aging-induced alterations in gene transcripts and functional activity of mitochondrial oxidative phosphorylation complexes in the heart
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DOI：
10.1016/j.mad.2008.02.010
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发表时间：
2008-06-01
影响因子：
5.3
通讯作者：
Jahangir, Arshad
中科院分区：
文献类型：
--
作者：
Preston, Claudia C.;Oberlin, Andrew S.;Jahangir, Arshad
衰老与能量储备的进行性下降有关，从而损害心脏性能和对损伤的耐受性。虽然在衰老的心脏线粒体功能的偏差已被证明，能量代谢下降的分子基础只被部分理解。在这里，高通量转录基因编码的成年（6个月）和老年（24个月）大鼠心室线粒体蛋白的基因进行了比较，使用微阵列。在614个编码线粒体蛋白质的基因中，有94个基因在老年人中差异表达，95%的基因表达下调。大多数变化影响编码参与氧化磷酸化（39）、底物代谢（14）和三羧酸循环（6）的蛋白质的基因。与成年人相比，老年心脏基因表达的变化转化为线粒体功能能力的降低，NADH-脱氢酶和F0 F1 ATP酶复合物活性以及氧利用和ATP合成能力的降低。编码参与线粒体代谢和生物发生调节的转录共激活因子的基因表达在老年心室中受到调节，而线粒体密度没有减少。因此，衰老诱导氧化磷酸化复合物I和V的活性在线粒体基因的更广泛的转录下调中选择性下降，为与衰老相关的能量效率降低提供了底物。(C)2008爱思唯尔爱尔兰有限公司保留所有权利。
Aging is associated with progressive decline in energetic reserves compromising cardiac performance and tolerance to injury. Although deviations in mitochondrial functions have been documented in senescent heart, the molecular bases for the decline in energy metabolism are only partially understood. Here, high-throughput transcription profiles of genes coding for mitochondrial proteins in ventricles from adult (6-months) and aged (24-months) rats were compared using microarrays. Out of 614 genes encoding for mitochondrial proteins, 94 were differentially expressed with 95% downregulated in the aged. The majority of changes affected genes coding for proteins involved in oxidative phosphorylation (39), substrate metabolism (14) and tricarboxylic acid cycle (6). Compared to adult, gene expression changes in aged hearts translated into a reduced mitochondrial functional capacity, with decreased NADH-dehydrogenase and F0F1 ATPase complex activities and capacity for oxygen-utilization and ATP synthesis. Expression of genes coding for transcription co-activator factors involved in the regulation of mitochondrial metabolism and biogenesis were clownregulated in aged ventricles without reduction in mitochondrial density. Thus, aging induces a selective decline in activities of oxidative phosphorylation complexes I and V within a broader transcriptional downregulation of mitochondrial genes, providing a substrate for reduced energetic efficiency associated with senescence. (C) 2008 Elsevier Ireland Ltd. All rights reserved.