title: Aging-induced alterations in gene transcripts and functional activity of mitochondrial oxidative phosphorylation complexes in the heart.
abstract: 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 F(0)F(1) 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 downregulated 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.
authors.affiliation: Marriot Heart Disease Research Program, Department of Medicine, Mayo Clinic, Rochester, MN 55905, United States.
authors.forename: Claudia C
authors.initials: CC
authors.lastname: Preston
authors.forename: Andrew S
authors.initials: AS
authors.lastname: Oberlin
authors.forename: Ekhson L
authors.initials: EL
authors.lastname: Holmuhamedov
authors.forename: Anu
authors.initials: A
authors.lastname: Gupta
authors.forename: Sandeep
authors.initials: S
authors.lastname: Sagar
authors.forename: Rashad H Khazi
authors.initials: RH
authors.lastname: Syed
authors.forename: Sabeeh A
authors.initials: SA
authors.lastname: Siddiqui
authors.forename: Sreekumar
authors.initials: S
authors.lastname: Raghavakaimal
authors.forename: Andre
authors.initials: A
authors.lastname: Terzic
authors.forename: Arshad
authors.initials: A
authors.lastname: Jahangir
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000375:Aging; D000818:Animals; D016922:Cellular Senescence; D020869:Gene Expression Profiling; D008928:Mitochondria / Q000378:metabolism*; D008954:Models, Biological; D009206:Myocardium / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D010085:Oxidative Phosphorylation; D006180:Proton-Translocating ATPases / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic
chemical_list: D000255:Adenosine Triphosphate; D006180:Proton-Translocating ATPases