Effect of aging on mitochondrial energetics in the human atria


Center for Integrative Research on Cardiovascular Aging, Aurora St. Luke's Medical Center, Aurora Cardiovascular Services, Aurora Sinai/Aurora St. Luke's Medical Centers


Energy production in myocardial cells occurs mainly in the mitochondrion. Although alterations in mitochondrial functions in the senescent heart have been documented, the molecular bases for the aging-associated decline in energy metabolism in the human heart are not fully understood. In this study, we examined transcription profiles of genes coding for mitochondrial proteins in atrial tissue from aged (≥65 years old) and comorbidities-matched adult (old) patients with preserved left ventricular function. We also correlated changes in functional activity of mitochondrial oxidative phosphorylation (OXPHOS) complexes with gene expression changes. There was significant alteration in the expression of 10% (101/1,008) of genes coding for mitochondrial proteins, with 86% downregulated (87/101). Forty-nine percent of the altered genes were confined to mitochondrial energetic pathways. These changes were associated with a significant decrease in respiratory capacity of mitochondria oxidizing glutamate and malate and functional activity of complex I activity that correlated with the downregulation of NDUFA6, NDUFA9, NDUFB5, NDUFB8, and NDUFS2 genes coding for NADH dehydrogenase subunits. Thus, aging is associated with a decline in activity of OXPHOS within the broader transcriptional downregulation of genes regulating mitochondrial energetics, providing a substrate for reduced energetic efficiency in the senescent human atria.

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