Aging-induced alterations in gene transcripts and functional activity of mitochondrial oxidative phosphorylation complexes in the heart

Claudia C. Preston, Andrew S. Oberlin, Ekhson L. Holmuhamedov, Anu Gupta, Sandeep Sagar, Rashad H.Khazi Syed, Sabeeh A. Siddiqui, Sreekumar Raghavakaimal, Andre Terzic, Arshad Jahangir

Research output: Contribution to journalArticle

83 Scopus citations

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 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 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.

Original languageEnglish (US)
Pages (from-to)304-312
Number of pages9
JournalMechanisms of Ageing and Development
Volume129
Issue number6
DOIs
StatePublished - Jun 1 2008

Keywords

  • ATP
  • Aging
  • Gene expression
  • Mitochondria
  • Myocardium
  • Oxidative phosphorylation
  • Transcription factors

ASJC Scopus subject areas

  • Aging
  • Developmental Biology

Fingerprint Dive into the research topics of 'Aging-induced alterations in gene transcripts and functional activity of mitochondrial oxidative phosphorylation complexes in the heart'. Together they form a unique fingerprint.

  • Cite this

    Preston, C. C., Oberlin, A. S., Holmuhamedov, E. L., Gupta, A., Sagar, S., Syed, R. H. K., Siddiqui, S. A., Raghavakaimal, S., Terzic, A., & Jahangir, A. (2008). Aging-induced alterations in gene transcripts and functional activity of mitochondrial oxidative phosphorylation complexes in the heart. Mechanisms of Ageing and Development, 129(6), 304-312. https://doi.org/10.1016/j.mad.2008.02.010