Control of mitochondrial gene expression in the aging rat myocardium.
Aging induces complex changes in myocardium bioenergetic and contractile properties. Using F344BNF(1) rats, we examined age-dependent changes in myocardial bioenergetic enzymes (catalytic activities and transcript levels) and mRNA levels of putative transcriptional regulators of bioenergetic genes. Very old rats (35 months) showed a 22% increase in ventricular mass with no changes in DNA or RNA per gram. Age-dependent cardiac hypertrophy was accompanied by complex changes in mitochondrial enzymes. Enzymes of the Krebs cycle and electron transport system remained within 15% of the values measured in adult heart, significant decreases occurring in citrate synthase (10%) and aconitase (15%). Transcripts for these enzymes were largely unaffected by aging, although mRNA levels of putative transcriptional regulators of the enzymes (nuclear respiratory factor (NRF) 1 and 2 alpha subunit) increased by about 30%-50%. In contrast, enzymes of fatty acid oxidation exhibited a more diverse pattern, with a 50% decrease in beta-hydroxyacyl-CoA dehydrogenase (HOAD) and no change in long-chain acyl-CoA dehydrogenase or carnitine palmitoyltransferase. Transcript levels for fatty acid oxidizing enzymes covaried with HOAD, which declined significantly by 30%. There were no significant changes in the relative transcript levels of regulators of genes for fatty acid oxidizing enzymes: peroxisome proliferator-activated receptor-alpha (PPARalpha), PPARbeta, or PPARgamma coactivator-1alpha (PGC-1alpha). There were no changes in the mRNA levels of Sirt1, a histone-modifying enzyme that interacts with PGC-1alpha. Collectively, these data suggest that aging causes complex changes in the enzymes of myocardial energy metabolism, triggered in part by NRF-independent pathways as well as post-transcriptional regulation.
LeMoine
Christophe M R
CM
Department of Biology, Queen's University, Kingston, Canada.
McClelland
Grant B
GB
Lyons
Carrie N
CN
Mathieu-Costello
Odile
O
Moyes
Christopher D
CD
D000375:Aging / Q000235:genetics*; D000818:Animals; D001483:Base Sequence; D050260:Carbohydrate Metabolism; D017931:DNA Primers / Q000235:genetics; D005227:Fatty Acids / Q000378:metabolism; D008297:Male; D008929:Mitochondria, Heart / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism*; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism*; D051264:Nuclear Respiratory Factors / Q000235:genetics / Q000378:metabolism; D047492:Peroxisome Proliferator-Activated Receptors / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011914:Rats, Inbred BN; D011916:Rats, Inbred F344; D056564:Sirtuin 1; D037761:Sirtuins / Q000235:genetics / Q000378:metabolism
D017931:DNA Primers; D005227:Fatty Acids; D051264:Nuclear Respiratory Factors; D047492:Peroxisome Proliferator-Activated Receptors; D012333:RNA, Messenger; C447939:SIRT1 protein, human; D056564:Sirtuin 1; D037761:Sirtuins