Exercise training improves cardiac function-related gene levels through thyroid hormone receptor signaling in aged rats

1 Cardiovascular Division, Department of Internal Medicine, Institute of Clinical Medicine, 2 Institute of Health and Sport Sciences, and 3 Center for Tsukuba Advanced Research Alliance, University of Tsukuba, Tsukuba, Ibaraki 305-0006, Japan Submitted 8 August 2003 ; accepted in final form 22 December 2003 Exercise training improves the aging-induced downregulation of myosin heavy chain (MHC) and sarcoplasmic reticulum (SR) Ca 2+ -ATPase, which participate in the regulation of cardiac contraction and relaxation. Thyroid hormone receptor (TR), a transcriptional activator, affected the regulation of gene expression of MHC and SR Ca 2+ -ATPase. We hypothesized that myocardial TR signaling contributes to a molecular mechanism of exercise training-induced improvement of MHC and SR Ca 2+ -ATPase genes with cardiac function in old age. We investigated whether TR signaling and gene expression of MHC and SR Ca 2+ -ATPase in the aged heart are affected by exercise training, using the hearts of sedentary young rats (4 mo old), sedentary aged rats (23 mo old), and trained aged rats (23 mo old, swimming training for 8 wk). Trained aged rats showed improvement in cardiac function. Expression of TR- 1 and TR- 1 proteins in the heart were significantly lower in sedentary aged rats than in sedentary young rats and were significantly higher in trained aged rats than in sedentary aged rats. The activity of TR DNA binding to the transcriptional regulatory region in the -MHC and SR Ca 2+ -ATPase genes and the mRNA and protein expression of -MHC and SR Ca 2+ -ATPase in the heart and plasma 3,3'-triiodothyronine and thyroxine levels were altered in association with changes in the myocardial TR protein levels. These findings suggest that exercise training improves the aging-induced downregulation of myocardial TR signaling-mediated transcription of MHC and SR Ca 2+ -ATPase genes, thereby contributing to the improvement of cardiac function in trained aged hearts. myosin heavy chain; sarcoplasmic reticulum Ca 2+ -ATPase; swimming training Address for reprint requests and other correspondence: T. Miyauchi, Cardiovascular Div., Dept. of Internal Medicine, Institute of Clinical Medicine, Univ. of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan (E-mail: t-miyauc{at}md.tsukuba.ac.jp ).