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1 Department of Internal Medicine, Institute of Clinical Medicine, University of Tsukuba, Tsukuba, Japan
2 Department of Internal Medicine, Institute of Clinical Medicine, University of Tsukuba, Tsukuba, Japan; Center for Tsukuba Advanced Research Alliance, University of Tsukuba, Tsukuba, Japan
3 Institute of Health and Sport Sciences, University of Tsukuba, Tsukuba, Japan; Center for Tsukuba Advanced Research Alliance, University of Tsukuba, Tsukuba, Japan
4 Institute of Health and Sport Sciences, University of Tsukuba, Tsukuba, Japan
* To whom correspondence should be addressed. E-mail: t-miyauc{at}md.tsukuba.ac.jp.
Exercise training improves the aging-induced downregulation of myosin heavy chain (MHC) and sarcoplasmic reticulum Ca2+-ATPase (SR-Ca2+-ATPase), which participate in the regulation of cardiac contraction and relaxation. Thyroid hormone receptor (TR), a transcriptional activator, affected a regulation of gene expression of MHC and SR-Ca2+-ATPase. We hypothesized that myocardial TR signaling contributes to a molecular mechanism of exercise training-induced improvement of MHC and SR-Ca2+-ATPase genes
with cardiac function in old age. We investigated whether TR signaling and gene expression of MHC and SR-Ca2+-ATPase in the aged heart are affected by exercise training, using the hearts of sedentary young rats (4 months old), sedentary aged rats (23 months old), and trained aged rats (23 months old, swimming training for 8 weeks). 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-Ca2+-ATPase genes and the mRNA and protein expression of -MHC and SR-Ca2+-ATPase in the heart and plasma T3 and T4 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-Ca2+- ATPase genes, thereby contributing to the improvement of cardiac function in trained-aged hearts.
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