Peroxisome proliferator-activated receptor (PPAR)-␣, a transcriptional activator, regulates genes of fatty acid (FA) metabolic enzymes. To study the contribution of PPAR-␣ to exercise training-induced improvement of FA metabolic capacity in the aged heart, we investigated whether PPAR-␣ signaling and expression of its target genes in the aged heart are affected by exercise training. We used hearts of sedentary young rat (4 mo old), sedentary aged rat (23 mo old), and swim-trained aged rat (23 mo old, training for 8 wk). The mRNA and protein expression of PPAR-␣ in the heart was significantly lower in the sedentary aged rats compared with the sedentary young rats and was significantly higher in the swim-trained aged rats compared with the sedentary aged rats. The activity of PPAR-␣ DNA binding to the transcriptional regulating region on the FA metabolic enzyme genes, the mRNA expression of 3-hydroxyacyl CoA dehydrogenase (HAD) and carnitine palmitoyl transferase-I, which are PPAR-␣ target genes, and the enzyme activity of HAD in the heart altered in association with changes of the myocardial PPAR-␣ mRNA and protein levels. These findings suggest that exercise training improves aging-induced downregulation in myocardial PPAR-␣-mediated molecular system, thereby contributing to the improvement of the FA metabolic enzyme activity in the trained-aged hearts.peroxisome proliferator-activated receptor-␣; swimming training; aged rat; fatty acid THE HEART is known for its ability to produce energy from fatty acids (FA) because of its important -oxidation equipment, but it can also derive energy from several other substrates, including glucose and lactate (10, 23). On a physiological condition, FA is considered to account for 60-70% of oxygen consumption for energy production in the heart (23). However, FA metabolic capacity in the heart is reduced by aging (19, 32).It has been reported that exercise training improved an aging-induced decrease of FA metabolic capacity in the heart (7, 18, 25, 32). However, the mechanisms for improving FA metabolic capacity in the heart by exercise training are unclear.Peroxisome proliferator-activated receptor (PPAR)-␣ is a member of the nuclear receptor transcription factor superfamily and is mainly expressed in the heart, liver, and kidney (2,13,29). The recent studies indicated that PPAR-␣ plays a critical role in the expression of genes involved in FA metabolism (13). PPAR-␣ heterodimerizes with the retinoid X receptor (RXR-␣) to bind to peroxisome proliferator-response elements (PPRE) in the upstream regions of a number of genes involved in metabolic homeostasis (13,29). PPAR-␣ regulates target genes encoding FA metabolic (-oxidation) enzymes and FA transporters such as FA binding protein, carnitine palmitoyl transferase-I (CPT-I), acyl-CoA synthase, 3-hydroxyacyl CoA dehydrogenase (HAD), apolipoproteins, and so on, suggesting that PPAR-␣ plays an important role in FA metabolic homeostasis (2,5,17,29). However, it is unknown whether the aging and subsequent exercise training affect...