title: Resveratrol enhanced FOXO3 phosphorylation via synergetic activation of SIRT1 and PI3K/Akt signaling to improve the effects of exercise in elderly rat hearts.
abstract: Exercise training is considered a benefit to heart function, but the benefit in aging hearts remains unknown. Activation of the PI3K-Akt survival pathway and suppression of Fas/FADD/caspase-8 apoptotic signaling by exercise training in hearts from young subjects have been described in our previous studies. However, the mechanisms are still unclear and need to be explored in aging hearts. Thus, 18-month-old rats were used as a model and underwent swimming exercise training, resveratrol treatment (15 mg/kg/day), or exercise training with resveratrol treatment for 1 month. The results showed that heart function in each group improved. However, the 18-month-old rats in the exercise-only group experienced the slightly inevitable impact of increased TNF-α, cell apoptosis, and fibrosis. In the protein analysis, the PI3K-Akt pathway was slightly increased with exercise training and resveratrol treatment, but Sirtuin 1 (SIRT1) was only highly activated with resveratrol treatment in the aged rat hearts. Moreover, the exercise training plus resveratrol group benefited from SIRT1 and PI3K-Akt dual pathways and blocked FOXO3 accumulation. Our experimental results strongly suggest that resveratrol treatment improves the beneficial effects of exercise training in aging rat hearts.
authors.affiliation: Department of Family Medicine, China Medical University Hospital, Taichung, Taiwan.
authors.forename: Chih-Hsueh
authors.initials: CH
authors.lastname: Lin
authors.forename: Cheng-Chieh
authors.initials: CC
authors.lastname: Lin
authors.forename: Wei-Jen
authors.initials: WJ
authors.lastname: Ting
authors.forename: Pei-Ying
authors.initials: PY
authors.lastname: Pai
authors.forename: Chia-Hua
authors.initials: CH
authors.lastname: Kuo
authors.forename: Tsung-Jung
authors.initials: TJ
authors.lastname: Ho
authors.forename: Wei-Wen
authors.initials: WW
authors.lastname: Kuo
authors.forename: Chung-Ho
authors.initials: CH
authors.lastname: Chang
authors.forename: Chih-Yang
authors.initials: CY
authors.lastname: Huang
authors.forename: Wan-Teng
authors.initials: WT
authors.lastname: Lin
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001706:Biopsy; D015153:Blotting, Western; D002352:Carrier Proteins / Q000378:metabolism*; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D020287:In Situ Nick-End Labeling; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D051058:Oncogene Protein v-akt / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D010805:Physical Conditioning, Animal / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077185:Resveratrol; D012264:Ribonucleotide Reductases / Q000037:antagonists & inhibitors; D015398:Signal Transduction / Q000187:drug effects; D056564:Sirtuin 1 / Q000378:metabolism*; D013267:Stilbenes / Q000494:pharmacology*
chemical_list: D020533:Angiogenesis Inhibitors; D002352:Carrier Proteins; C499515:FOXO3 protein, rat; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors; C574981:PI3KAP protein, rat; D013267:Stilbenes; D012264:Ribonucleotide Reductases; D051058:Oncogene Protein v-akt; C488368:Sirt1 protein, rat; D056564:Sirtuin 1; D000077185:Resveratrol