Short-Duration Swimming Exercise after Myocardial Infarction Attenuates Cardiac Dysfunction and Regulates Mitochondrial Quality Control in Aged Mice

Abstract

Background Exercise benefits to cardiac rehabilitation (CR) following stable myocardial infarction (MI). The suitable exercise duration for aged patients with coronary heart disease (CHD) remains controversial, and the underlying molecular mechanism is still unclear. Methods and Results 18-Month-old mice after stable MI were randomly submitted to different durations of exercise, including 15 and 60 min swimming training (ST) once per day, five times a week for 8 weeks. Compared to sedentary mice, 15 min ST, rather than 60 min ST, significantly augmented left ventricular function, increased survival rate, and suppressed myocardial fibrosis and apoptosis. 15 min ST improved mitochondrial morphology via regulating mitochondrial fission-fusion signaling. 15 min ST regulated mitophagy signaling via inhibiting LC3-II and P62 levels and increasing PINK/Parkin expression. 15 min ST also inhibited ROS production and enhanced antioxidant SOD2 activity. Notably, 15 min ST significantly increased sirtuin (SIRT) 3 level (2.7-fold) in vivo while the inhibition of SIRT3 exacerbated senescent H9c2 cellular LDH release and ROS production under hypoxia. In addition, SIRT3 silencing impairs mitochondrial dynamics and mitophagy in senescent cardiomyocytes against simulated ischemia (SI) injury. Conclusion Collectively, our study demonstrated for the first time that sustained short-duration exercise, rather than long-duration exercise, attenuates cardiac dysfunction after MI in aged mice. It is likely that the positive regulation induced by a short-duration ST regimen on the elevated SIRT3 protein level improved mitochondrial quality control and decreased apoptosis and fibrosis contributed to the observed more resistant phenotype.

Protein and Mitochondria Quality Control Mechanisms and Cardiac Aging

“…Likewise, exercise training induced changes in autophagic function and fatty acid utilization in rabbit hearts following MI [175]. When 18 month-old mice challenged with left coronary artery ligation-induced MI were subjected to 15 min bouts of swimming, five times per week, for 8 weeks, survival rate and left ventricular function were significantly improved and myocardial fibrosis and apoptosis were reduced, when compared to age-matched mice that were sedentary [176]. While these studies clearly suggest that consistent dynamic physical exercise may improve indexes of autophagy and mitophagy in the context of aging, further in-depth mechanistic investigations are required.…”

Central and Peripheral Metabolic Defects Contribute to the Pathogenesis of Alzheimer's Disease: Targeting Mitochondria for Diagnosis and Prevention

“…Exercise also improves electron transport chain function by increasing complex I activity and improves mitochondrial dynamics by upregulating Drp1 levels (142). Swim training regulates mitochondrial quality control by inhibiting LC-3b turnover-mediated autophagy and PINK1/Parkin-mediated mitophagy in aged mice (465). Regular maternal exercise during pregnancy has long-lasting effects on metabolic programming in the brains of offspring and increases BDNF levels, specifically in mitochondrial function as indicated by increased mitochondrial membrane potential and mass, activates a-ketoglutarate dehydrogenase and complex IV, and enhances Mfn1 and Drp1 levels, which then protect against Ab-induced neurotoxicity and the cognitive impairment of the offspring in their lifetime (202).…”

Long‐term exercise prevents hepatic steatosis: a novel role of FABP1 in regulation of autophagy‐lysosomal machinery

“…The water temperature was maintained 30 6 1°C. The exercise protocol was modified from our previously published procedure (18)(19)(20)(21)(22). The SE protocol consisted of 12 wk of training.…”