Aging-associated loss of skeletal muscle mass and force increases the risk of falls, impairs mobility, and leads to a reduced quality of life. High-intensity interval training (HIIT) is superior to moderate-intensity continuous training (MICT) for improving morphological and metabolic adaptations of skeletal muscle in older adults, but the underlying mechanism is unknown. Aged female rats underwent HIIT and MICT for 8 months, and their differential impacts on skeletal muscle proteome were investigated. HIIT resulted in a larger improvement in grip strength and fiber cross-sectional area, with similar increases in inclined plane performance and time to exhaustion. Proteomic analysis showed that common training adaptations of both protocols included changes to muscle contraction, focal adhesion signaling, mitochondrial function, apoptosis and regeneration, and anti-oxidation, whereas protein processing in the endoplasmic reticulum and adipocytokine signaling were specifically altered in the MICT and HIIT groups, respectively. Immunoblotting showed that upregulation of the adiponectin/AMPK signaling pathway may be associated with improvements in autophagy, oxidative stress, mitochondrial function, and apoptosis in aged skeletal muscle following HIIT. Thus, understanding the molecular differences in training adaptations from these two exercise modalities may aid in combatting sarcopenia.

The effects of high-intensity interval (HIIT) and moderate-intensity continuous training (MICT) on basal autophagy and mitochondrial function in cardiac and skeletal muscle and plasma metabolic phenotypes have not been clearly characterized. Here, we investigated how 10-weeks HIIT and MICT differentially modify basal autophagy and mitochondrial markers in cardiac and skeletal muscle and conducted an untargeted metabolomics study with proton nuclear magnetic resonance (¹H NMR) spectroscopy and multivariate statistical analysis of plasma metabolic phenotypes. Male Sprague–Dawley rats were separated into three groups: sedentary control (SED), MICT, and HIIT. Rats underwent evaluation of exercise performance, including exercise tolerance and grip strength, and blood lactate levels were measured immediately after an incremental exercise test. Plasma samples were analyzed by ¹H NMR. The expression of autophagy and mitochondrial markers and autophagic flux (LC3II/LC3-I ratio) in cardiac, rectus femoris, and soleus muscle were analyzed by western blotting. Time to exhaustion and grip strength increased significantly following HIIT compared with that in both SED and MICT groups. Compared with those in the SED group, blood lactate level, and the expression of SDH, COX-IV, and SIRT3 significantly increased in rectus femoris and soleus muscle of both HIIT and MICT groups. Meanwhile, SDH and COX-IV content of cardiac muscle and COX-IV and SIRT3 content of rectus femoris and soleus muscle increased significantly following HIIT compared with that following MICT. The expression of LC3-II, ATG-3, and Beclin-1 and LC3II/LC3-I ratio were significantly increased only in soleus and cardiac muscle following HIIT. These data indicate that HIIT was more effective for improving physical performance and facilitating cardiac and skeletal muscle adaptations that increase mitochondrial function and basal autophagic activities. Moreover, ¹H NMR spectroscopy and multivariate statistical analysis identified 11 metabolites in plasma, among which fine significantly and similarly changed after both HIIT and MICT, while BCAAs isoleucine, leucine, and valine and glutamine were changed only after HIIT. Together, these data indicate distinct differences in specific metabolites and autophagy and mitochondrial markers following HIIT vs. MICT and highlight the value of metabolomic analysis in providing more detailed insight into the metabolic adaptations to exercise training.