Effects of high-intensity interval training on mitochondrial supercomplex assembly and biogenesis, mitophagy, and the AMP-activated protein kinase pathway in the soleus muscle of aged female rats

Purpose: Exercise helps improve mitochondrial function to combat sarcopenia. Certain parts of the mitochondrial respiratory chain complex can form a higher-order structure called supercomplex to reduce the production of reactive oxygen species and improve muscle mass. The effect of exercise on the assembly of the mitochondrial supercomplex is still unclear. The aim of this study was to investigate the effects of long-term high-intensity interval training (HIIT) on mitochondrial biogenesis, mitophagy, and mitochondrial supercomplexes (mitoSCs) assembly in aging soleus muscle. Methods: Female Sprague-Dawley rats (n = 36) were randomly divided into four groups: young sedentary (Y-SED, 8 months old, n = 12), old sedentary (O-SED, 26 months old, n = 12), moderate-intensity continuous training (MICT, from 18 to 26 months old, n = 12), and HIIT (from 18 to 26 months old, n = 12). Rats in the MICT and HIIT groups were subjected to an 8-month training program. Real-time fluorescent quantitative polymerase chain reaction was used to measure the expression of the antioxidative factors, inflammatory factors, and mitochondrial fusion- and division-related genes. Western blotting was used to detect the expression of mitochondrial biogenesis and mitophagy markers and AMP-activated protein kinase (AMPK) pathway proteins. Enzyme-linked immunosorbent assays were used to determine serum irisin contents. Blue native polyacrylamide gel electrophoresis was used to assess the formation of mitochondrial supercomplexes. Results: Compared with the Y-SED group, the soleus muscle and mitochondria in the O-SED group showed reduced expression of mitophagy- and mitochondrial biogenesis-related proteins. In the HIIT group, the expression of autophagy-related proteins in the soleus muscle and mitochondria was significantly increased compared with that in the MICT group. Serum irisin and mitochondrial fusion protein levels significantly decreased with age. Superoxide dismutase 2 protein levels and AMPK pathway protein expression were significantly increased in the HIIT group compared with those in the other groups. Additionally, the expression levels of mitoSCs and the mRNA levels of interleukin-15 and optical atrophy 1 increased in the HIIT group compared with that in the MICT group. Conclusion: Compared with MICT, HIIT activated the AMPK pathway to upregulate mitochondrial biogenesis- and mitophagy-related proteins, and promote the assembly and formation of mitoSCs to improve the mitochondrial function of aging soleus muscles.

Automated summary

This study demonstrated that long-term high-intensity interval training (HIIT) could improve mitochondrial biogenesis, enhance mitochondrial function, and reduce reactive oxygen species in aging soleus muscle. Compared with moderate-intensity continuous training (MICT), HIIT activated the AMPK pathway to upregulate mitochondrial biogenesis- and mitophagy-related proteins, and promote the assembly and formation of mitoSCs, thereby improving muscle quality.