Transitioning to high-altitude environments is a big physiological challenge, and some degree of muscle atrophy is known to occur when transitioning to low-oxygen environments. One of the main potential reasons for this atrophy is hypoxia, resulting from the rarefaction of air and the reduced atmospheric pressure. Resistance training can be beneficial for counteracting muscle atrophy, but the mechanisms behind the interaction of resistance training and hypoxia and their influence on skeletal muscle have not yet been fully identified. A study in Scientific Reports demonstrates that microRNAs (miRNAs) may have an important regulatory role in muscle atrophy induced by high-altitude hypoxia and in the beneficial effect of resistance training.

First, the team established a rat model where hypoxia induces skeletal muscle atrophy and an appropriate four-week resistance training regimen that mitigated this muscle atrophy. Then, the researchers analyzed the expression profiles of miRNAs in the model. When comparing miRNA expression between the normal oxygen conditions and hypoxic condition groups, nine miRNAs were differently expressed and six of them downregulated in the hypoxic group. When comparing the hypoxia group with or without exercise, they observed that 14 miRNAs were differently expressed, with 13 of them being downregulated in the group with exercise. Further analysis identified around 8,000 potential target genes for the miRNAs affected by hypoxia. Similarly, 14,000 genes were identified as potential targets of miRNAs affected by resistance training in the context of hypoxia. Some of the miRNAs identified in hypoxic conditions have been previously linked to muscle fiber degeneration as they affect genes linked to diseases known to produce muscle atrophy, such as amyotrophic lateral sclerosis.

These results show that resistance training has potential for ameliorating hypoxia-induced skeletal muscle atrophy in rats, with miRNAs emerging as key regulators. The study identified several differentially expressed miRNAs that may have a regulatory role in both the progression of hypoxia-induced muscle atrophy and its amelioration through resistance training. Having more information on what is behind muscle atrophy and how resistance training produces this beneficial effect can help better target future therapies for diseases that produce muscle atrophy and better understand the role of oxygen availability in muscle integrity.

Original reference: Mei, T. et al. Sci. Rep. 14, 8388 (2024)