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Voluntary wheel running attenuates peptidoglycan-polysaccharide-induced inflammation and preserves skeletal muscle remodeling in male C57BL/6J mice

1 May 2026

Kinoshita R, Yamaguchi T, Ato S, Kouzaki K, Tamura Y, Nakazato K.

Summary

What the study found

This study demonstrates that regular physical activity can protect muscle tissue from the damaging effects of chronic systemic inflammation. Researchers found that exercise lowers markers of inflammation in the blood and allows muscles to maintain their size and health even during an active inflammatory response.

Key findings

  • Exercise significantly attenuated systemic inflammation by lowering levels of pro-inflammatory cytokines like tumor necrosis factor-α and interleukin-1β.
  • Physical activity prevented muscle fiber atrophy, preserving the size and weight of muscles that usually shrink under inflammatory conditions.
  • Running decreased markers of oxidative stress in the muscles, specifically reducing levels of 4-hydroxynonenal.
  • Voluntary movement enhanced muscle protein turnover by increasing the production of new proteins and reducing the breakdown of existing ones.

Practical takeaways

For those focused on longevity, consistent aerobic exercise is a critical tool for counteracting "inflammaging," the age-related increase in systemic inflammation that degrades muscle quality. Maintaining an active lifestyle ensures that the body can still repair and build muscle effectively, even when facing underlying inflammatory stressors.

Limitations

Because this research was performed on male C57BL/6J mice, the findings may not be identical in humans or reflect the biological differences present in females. The study also focused on a specific bacterial-induced model of inflammation rather than the complex, multifaceted causes of human chronic disease.

Abstract

Chronic systemic inflammation (CSI) is associated with skeletal muscle dysfunction and may impair adaptive responses. This study investigated whether skeletal muscle responses to voluntary wheel running (VWR) are maintained following exposure to CSI. Twelve-week-old male C57BL/6J mice were assigned to Saline+Sedentary, Peptidoglycan-Polysaccharide (PG-PS) + Sedentary, Saline+Exercise, and PG-PS + Exercise groups (n = 12 per group), with PG-PS used to induce CSI. Following 3 weeks of intervention, blood and lower-leg skeletal muscles were collected. Total running distance did not differ between exercise groups. PG-PS administration increased serum tumor necrosis factor-α and interleukin-1β levels in sedentary mice, whereas these levels were attenuated in VWR mice. Under sedentary conditions, soleus muscle weight and fiber cross-sectional area (CSA) were lower in PG-PS-treated mice. Exercise was associated with higher soleus muscle mass and fiber CSA in both saline- and PG-PS-treated mice. PG-PS increased 4-hydroxynonenal levels in the soleus muscle, whereas VWR was associated with lower levels. VWR markedly increased muscle protein synthesis and reduced markers of muscle protein breakdown, indicating enhanced protein turnover independent of PG-PS treatment. These findings suggest that exercise-induced increases in muscle mass and fiber size occur independent of PG-PS treatment. Clinically, whole-body exercise may represent a physiologically relevant, non-pharmacological strategy to support skeletal muscle health under chronic inflammatory conditions.
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