Aerobic exercise reduces sex differences in muscle function and inflammation in aged rats

This study tested whether late-life aerobic exercise influences sex differences in rats. We hypothesized that exercise, when started late in life, would reduce sex-differences in muscle function and inflammatory markers. Methods: 21-month-old male (n=11) and female (n=13) Fischer 344 rats were randomly assigned to sedentary (SED; 5M,7F) or exercise (EX; 6M,6F) groups. Trained animals ran at 60% maximal speed, 10° incline, 50 min/day, 5 days/week for 8 weeks. Exercise tolerance was assessed by maximal treadmill tests before and after training. At the end of the study, body composition was measured by echoMRI, in vivo muscle function by electrical stimulation, and blood, plantar flexor muscles, and spleen collected. Blood samples were analyzed for total white blood cells, relative immune cell composition, and tumor necrosis factor-alpha (TNF-α). Differences between groups were analyzed using two-way ANOVAs, followed by a Tukey’s post hoc test when appropriate, and Pearson’s correlations. Statistical significance was set at p < 0.05. Results: There was a significant effect of exercise (p < 0.0001) on body composition, with no significant effects of sex or exercise x sex interaction. Exercise tolerance was influenced by both sex (p < 0.001) and exercise (p < 0.001), with higher exercise tolerance in females and trained rats. We observed a significant exercise x sex interaction for skeletal muscle function, measured as maximal torque at 120 Hz. Specifically, maximal torque was higher in female SED than in male SED, and lower in male SED compared to male EX (p < 0.05). Both plantar flexors and spleen mass, normalized to body mass, showed a significant effect of sex. Males had a significantly larger spleen (p = 0.001), and females had greater skeletal muscle mass (p = 0.001). Since spleen enlargement reflects systemic inflammation, which can suppress muscle growth, we measured inflammatory markers. Plasma TNF-α levels were significantly higher in males than in females (p < 0.001). Total white blood cell counts showed a significant effect of sex, with males exhibiting higher counts (p = 0.004). The relative abundance of immune cell types was similar across sexes and training status, except for monocytes, which displayed a significant exercise x sex interaction (p = 0.001): male SED had higher percentages than female SED, and exercise appeared to normalize this difference. Relative monocytes were negatively correlated with both skeletal muscle mass (r = -0.70, p = 0.0004) and muscle torque (r = -0.55, p = 0.011). Conclusions: Our data show that aged male rats had larger spleen, higher TNF-α and white blood cell counts, and elevated monocyte percentages compared to females. Inflammatory markers were negatively associated with skeletal muscle mass and function. Late-life aerobic exercise improved skeletal muscle function, exercise tolerance, and immune profile, and appeared to mitigate sex differences in aged rats. This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.