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. 2018 Jun 27;10(6):1356-1365.
doi: 10.18632/aging.101472.

Aged Cells in Human Skeletal Muscle After Resistance Exercise

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Free PMC article

Aged Cells in Human Skeletal Muscle After Resistance Exercise

Chi Yang et al. Aging (Albany NY). .
Free PMC article

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Abstract

It remains unclear how exercise, as an entropic event, brings benefit against human aging. Here we examined longitudinal changes of p16Ink4a+ senescent cells in skeletal muscle of young men (aged 22.5±1.7 y) before and after resistance exercise (0 h and 48 h) with multiple biopsies at two different protein availabilities: low protein (14%) and isocaloric high protein (44%) supplemented conditions. Immunohistochemistry analysis of muscle cross-sections using p16Ink4a and CD34 antibodies confirmed that the detected senescent cells were endothelial progenitor cells. Leukocyte infiltration into skeletal muscle increased during resistance exercise. The senescent cells in muscle decreased (-48%, P < 0.01) after exercise for 48 h. Low protein supplementation resulted in greater infiltrations of both CD68+ phagocytic macrophage and leukocyte, further decreased p16Ink4a+ senescent cells (-73%, P < 0.001), and delayed increases in regenerative CD163+ macrophage in skeletal muscle, compared with high protein supplemented condition. Significant gain in muscle mass after 12 weeks of training occurred only under high protein supplemented condition.

Conclusion: Rapid senescent cell clearance of human skeletal muscle during resistance exercise seems to associate with enhanced in situ phagocytosis. High protein availability accelerates resolution of muscle inflammation and promotes muscle increment after training.

Keywords: anti-aging; inflammation; macrophage; p16Ink4a; whey protein.

Conflict of interest statement

CONFLICTS OF INTEREST: There is no conflict of interest in any aspect of this study. We declare that the results of the study are presented clearly, honestly, and without fabrication, falsification, or inappropriate data manipulation.

Figures

Figure 1
Figure 1
Leukocyte infiltration in human skeletal muscle after resistance exercise. (A) Representative hematoxylin and eosin staining of a muscle cross-section (leukocytes infiltration indicated by an arrow). (B) Resistance exercise immediately increased leukocyte infiltration into skeletal muscle. High protein supplementation before and after resistance exercise attenuated exercise-induced leukocyte infiltration. * Significant difference against Baseline, P < 0.05; † Significant difference against Low Protein, P < 0.05. Low protein: 14% protein; High protein: 44% protein in weight.
Figure 2
Figure 2
Senescent endothelial progenitor cells (p16Ink4a+/CD34+) in human skeletal muscle after resistance exercise. (A) Representative immunohistochemical co-staining of muscle cross-sections (senescent cells indicated by arrows). Scale bar 550 mm. (B) Senescent endothelial progenitor cells decreased in human skeletal muscle after a single bout of resistance exercise, and to a greater extends under low protein supplemented condition. * Significant difference against Baseline, P < 0.05; † Significant difference against Low Protein, P < 0.05. Low protein: 14% protein; High protein: 44% protein in weight.
Figure 3
Figure 3
Phagocytic macrophage (CD68+) in human skeletal muscle after resistance exercise. (A) Representative immunohistochemical staining of a muscle cross-section (CD68+ macrophage indicated by an arrow). Scale bar 550 mm. (B) Low protein supplementation before and after resistance exercise enhanced CD68+ macrophage infiltration in skeletal muscle above High protein trial. * Significant difference against Baseline, P < 0.05; † Significant difference against Low Protein, P < 0.05. Low protein: 14% protein; High protein: 44% protein in weight.
Figure 4
Figure 4
Regenerative macrophage (CD163+) in human skeletal muscle after resistance exercise. (A) Representative immunohistochemical staining of a muscle cross-section (CD163+ macrophage indicated by an arrow). Scale bar 550 mm. (B) High protein supplementation before and after resistance exercise increased CD163+ macrophage presence in human skeletal muscle 48 h after exercise. * Significant difference against Baseline, P < 0.05; † Significant difference against Low Protein, P < 0.05. Low protein: 14% protein; High protein: 44% protein in weight.
Figure 5
Figure 5
Centrally nucleated fibers in human skeletal muscle after resistance exercise. (A) Representative hematoxylin and eosin staining of a muscle cross-section (centrally nucleated fibers indicated by arrows). Scale bar 550 mm. (B) (††) No difference between Low and High protein trials was found. * Significant difference against Baseline, P < 0.05. Low protein: 14% protein; High protein: 44% protein in weight.

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