The effects of resistance training on denervated myofibers, senescent cells, and associated protein markers in middle-aged adults

Ruple, B.; Mattingly, M.; Godwin, J.; McIntosh, M.; Kontos, N.; Agyin-Birikorang, A.; Michel, J. M.; Plotkin, D.; Chen, S.-Y.; Ziegenfuss, T.; Fruge, A.; Gladden, L. B.; Robinson, A.; Mobley, C. B.; Mackey, A. L.; Roberts, M.

doi:10.1101/2023.10.04.560958

bioRxiv · 10.1101/2023.10.04.560958

The effects of resistance training on denervated myofibers, senescent cells, and associated protein markers in middle-aged adults

Ruple, B.·Mattingly, M.·Godwin, J.·McIntosh, M.·Kontos, N.·Agyin-Birikorang, A.·Michel, J. M.·Plotkin, D.·Chen, S.-Y.·Ziegenfuss, T.·Fruge, A.·Gladden, L. B.·Robinson, A.·Mobley, C. B.·Mackey, A. L.·Roberts, M.

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Abstract

Denervated myofibers and senescent cells are hallmarks of skeletal muscle aging. However, sparse research has examined how resistance training affects these outcomes. We investigated the effects of unilateral leg extensor resistance training on denervated myofibers, senescent cells, and associated protein markers in middle-aged participants (MA, 55{+/-}8 years old, 17 females, 9 males). We obtained vastus lateralis (VL) muscle cross-sectional area (mCSA), VL biopsies, and strength assessments before and after training. Fiber cross-sectional area (fCSA), satellite cells (Pax7+), denervated myofibers (NCAM+), senescent cells (p16+ or p21+), senescence-related proteins, and senescence-associated secretory phenotype (SASP) proteins were analyzed from biopsied muscle. Leg extensor peak torque increased after training (p<0.001), while VL mCSA trended upward (p=0.082). No significant changes were observed for fCSA, NCAM+ myofibers, or senescent (p16+ or p21+) cells, albeit satellite cells increased after training (p=0.037). While >90% satellite cells were not p16+ or p21+, most p16+ and p21+ cells were Pax7+ (>90% on average). Training altered 13/46 proteins related to muscle-nerve communication (all upregulated, p<0.05) and 10/19 proteins related to cellular senescence (9 upregulated, p<0.05). Only 1/17 SASP proteins increased with training (IGFBP-3, p=0.031). In conclusion, resistance training upregulates proteins associated with muscle-nerve communication in MA participants but does not alter NCAM+ myofibers. Moreover, while training increases senescence-related proteins in skeletal muscle, this coincided with an increase in satellite cells but not alterations in senescent cell content or SASP proteins. Hence, we interpret these collective findings as resistance training being an unlikely inducer of cellular senescence in humans.

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Ruple, B., Mattingly, M., Godwin, J., McIntosh, M., Kontos, N., Agyin-Birikorang, A., Michel, J. M., Plotkin, D., Chen, S.-Y., Ziegenfuss, T., Fruge, A., Gladden, L. B., Robinson, A., Mobley, C. B., Mackey, A. L., Roberts, M.. 2023-10-06. The effects of resistance training on denervated myofibers, senescent cells, and associated protein markers in middle-aged adults. https://doi.org/10.1101/2023.10.04.560958

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