Electrical stimulation counteracts muscle decline in seniors

Helmut Kern, Laura Barberi, Stefan Löfler, Simona Sbardella, Samantha Burggraf, Hannah Fruhmann, Ugo Carraro, Simone Mosole, Nejc Sarabon, Michael Vogelauer, Winfried Mayr, Matthias Krenn, Jan Cvecka, Vanina Romanello, Laura Pietrangelo, Feliciano Protasi, Marco Sandri, Sandra Zampieri, Antonio Musaro, Helmut Kern, Laura Barberi, Stefan Löfler, Simona Sbardella, Samantha Burggraf, Hannah Fruhmann, Ugo Carraro, Simone Mosole, Nejc Sarabon, Michael Vogelauer, Winfried Mayr, Matthias Krenn, Jan Cvecka, Vanina Romanello, Laura Pietrangelo, Feliciano Protasi, Marco Sandri, Sandra Zampieri, Antonio Musaro

Abstract

The loss in muscle mass coupled with a decrease in specific force and shift in fiber composition are hallmarks of aging. Training and regular exercise attenuate the signs of sarcopenia. However, pathologic conditions limit the ability to perform physical exercise. We addressed whether electrical stimulation (ES) is an alternative intervention to improve muscle recovery and defined the molecular mechanism associated with improvement in muscle structure and function. We analyzed, at functional, structural, and molecular level, the effects of ES training on healthy seniors with normal life style, without routine sport activity. ES was able to improve muscle torque and functional performances of seniors and increased the size of fast muscle fibers. At molecular level, ES induced up-regulation of IGF-1 and modulation of MuRF-1, a muscle-specific atrophy-related gene. ES also induced up-regulation of relevant markers of differentiating satellite cells and of extracellular matrix remodeling, which might guarantee shape and mechanical forces of trained skeletal muscle as well as maintenance of satellite cell function, reducing fibrosis. Our data provide evidence that ES is a safe method to counteract muscle decline associated with aging.

Keywords: IGF-1; aging; electrical stimulation; extracellular matrix; microRNA; muscle atrophy; muscle performance; satellite cells.

Figures

Figure 1
Figure 1
Muscle morphology and fiber-type distribution. All muscle biopsies present well-packed myofibers, without signs of fibrosis, and inflammatory cell infiltration before (A) or after 9 weeks of training (B). The training induced an increase of either diameter and percentage of the fast-type fibers [brown stained (C,D)]. Bar 100 μm.
Figure 2
Figure 2
Electrical stimulation induces an increase of satellite cells. (A) Representative immunofluorescence analysis for N-CAM expression (red stained, arrowed). N-CAM expressing cells are increased in post-trained muscle compared with the pre-training condition. Nuclei are counterstained in blue with Hoechst. Bar 100 μm. (B) Representative co-immunofluorescence analyses of laminin (red staining) and Pax7 (green staining) expression in skeletal muscle biopsies comparing pre- to post-training conditions. The number of Pax7 positive cells (arrowed) is increased in biopsies of post-trained subjects, compared to the pre-training ones. Bar 100 μm. Right panel: percentage of Pax7+ cells in pre-trained and post-ES-trained muscles. Data are represented as average ± SD. ***p < 0.0001. (C) Real time PCR analysis for myogenin, miR-206, and miR-1 expression in pre-trained (PRE) and post-ES-trained (POST) muscles. Data are represented as average ± SEM. n = 16. *p < 0.05; **p < 0.005.
Figure 3
Figure 3
Expression analyses of genes controlling muscle mass and metabolism. Real time PCR analysis for the expression of IGF-1 isoforms (total IGF-1pan, IGF-1Ea, IGF-1Eb, IGF-1Ec) (A) Atrogin-1, MurF-1, Beclin1, p62 (B), Myostatin (C), PGC1α (D), and Nrf2 (E). Data are represented as average ± SEM. n = 16. **p < 0.005; ***p < 0.0005.
Figure 4
Figure 4
Electrical stimulation promotes ECM remodeling. Real time PCR analysis for Collagen I, Collagen III, Collagen VI, and miR-29. Data are represented as average ± SEM. n = 16. *p < 0.05; ***p < 0.0005.

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