Potent myofiber hypertrophy during resistance training in humans is associated with satellite cell-mediated myonuclear addition: a cluster analysis

A present debate in muscle biology is whether myonuclear addition is required during skeletal muscle hypertrophy. We utilized K-means cluster analysis to classify 66 humans after 16 wk of knee extensor resistance training as extreme (Xtr, n = 17), modest (Mod, n = 32), or nonresponders (Non, n = 17) based on myofiber hypertrophy, which averaged 58, 28, and 0%, respectively (Bamman MM, Petrella JK, Kim JS, Mayhew DL, Cross JM. J Appl Physiol 102: 2232–2239, 2007). We hypothesized that robust hypertrophy seen in Xtr was driven by superior satellite cell (SC) activation and myonuclear addition. Vastus lateralis biopsies were obtained at baseline and week 16. SCs were identified immunohistochemically by surface expression of neural cell adhesion molecule. At baseline, myofiber size did not differ among clusters; however, the SC population was greater in Xtr ( P < 0.01) than both Mod and Non, suggesting superior basal myogenic potential. SC number increased robustly during training in Xtr only (117%; P < 0.001). Myonuclear addition occurred in Mod (9%; P < 0.05) and was most effectively accomplished in Xtr (26%; P < 0.001). After training, Xtr had more myonuclei per fiber than Non (23%; P < 0.05) and tended to have more than Mod (19%; P = 0.056). Both Xtr and Mod expanded the myonuclear domain to meet (Mod) or exceed (Xtr) 2,000 μm2 per nucleus, possibly driving demand for myonuclear addition to support myofiber expansion. These findings strongly suggest myonuclear addition via SC recruitment may be required to achieve substantial myofiber hypertrophy in humans. Individuals with a greater basal presence of SCs demonstrated, with training, a remarkable ability to expand the SC pool, incorporate new nuclei, and achieve robust growth.

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Early-Phase Satellite Cell and Myonuclear Domain Adaptations to Slow-Speed vs. Traditional Resistance Training Programs

The Journal of Strength and Conditioning Research ◽

10.1519/jsc.0000000000000925 ◽

2015 ◽

Vol 29 (11) ◽

pp. 3105-3114 ◽

Cited By ~ 5

Author(s):

Jennifer R. Herman-Montemayor ◽

Robert S. Hikida ◽

Robert S. Staron

Keyword(s):

Resistance Training ◽

Satellite Cell ◽

Early Phase ◽

Training Programs ◽

Slow Speed ◽

Traditional Resistance Training ◽

Myonuclear Domain

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Acute and chronic resistance training downregulates select LINE-1 retrotransposon activity markers in human skeletal muscle

AJP Cell Physiology ◽

10.1152/ajpcell.00192.2017 ◽

2018 ◽

Vol 314 (3) ◽

pp. C379-C388 ◽

Cited By ~ 4

Author(s):

Matthew A. Romero ◽

C. Brooks Mobley ◽

Petey W. Mumford ◽

Paul A. Roberson ◽

Cody T. Haun ◽

...

Keyword(s):

Skeletal Muscle ◽

Resistance Training ◽

Resistance Exercise ◽

Satellite Cell ◽

Vastus Lateralis ◽

Future Research ◽

Resistance Training Program ◽

Myoblast Proliferation ◽

Retrotransposon Activity

Herein, we examined if acute or chronic resistance exercise affected markers of skeletal muscle long interspersed nuclear element-1 (LINE-1) retrotransposon activity. In study 1, 10 resistance-trained college-aged men performed three consecutive daily back squat sessions, and vastus lateralis biopsies were taken before (Pre), 2 h following session 1 (Post1), and 3 days following session 3 (Post2). In study 2, 13 untrained college-aged men performed a full-body resistance training program (3 days/wk), and vastus lateralis biopsies were taken before ( week 0) and ~72 h following training cessation ( week 12). In study 1, LINE-1 mRNA decreased 42–48% at Post1 and 2 ( P < 0.05), and reverse transcriptase (RT) activity trended downward at Post2 (−37%, P = 0.067). In study 2, LINE-1 mRNA trended downward at week 12 (−17%, P = 0.056) while LINE-1 promoter methylation increased (+142%, P = 0.041). Open reading frame (ORF)2p protein expression (−24%, P = 0.059) and RT activity (−26%, P = 0.063) also trended downward by week 12. Additionally, changes in RT activity versus satellite cell number were inversely associated ( r = −0.725, P = 0.008). Follow-up in vitro experiments demonstrated that 48-h treatments with lower doses (1 μM and 10 μM) of efavirenz and nevirapine (non-nucleoside RT inhibitors) increased myoblast proliferation ( P < 0.05). However, we observed a paradoxical decrease in myoblast proliferation with higher doses (50 μM) of efavirenz and delavirdine. This is the first report suggesting that resistance exercise downregulates markers of skeletal muscle LINE-1 activity. Given our discordant in vitro findings, future research is needed to thoroughly assess whether LINE-1-mediated RT activity enhances or blunts myoblast, or primary satellite cell, proliferative capacity.

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Lunges activate the gluteus maximus muscles more than back squats when both exercises are standardized

Isokinetics and Exercise Science ◽

10.3233/ies-210125 ◽

2021 ◽

pp. 1-7

Author(s):

Rodrigo Ramalho Aniceto ◽

André Luiz Torres Pirauá ◽

Leonardo da Silva Leandro ◽

Hélen Cristina Ferreira da Silva ◽

Diego Mesquita Silva ◽

...

Keyword(s):

Resistance Training ◽

Vastus Lateralis ◽

Knee Extensor ◽

Gluteus Maximus ◽

Biceps Femoris ◽

Lower Limbs ◽

Emg Activity ◽

Flexor Muscle ◽

Back Squat ◽

Trunk Inclination

BACKGROUND: Squats are considered one of the main exercises for the lower limbs and are used in resistance training under different contexts, including rehabilitation and sports performance. OBJECTIVE: To compare the EMG activity of different muscles in back squat and lunge exercises in trained women. METHODS: Ten healthy women experienced in resistance training performed back squat and lunge exercises on a Smith machine (total work: 70% of 1RM, 1 set, 10 repetitions and 2-s/2-s of execution speed) with an interval of 20-min between exercises. Both exercises were standardized in relation to the trunk inclination and were performed with an erect trunk parallel to the cursor of the guided bar. RESULTS: The EMG activity of the vastus medialis (VM), vastus lateralis (VL), biceps femoris (BF), and gluteus maximus (GM) were analyzed. There were no significant differences in the EMG activity of the VM, VL, and BF muscles between the back squat and lunge exercises (P> 0.05); however, GM activation was greater during the lunge exercise (effect size = 1.15; P= 0.001). CONCLUSIONS: Lunges were more effective in recruiting the GM when compared to back squats. However, both exercises can be recommended when the goal is knee extensor and flexor muscle activity.

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An 8-week resistance training protocol is effective in adapting quadriceps but not patellar tendon shear modulus measured by Supersonic Shearwave Imaging

10.1101/434423 ◽

2018 ◽

Author(s):

P. Mannarino ◽

T. T. Matta ◽

F. O. Oliveira

Keyword(s):

Mechanical Properties ◽

Resistance Training ◽

Shear Modulus ◽

Patellar Tendon ◽

Vastus Lateralis ◽

Knee Extensor ◽

Muscle Thickness ◽

Knee Extension ◽

Post Intervention ◽

Training Protocol

ABSTRACTHabitual loading and resistance training (RT) can determine changes in muscle and tendon morphology but also in its mechanical properties. Conventional ultrasound (US) evaluation of these mechanical properties present limitations that can now be overcome with the advent of Supersonic Shearwave Imaging (SSI). The objective of this study was to analyze the Vastus Lateralis (VL) and patellar tendon (PT) mechanical properties adaptations to an 8-week RT protocol using SSI. We submitted 15 untrained health young men to an 8-week RT directed knee extensor mechanism. VL and PT shear modulus (μ) was assessed pre and post intervention with SSI. VL muscle thickness (VL MT) and knee extension torque (KT) was also measure pre and post intervention to ensure the RT efficiency. Significant increases were observed in VL MT and KT (pre= 2.40 ± 0.40 cm and post= 2.63 ± 0.35 cm, p = 0.0111, and pre= 294.66 ± 73.98 Nm and post= 338.93 ± 76.39 Nm, p = 0.005, respectively). The 8-week RT was also effective in promoting VL μ adaptations (pre= 4.87 ± 1.38 kPa and post= 9.08.12 ± 1.86 kPa, p = 0.0105), but not in significantly affecting PT μ (pre= 78.85 ± 7.37 kPa and post= 66.41 ± 7.25 kPa, p = 0.1287). The present study showed that an 8-week resistance training protocol was effective in adapting VL μ but not PT μ. Further investigation should be conducted with special attention to longer interventions, to possible PT differential individual responsiviness and to the muscle-tendon resting state tension environment.

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Efficacy of myonuclear addition may explain differential myofiber growth among resistance-trained young and older men and women

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00190.2006 ◽

2006 ◽

Vol 291 (5) ◽

pp. E937-E946 ◽

Cited By ~ 217

Author(s):

John K. Petrella ◽

Jeong-su Kim ◽

James M. Cross ◽

David J. Kosek ◽

Marcas M. Bamman

Keyword(s):

Resistance Training ◽

Cell Activation ◽

Vastus Lateralis ◽

Knee Extensor ◽

Free Testosterone ◽

Sex Hormone Binding Globulin ◽

Muscle Stem Cells ◽

Igf I ◽

Paracrine Growth Factors ◽

Igf Binding

Skeletal muscle stem (satellite) cells supporting growth/regeneration are thought to be activated and incorporated into growing myofibers by both endocrine and locally expressed autocrine/paracrine growth factors, the latter being load sensitive. We recently found that myofiber hypertrophy with resistance training is superior in young men (YM) vs. young women and older adults (Kosek DJ, Kim JS, Petrella JK, Cross JM, and Bamman MM. J Appl Physiol 101: 531–544, 2006). We hypothesized that the advanced myofiber hypertrophy in YM is facilitated by myonuclear addition in response to a milieu promoting stem cell activation. Twenty-six young (27.0 ± 1 yr, 50% women) and 26 older (63.7 ± 1 yr, 50% women) adults completed 16 wk of knee extensor resistance training. Vastus lateralis biopsies were obtained at baseline, 24 h after one bout, and after 16 wk. Muscle stem cells were identified immunohistochemically with anti-neural cell adhesion molecule (NCAM+). Muscle transcript levels of IGF-I and mechanogrowth factor (MGF) were determined by RT-PCR. Serum IGF-I, IGF-binding protein (IGFBP)-3, IGFBP-1, total and free testosterone, sex hormone-binding globulin (SHBG), and androstenedione were assessed by radioimmunoassay. Myofiber hypertrophy was twofold greater in YM vs. others, and only YM increased NCAM+ cells per 100 myofibers (49%) and myonuclei per fiber (19%) ( P < 0.05). IGF-IEa mRNA was higher in young and increased acutely (29%) with summation by 16 wk (96%) ( P < 0.05). MGF mRNA increased only in young after one bout (81%) and by 16 wk (85%) ( P < 0.001). Circulating IGF-I was twofold higher in young, whereas IGFBP-1 was lowest in YM ( P < 0.05). Among men, free testosterone was 59% higher in YM ( P < 0.01). Myonuclear addition was most effectively accomplished in YM, which likely drove the superior growth.

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Influence of concentric and eccentric resistance training on architectural adaptation in human quadriceps muscles

Journal of Applied Physiology ◽

10.1152/japplphysiol.00578.2007 ◽

2007 ◽

Vol 103 (5) ◽

pp. 1565-1575 ◽

Cited By ~ 254

Author(s):

Anthony J. Blazevich ◽

Dale Cannavan ◽

David R. Coleman ◽

Sara Horne

Keyword(s):

Resistance Training ◽

Time Course ◽

Close Association ◽

Vastus Lateralis ◽

Knee Extensor ◽

Mechanical Stimuli ◽

Fascicle Length ◽

And Shifts ◽

Fascicle Angle ◽

Training And Detraining

Studies using animal models have been unable to determine the mechanical stimuli that most influence muscle architectural adaptation. We examined the influence of contraction mode on muscle architectural change in humans, while also describing the time course of its adaptation through training and detraining. Twenty-one men and women performed slow-speed (30°/s) concentric-only (Con) or eccentric-only (Ecc) isokinetic knee extensor training for 10 wk before completing a 3-mo detraining period. Fascicle length of the vastus lateralis (VL), measured by ultrasonography, increased similarly in both groups after 5 wk (ΔCon = +6.3 ± 3.0%, ΔEcc = +3.1 ± 1.6%, mean = +4.7 ± 1.7%; P < 0.05). No further increase was found at 10 wk, although a small increase (mean ∼2.5%; not significant) was evident after detraining. Fascicle angle increased in both groups at 5 wk (ΔCon = +11.1 ± 4.0%, ΔEcc = +11.9 ± 5.4%, mean = 11.5 ± 3.2%; P < 0.05) and 10 wk (ΔCon = +13.3 ± 3.0%, ΔEcc = +21.4 ± 6.9%, mean = 17.9 ± 3.7%; P < 0.01) in VL only and remained above baseline after detraining (mean = 13.2%); smaller changes in vastus medialis did not reach significance. The similar increase in fascicle length observed between the training groups mitigates against contraction mode being the predominant stimulus. Our data are also strongly indicative of 1) a close association between VL fascicle length and shifts in the torque-angle relationship through training and detraining and 2) changes in fascicle angle being driven by space constraints in the hypertrophying muscle. Thus muscle architectural adaptations occur rapidly in response to resistance training but are strongly influenced by factors other than contraction mode.

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Resistance training rejuvenates the mitochondrial methylome in aged human skeletal muscle

10.1101/2021.04.13.439651 ◽

2021 ◽

Author(s):

Bradley A. Ruple ◽

Joshua S. Godwin ◽

Paulo H.C. Mesquita ◽

Shelby C. Osburn ◽

Christopher G. Vann ◽

...

Keyword(s):

Skeletal Muscle ◽

Resistance Training ◽

Nuclear Dna ◽

Vastus Lateralis ◽

Knee Extensor ◽

Complex Iii ◽

Whole Body ◽

Cpg Sites ◽

Extensor Torque ◽

Older Males

Resistance training (RT) alters skeletal muscle nuclear DNA methylation patterns (or the methylome). However, no study has examined if RT affects the mitochondrial DNA (mtDNA) methylome. Herein, ten older untrained males (65+/-7 years old) performed six weeks of full-body RT (twice weekly). Body composition and knee extensor torque were assessed prior to and 72 hours following the last RT session. Vastus lateralis (VL) biopsies were also obtained. VL DNA was subjected to reduced representation bisulfite sequencing providing excellent coverage across the ~16-kilobase mtDNA methylome (254 CpG sites). Various biochemical assays were also performed, and older male data were compared to younger trained males (22+/-2 years old, n=7). RT increased whole-body lean tissue mass (p=0.017), VL thickness (p=0.012), and knee extensor torque (p=0.029) in older males. RT also profoundly affected the mtDNA methylome in older males, as 63% (159/254) of the CpG sites demonstrated reduced methylation (p<0.05). Notably, several mtDNA sites presented a more youthful signature after RT in older males when comparisons were made to younger males. The 1.12 kilobase D-loop/control region on mtDNA, which regulates mtDNA replication and transcription, possessed enriched hypomethylation in older males following RT. Enhanced expression of mitochondrial H- and L-strand genes and increases in mitochondrial complex III and IV protein levels were also observed (p<0.05). This is the first study to show RT alters the mtDNA methylome in skeletal muscle. Observed methylome alterations may enhance mitochondrial transcription, and RT remarkably evokes mitochondrial methylome profiles to mimic a more youthful signature in older males.

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