Browsing by Author "Young, Kaelin C"
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Item Open Access Acute and chronic effects of resistance training on skeletal muscle markers of mitochondrial remodeling in older adults(Physiological Reports, 2020-08) Mesquita, Paulo HC; Lamb, Donald A; Parry, Hailey A; Moore, Johnathon H; Smith, Morgan A; Vann, Christopher G; Osburn, Shelby C; Fox, Carlton D; Ruple, Bradley A; Huggins, Kevin W; Fruge, Andrew D; Young, Kaelin C; Kavazis, Andreas N; Roberts, Michael DItem Open Access An intron variant of the GLI family zinc finger 3 (GLI3) gene differentiates resistance training-induced muscle fiber hypertrophy in younger men.(FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2021-05) Vann, Christopher G; Morton, Robert W; Mobley, Christopher B; Vechetti, Ivan J; Ferguson, Brian K; Haun, Cody T; Osburn, Shelby C; Sexton, Casey L; Fox, Carlton D; Romero, Matthew A; Roberson, Paul A; Oikawa, Sara Y; McGlory, Chris; Young, Kaelin C; McCarthy, John J; Phillips, Stuart M; Roberts, Michael DWe examined the association between genotype and resistance training-induced changes (12 wk) in dual x-ray energy absorptiometry (DXA)-derived lean soft tissue mass (LSTM) as well as muscle fiber cross-sectional area (fCSA; vastus lateralis; n = 109; age = 22 ± 2 y, BMI = 24.7 ± 3.1 kg/m2 ). Over 315 000 genetic polymorphisms were interrogated from muscle using DNA microarrays. First, a targeted investigation was performed where single nucleotide polymorphisms (SNP) identified from a systematic literature review were related to changes in LSTM and fCSA. Next, genome-wide association (GWA) studies were performed to reveal associations between novel SNP targets with pre- to post-training change scores in mean fCSA and LSTM. Our targeted investigation revealed no genotype-by-time interactions for 12 common polymorphisms regarding the change in mean fCSA or change in LSTM. Our first GWA study indicated no SNP were associated with the change in LSTM. However, the second GWA study indicated two SNP exceeded the significance level with the change in mean fCSA (P = 6.9 × 10-7 for rs4675569, 1.7 × 10-6 for rs10263647). While the former target is not annotated (chr2:205936846 (GRCh38.p12)), the latter target (chr7:41971865 (GRCh38.p12)) is an intron variant of the GLI Family Zinc Finger 3 (GLI3) gene. Follow-up analyses indicated fCSA increases were greater in the T/C and C/C GLI3 genotypes than the T/T GLI3 genotype (P < .05). Data from the Auburn cohort also revealed participants with the T/C and C/C genotypes exhibited increases in satellite cell number with training (P < .05), whereas T/T participants did not. Additionally, those with the T/C and C/C genotypes achieved myonuclear addition in response to training (P < .05), whereas the T/T participants did not. In summary, this is the first GWA study to examine how polymorphisms associate with the change in hypertrophy measures following resistance training. Future studies are needed to determine if the GLI3 variant differentiates hypertrophic responses to resistance training given the potential link between this gene and satellite cell physiology.Item Open Access Biomarkers associated with low, moderate, and high vastus lateralis muscle hypertrophy following 12 weeks of resistance training(PLOS ONE) Mobley, Christopher B; Haun, Cody T; Roberson, Paul A; Mumford, Petey W; Kephart, Wesley C; Romero, Matthew A; Osburn, Shelby C; Vann, Christopher G; Young, Kaelin C; Beck, Darren T; Martin, Jeffrey S; Lockwood, Christopher M; Roberts, Michael DItem Open Access Effects of Graded Whey Supplementation During Extreme-Volume Resistance Training(Frontiers in Nutrition) Haun, Cody T; Vann, Christopher G; Mobley, Christopher B; Roberson, Paul A; Osburn, Shelby C; Holmes, Hudson M; Mumford, Petey M; Romero, Matthew A; Young, Kaelin C; Moon, Jordan R; Gladden, L Bruce; Arnold, Robert D; Israetel, Michael A; Kirby, Annie N; Roberts, Michael DItem Open Access Effects of High-Volume Versus High-Load Resistance Training on Skeletal Muscle Growth and Molecular Adaptations.(Frontiers in physiology, 2022-01) Vann, Christopher G; Sexton, Casey L; Osburn, Shelby C; Smith, Morgan A; Haun, Cody T; Rumbley, Melissa N; Mumford, Petey W; Montgomery, Nathan T; Ruple, Bradley A; McKendry, James; Mcleod, Jonathan; Bashir, Adil; Beyers, Ronald J; Brook, Matthew S; Smith, Kenneth; Atherton, Philip J; Beck, Darren T; McDonald, James R; Young, Kaelin C; Phillips, Stuart M; Roberts, Michael DWe evaluated the effects of higher-load (HL) versus (lower-load) higher-volume (HV) resistance training on skeletal muscle hypertrophy, strength, and muscle-level molecular adaptations. Trained men (n = 15, age: 23 ± 3 years; training experience: 7 ± 3 years) performed unilateral lower-body training for 6 weeks (3× weekly), where single legs were randomly assigned to HV and HL paradigms. Vastus lateralis (VL) biopsies were obtained prior to study initiation (PRE) as well as 3 days (POST) and 10 days following the last training bout (POSTPR). Body composition and strength tests were performed at each testing session, and biochemical assays were performed on muscle tissue after study completion. Two-way within-subject repeated measures ANOVAs were performed on most dependent variables, and tracer data were compared using dependent samples t-tests. A significant interaction existed for VL muscle cross-sectional area (assessed via magnetic resonance imaging; interaction p = 0.046), where HV increased this metric from PRE to POST (+3.2%, p = 0.018) whereas HL training did not (-0.1%, p = 0.475). Additionally, HL increased leg extensor strength more so than HV training (interaction p = 0.032; HV < HL at POST and POSTPR, p < 0.025 for each). Six-week integrated non-myofibrillar protein synthesis (iNon-MyoPS) rates were also higher in the HV versus HL condition, while no difference between conditions existed for iMyoPS rates. No interactions existed for other strength, VL morphology variables, or the relative abundances of major muscle proteins. Compared to HL training, 6 weeks of HV training in previously trained men optimizes VL hypertrophy in lieu of enhanced iNon-MyoPS rates, and this warrants future research.Item Open Access Effects of Resistance Training on the Redox Status of Skeletal Muscle in Older Adults(Antioxidants) Mesquita, Paulo HC; Lamb, Donald A; Godwin, Joshua S; Osburn, Shelby C; Ruple, Bradley A; Moore, Johnathon H; Vann, Christopher G; Huggins, Kevin W; Fruge, Andrew D; Young, Kaelin C; Kavazis, Andreas N; Roberts, Michael DThe aim of this study was to investigate the effects of resistance training (RT) on the redox status of skeletal muscle in older adults. Thirteen males aged 64 ± 9 years performed full-body RT 2x/week for 6 weeks. Muscle biopsies were obtained from the vastus lateralis prior to and following RT. The mRNA, protein, and enzymatic activity levels of various endogenous antioxidants were determined. In addition, skeletal muscle 4-hydroxynonenal and protein carbonyls were determined as markers of oxidative damage. Protein levels of heat shock proteins (HSPs) were also quantified. RT increased mRNA levels of all assayed antioxidant genes, albeit protein levels either did not change or decreased. RT increased total antioxidant capacity, catalase, and glutathione reductase activities, and decreased glutathione peroxidase activity. Lipid peroxidation also decreased and HSP60 protein increased following RT. In summary, 6 weeks of RT decreased oxidative damage and increased antioxidant enzyme activities. Our results suggest the older adult responses to RT involve multi-level (transcriptional, post-transcriptional, and post-translational) control of the redox status of skeletal muscle.Item Open Access Molecular Differences in Skeletal Muscle After 1 Week of Active vs. Passive Recovery From High-Volume Resistance Training(Journal of Strength and Conditioning Research, 2021-08) Vann, Christopher G; Haun, Cody T; Osburn, Shelby C; Romero, Matthew A; Roberson, Paul A; Mumford, Petey W; Mobley, C Brooks; Holmes, Hudson M; Fox, Carlton D; Young, Kaelin C; Roberts, Michael DAbstract Vann, CG, Haun, CT, Osburn, SC, Romero, MA, Roberson, PA, Mumford, PW, Mobley, CB, Holmes, HM, Fox, CD, Young, KC, and Roberts, MD. Molecular differences in skeletal muscle after 1 week of active vs. passive recovery from high-volume resistance training. J Strength Cond Res 35(8): 2102–2113, 2021—Numerous studies have evaluated how deloading after resistance training (RT) affects strength and power outcomes. However, the molecular adaptations that occur after deload periods remain understudied. Trained, college-aged men (n = 30) performed 6 weeks of whole-body RT starting at 10 sets of 10 repetitions per exercise per week and finishing at 32 sets of 10 repetitions per exercise per week. After this period, subjects performed either active (AR; n = 16) or passive recovery (PR; n = 14) for 1 week where AR completed ∼15% of the week 6 training volume and PR ceased training. Variables related to body composition and recovery examined before RT (PRE), after 6 weeks of RT (POST), and after the 1-week recovery period (DL). Vastus lateralis (VL) muscle biopsies and blood samples were collected at each timepoint, and various biochemical and histological assays were performed. Group × time interactions (p < 0.05) existed for skeletal muscle myosin heavy chain (MHC)-IIa mRNA (AR > PR at POST and DL) and 20S proteasome activity (post-hoc tests revealed no significance in groups over time). Time effects (P < 0.05) existed for total mood disturbance and serum creatine kinase and mechano growth factor mRNA (POST > PRE &D L), VL pressure to pain threshold and MHC-IIx mRNA (PRE&DL > POST), Atrogin-1 and MuRF-1 mRNA (PRE < POST < DL), MHC-I mRNA (PRE < POST & DL), myostatin mRNA (PRE & POST < DL), and mechanistic target of rapamycin (PRE > POST & DL). No interactions or time effects were observed for barbell squat velocity, various hormones, histological metrics, polyubiquitinated proteins, or phosphorylated/pan protein levels of 4E-BP1, p70S6k, and AMPK. One week of AR after a high-volume training block instigates marginal molecular differences in skeletal muscle relative to PR. From a practical standpoint, however, both paradigms elicited largely similar responses.Item Open Access Muscle fiber hypertrophy in response to 6 weeks of high-volume resistance training in trained young men is largely attributed to sarcoplasmic hypertrophy(PLOS ONE) Haun, Cody T; Vann, Christopher G; Osburn, Shelby C; Mumford, Petey W; Roberson, Paul A; Romero, Matthew A; Fox, Carlton D; Johnson, Christopher A; Parry, Hailey A; Kavazis, Andreas N; Moon, Jordan R; Badisa, Veera LD; Mwashote, Benjamin M; Ibeanusi, Victor; Young, Kaelin C; Roberts, Michael DItem Open Access Muscle phenotype is related to motor unit behavior of the vastus lateralis during maximal isometric contractions(Physiological Reports, 2018-03) Colquhoun, Ryan J; Magrini, Mitchel A; Haun, Cody T; Muddle, Tyler WD; Tomko, Patrick M; Luera, Micheal J; Mackey, Cameron S; Vann, Christopher G; Martin, Jeffrey S; Young, Kaelin C; DeFreitas, Jason M; Roberts, Michael D; Jenkins, Nathaniel DMItem Open Access Pre-training Skeletal Muscle Fiber Size and Predominant Fiber Type Best Predict Hypertrophic Responses to 6 Weeks of Resistance Training in Previously Trained Young Men(Frontiers in Physiology) Haun, Cody T; Vann, Christopher G; Mobley, C Brooks; Osburn, Shelby C; Mumford, Petey W; Roberson, Paul A; Romero, Matthew A; Fox, Carlton D; Parry, Hailey A; Kavazis, Andreas N; Moon, Jordan R; Young, Kaelin C; Roberts, Michael DItem Open Access Resistance training increases muscle NAD+ and NADH concentrations as well as NAMPT protein levels and global sirtuin activity in middle-aged, overweight, untrained individuals(Aging, 2020-05-05) Lamb, Donald A; Moore, Johnathon H; Mesquita, Paulo Henrique Caldeira; Smith, Morgan A; Vann, Christopher G; Osburn, Shelby C; Fox, Carlton D; Lopez, Hector L; Ziegenfuss, Tim N; Huggins, Kevin W; Goodlett, Michael D; Fruge, Andrew D; Kavazis, Andreas N; Young, Kaelin C; Roberts, Michael DItem Open Access Resistance training rejuvenates the mitochondrial methylome in aged human skeletal muscle(The FASEB Journal, 2021-09) Ruple, Bradley A; Godwin, Joshua S; Mesquita, Paulo HC; Osburn, Shelby C; Vann, Christopher G; Lamb, Donald A; Sexton, Casey L; Candow, Darren G; Forbes, Scott C; Frugé, Andrew D; Kavazis, Andreas N; Young, Kaelin C; Seaborne, Robert A; Sharples, Adam P; Roberts, Michael DAbstractResistance training (RT) dynamically alters the skeletal muscle nuclear DNA methylome. However, no study has examined if RT affects the mitochondrial DNA (mtDNA) methylome. Herein, ten older, Caucasian untrained males (65 ± 7 y.o.) performed six weeks of full‐body RT (twice weekly). Body composition and knee extensor torque were assessed prior to and 72 h 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). Biochemical assays were also performed, and older male data were compared to younger trained males (22 ± 2 y.o., n = 7, n = 6 Caucasian & n = 1 African American). RT increased whole‐body lean tissue mass (p = .017), VL thickness (p = .012), and knee extensor torque (p = .029) in older males. RT also affected the mtDNA methylome, as 63% (159/254) of the CpG sites demonstrated reduced methylation (p < .05). Several mtDNA sites presented a more “youthful” signature in older males after RT in comparison to younger males. The 1.12 kilobase mtDNA D‐loop/control region, which regulates replication and transcription, possessed enriched hypomethylation in older males following RT. Enhanced expression of mitochondrial H‐ and L‐strand genes and complex III/IV protein levels were also observed (p < .05). While limited to a shorter‐term intervention, this is the first evidence showing that RT alters the mtDNA methylome in skeletal muscle. Observed methylome alterations may enhance mitochondrial transcription, and RT evokes mitochondrial methylome profiles to mimic younger men. The significance of these findings relative to broader RT‐induced epigenetic changes needs to be elucidated.Item Open Access Sarcoplasmic Hypertrophy in Skeletal Muscle: A Scientific “Unicorn” or Resistance Training Adaptation?(Frontiers in Physiology) Roberts, Michael D; Haun, Cody T; Vann, Christopher G; Osburn, Shelby C; Young, Kaelin CItem Open Access Skeletal muscle LINE-1 retrotransposon activity is upregulated in older versus younger rats(American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, 2019-09-01) Mumford, Petey W; Romero, Matthew A; Osburn, Shelby C; Roberson, Paul A; Vann, Christopher G; Mobley, Christopher B; Brown, Michael D; Kavazis, Andreas N; Young, Kaelin C; Roberts, Michael DLong interspersed element-1 (LINE-1) is a retrotransposon capable of replicating and inserting LINE-1 copies into the genome. Others have reported skeletal muscle LINE-1 markers are higher in older versus younger mice, but data are lacking in other species. Herein, gastrocnemius muscle from male Fischer 344 rats that were 3, 12, and 24 mo old ( n = 9 per group) were analyzed for LINE-1 mRNA, DNA, promoter methylation and DNA accessibility. qPCR primers were designed for active (L1.3) and inactive (L1.Tot) LINE-1 elements as well as part of the ORF1 sequence. L1.3, L1.Tot, and ORF1 mRNAs were higher ( P < 0.05) in 12/24 versus 3-mo-old rats. L1.3 DNA was higher in the 24-mo-old rats versus other groups, and ORF1 DNA was greater in 12/24 versus 3-mo-old rats. ORF1 protein was higher in 12/24 versus 3-mo-old rats. RNA-sequencing indicated mRNAs related to DNA methylation ( Tet1) and histone acetylation ( Hdac2) were lower in 24 versus 3-mo-old rats. L1.3 DNA accessibility was higher in 24-mo-old versus 3-mo-old rats. No age-related differences in nuclear histone deacetylase (HDAC) activity existed, although nuclear DNA methyltransferase (DNMT) activity was lower in 12/24 versus 3-mo-old rats ( P < 0.05). In summary, markers of skeletal muscle LINE-1 activity increase across the age spectrum of rats, and this may be related to deficits in DNMT activity and/or increased LINE-1 DNA accessibility.Item Open Access Skeletal Muscle Myofibrillar Protein Abundance Is Higher in Resistance-Trained Men, and Aging in the Absence of Training May Have an Opposite Effect(Sports) Vann, Christopher G; Roberson, Paul A; Osburn, Shelby C; Mumford, Petey W; Romero, Matthew A; Fox, Carlton D; Moore, Johnathon H; Haun, Cody; Beck, Darren T; Moon, Jordan R; Kavazis, Andreas N; Young, Kaelin C; Badisa, Veera LD; Mwashote, Benjamin M; Ibeanusi, Victor; Singh, Rakesh K; Roberts, Michael DResistance training generally increases skeletal muscle hypertrophy, whereas aging is associated with a loss in muscle mass. Interestingly, select studies suggest that aging, as well as resistance training, may lead to a reduction in the abundance of skeletal muscle myofibrillar (or contractile) protein (per mg tissue). Proteomic interrogations have also demonstrated that aging, as well as weeks to months of resistance training, lead to appreciable alterations in the muscle proteome. Given this evidence, the purpose of this small pilot study was to examine total myofibrillar as well as total sarcoplasmic protein concentrations (per mg wet muscle) from the vastus lateralis muscle of males who were younger and resistance-trained (denoted as YT, n = 6, 25 ± 4 years old, 10 ± 3 self-reported years of training), younger and untrained (denoted as YU, n = 6, 21 ± 1 years old), and older and untrained (denoted as OU, n = 6, 62 ± 8 years old). The relative abundances of actin and myosin heavy chain (per mg tissue) were also examined using SDS-PAGE and Coomassie staining, and shotgun proteomics was used to interrogate the abundances of individual sarcoplasmic and myofibrillar proteins between cohorts. Whole-body fat-free mass (YT > YU = OU), VL thickness (YT > YU = OU), and leg extensor peak torque (YT > YU = OU) differed between groups (p < 0.05). Total myofibrillar protein concentrations were greater in YT versus OU (p = 0.005), but were not different between YT versus YU (p = 0.325). The abundances of actin and myosin heavy chain were greater in YT versus YU (p < 0.05) and OU (p < 0.001). Total sarcoplasmic protein concentrations were not different between groups. While proteomics indicated that marginal differences existed for individual myofibrillar and sarcoplasmic proteins between YT versus other groups, age-related differences were more prominent for myofibrillar proteins (YT = YU > OU, p < 0.05: 7 proteins; OU > YT = YU, p < 0.05: 11 proteins) and sarcoplasmic proteins (YT = YU > OU, p < 0.05: 8 proteins; OU > YT&YU, p < 0.05: 29 proteins). In summary, our data suggest that modest (~9%) myofibrillar protein packing (on a per mg muscle basis) was evident in the YT group. This study also provides further evidence to suggest that notable skeletal muscle proteome differences exist between younger and older humans. However, given that our n-sizes are low, these results only provide a preliminary phenotyping of the reported protein and proteomic variables.Item Open Access Skeletal Muscle Ribosome and Mitochondrial Biogenesis in Response to Different Exercise Training Modalities(Frontiers in Physiology) Mesquita, Paulo HC; Vann, Christopher G; Phillips, Stuart M; McKendry, James; Young, Kaelin C; Kavazis, Andreas N; Roberts, Michael DSkeletal muscle adaptations to resistance and endurance training include increased ribosome and mitochondrial biogenesis, respectively. Such adaptations are believed to contribute to the notable increases in hypertrophy and aerobic capacity observed with each exercise mode. Data from multiple studies suggest the existence of a competition between ribosome and mitochondrial biogenesis, in which the first adaptation is prioritized with resistance training while the latter is prioritized with endurance training. In addition, reports have shown an interference effect when both exercise modes are performed concurrently. This prioritization/interference may be due to the interplay between the 5’ AMP-activated protein kinase (AMPK) and mechanistic target of rapamycin complex 1 (mTORC1) signaling cascades and/or the high skeletal muscle energy requirements for the synthesis and maintenance of cellular organelles. Negative associations between ribosomal DNA and mitochondrial DNA copy number in human blood cells also provide evidence of potential competition in skeletal muscle. However, several lines of evidence suggest that ribosome and mitochondrial biogenesis can occur simultaneously in response to different types of exercise and that the AMPK-mTORC1 interaction is more complex than initially thought. The purpose of this review is to provide in-depth discussions of these topics. We discuss whether a curious competition between mitochondrial and ribosome biogenesis exists and show the available evidence both in favor and against it. Finally, we provide future research avenues in this area of exercise physiology.Item Open Access Synergist ablation-induced hypertrophy occurs more rapidly in the plantaris than soleus muscle in rats due to different molecular mechanisms(American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, 2020-02-01) Roberts, Michael D; Mobley, Christopher B; Vann, Christopher G; Haun, Cody T; Schoenfeld, Brad J; Young, Kaelin C; Kavazis, Andreas NWe examined molecular mechanisms that were altered during rapid soleus (type I fiber-dominant) and plantaris (type II fiber-dominant) hypertrophy in rats. Twelve Wistar rats (3.5 mo old; 6 female, 6 male) were subjected to surgical right-leg soleus and plantaris dual overload [synergist ablation (SA)], and sham surgeries were performed on left legs (CTL). At 14 days after surgery, the muscles were dissected. Plantaris mass was 27% greater in the SA than CTL leg ( P < 0.001), soleus mass was 13% greater in the SA than CTL leg ( P < 0.001), and plantaris mass was higher than soleus mass in the SA leg ( P = 0.001). Plantaris total RNA concentrations and estimated total RNA levels (suggestive of ribosome density) were 19% and 47% greater in the SA than CTL leg ( P < 0.05), protein synthesis levels were 64% greater in the SA than CTL leg ( P = 0.038), and satellite cell number per fiber was 60% greater in the SA than CTL leg ( P = 0.003); no differences in these metrics were observed between soleus SA and CTL legs. Plantaris, as well as soleus, 20S proteasome activity was lower in the SA than CTL leg ( P < 0.05), although the degree of downregulation was greater in the plantaris than soleus muscle (−63% vs. −20%, P = 0.001). These data suggest that early-phase plantaris hypertrophy occurs more rapidly than soleus hypertrophy, which coincided with greater increases in ribosome biogenesis, protein synthesis, and satellite cell density, as well as greater decrements in 20S proteasome activity, in the plantaris muscle.Item Open Access The effects of resistance training with or without peanut protein supplementation on skeletal muscle and strength adaptations in older individuals(Journal of the International Society of Sports Nutrition, 2020-01-03) Lamb, Donald A; Moore, Johnathon H; Smith, Morgan A; Vann, Christopher G; Osburn, Shelby C; Ruple, Bradley A; Fox, Carlton D; Smith, Kristen S; Altonji, Olivia M; Power, Zade M; Cerovsky, Annsley E; Ross, C Owen; Cao, Andy T; Goodlett, Michael D; Huggins, Kevin W; Fruge, Andrew D; Young, Kaelin C; Roberts, Michael D