Browsing by Author "Kavazis, Andreas N"
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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 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 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 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 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 mitochondrial volume and myozenin-1 protein differences exist between high versus low anabolic responders to resistance training(PeerJ) Roberts, Michael D; Romero, Matthew A; Mobley, Christopher B; Mumford, Petey W; Roberson, Paul A; Haun, Cody T; Vann, Christopher G; Osburn, Shelby C; Holmes, Hudson H; Greer, Rory A; Lockwood, Christopher M; Parry, Hailey A; Kavazis, Andreas NBackgroundWe sought to examine how 12 weeks of resistance exercise training (RET) affected skeletal muscle myofibrillar and sarcoplasmic protein levels along with markers of mitochondrial physiology in high versus low anabolic responders.MethodsUntrained college-aged males were classified as anabolic responders in the top 25th percentile (high-response cluster (HI);n= 13, dual x-ray absorptiometry total body muscle mass change (Δ) = +3.1 ± 0.3 kg, Δ vastus lateralis (VL) thickness = +0.59 ± 0.05 cm, Δ muscle fiber cross sectional area = +1,426 ± 253 μm2) and bottom 25th percentile (low-response cluster (LO);n= 12, +1.1 ± 0.2 kg, +0.24 ± 0.07 cm, +5 ± 209 μm2;p< 0.001 for all Δ scores compared to HI). VL muscle prior to (PRE) and following RET (POST) was assayed for myofibrillar and sarcoplasmic protein concentrations, myosin and actin protein content, and markers of mitochondrial volume. Proteins related to myofibril formation, as well as whole lysate PGC1-α protein levels were assessed.ResultsMain effects of cluster (HI > LO,p= 0.018, Cohen’sd= 0.737) and time (PRE > POST,p= 0.037, Cohen’sd= −0.589) were observed for citrate synthase activity, although no significant interaction existed (LO PRE = 1.35 ± 0.07 mM/min/mg protein, LO POST = 1.12 ± 0.06, HI PRE = 1.53 ± 0.11, HI POST = 1.39 ± 0.10). POST myofibrillar myozenin-1 protein levels were up-regulated in the LO cluster (LO PRE = 0.96 ± 0.13 relative expression units, LO POST = 1.25 ± 0.16, HI PRE = 1.00 ± 0.11, HI POST = 0.85 ± 0.12; within-group LO increasep= 0.025, Cohen’sd= 0.691). No interactions or main effects existed for other assayed markers.DiscussionOur data suggest myofibrillar or sarcoplasmic protein concentrations do not differ between HI versus LO anabolic responders prior to or following a 12-week RET program. Greater mitochondrial volume in HI responders may have facilitated greater anabolism, and myofibril myozenin-1 protein levels may represent a biomarker that differentiates anabolic responses to RET. However, mechanistic research validating these hypotheses is needed.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.