Reports using computed tomography (CT) to estimate thigh skeletal muscle cross-sectional area and mean muscle attenuation are often difficult to evaluate due to inconsistent methods of quantification ...and/or poorly described analysis methods. This CT tutorial provides step-by-step instructions in using free, NIH Image J software to quantify both muscle size and composition in the mid-thigh, which was validated against a robust commercially available software, SliceOmatic. CT scans of the mid-thigh were analyzed from 101 healthy individuals aged 65 and older. Mean cross-sectional area and mean attenuation values are presented across seven defined Hounsfield unit (HU) ranges along with the percent contribution of each region to the total mid-thigh area. Inter-software correlation coefficients ranged from R2 = 0.92-0.99 for all specific area comparisons measured using the Image J method compared to SliceOmatic. We recommend reporting individual HU ranges for all areas measured. Although HU range 0-100 includes the majority of skeletal muscle area, HU range -29 to 150 appears to be the most inclusive for quantifying total thigh muscle. Reporting all HU ranges is necessary to determine the relative contribution of each, as they may be differentially affected by age, obesity, disease, and exercise. This standardized operating procedure will facilitate consistency among investigators reporting computed tomography characteristics of the thigh on single slice images. Trial Registration: ClinicalTrials.gov NCT02308228.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Progressive resistance exercise training (PRT) is the most effective known intervention for combating aging skeletal muscle atrophy. However, the hypertrophic response to PRT is variable, and this ...may be due to muscle inflammation susceptibility. Metformin reduces inflammation, so we hypothesized that metformin would augment the muscle response to PRT in healthy women and men aged 65 and older. In a randomized, double‐blind trial, participants received 1,700 mg/day metformin (N = 46) or placebo (N = 48) throughout the study, and all subjects performed 14 weeks of supervised PRT. Although responses to PRT varied, placebo gained more lean body mass (p = .003) and thigh muscle mass (p < .001) than metformin. CT scan showed that increases in thigh muscle area (p = .005) and density (p = .020) were greater in placebo versus metformin. There was a trend for blunted strength gains in metformin that did not reach statistical significance. Analyses of vastus lateralis muscle biopsies showed that metformin did not affect fiber hypertrophy, or increases in satellite cell or macrophage abundance with PRT. However, placebo had decreased type I fiber percentage while metformin did not (p = .007). Metformin led to an increase in AMPK signaling, and a trend for blunted increases in mTORC1 signaling in response to PRT. These results underscore the benefits of PRT in older adults, but metformin negatively impacts the hypertrophic response to resistance training in healthy older individuals. ClinicalTrials.gov Identifier: NCT02308228.
Because metformin reduces inflammation, we hypothesized that it would augment the muscle response to progressive resistance exercise training (PRT) in healthy older participants. Following 14 weeks of PRT, metformin blunted gains in lean mass, thigh muscle mass, and thigh muscle density compared to placebo. Metformin did not affect increases in muscle macrophage abundance. However, metformin increased AMPK signaling, leading to a reduced mean increase in mTOR signaling.
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DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
Two new species of deepwater cardinalfish,
Epigonus gemma
7 specimens, 37.7–76.7 mm in standard length (SL) and
Epigonus hexacanthus
(22 specimens, 32.2–57.0 mm SL) are described based on specimens ...from deep reefs off Curaçao, southern Caribbean Sea.
Epigonus gemma
is distinguished from other congeners by a combination of the following characters: dorsal-fin rays VII-I, 9–10; pectoral-fin rays 16; total gill rakers 25–27; vertebrae 10 + 15; pyloric caeca 8–9; pored lateral-line scales 43–44 + 5–6; opercular spine absent; maxillary mustache-like processes absent; ribs on last abdominal vertebra absent; tongue toothless; endopterygoid teeth absent; and enlarged conical teeth on symphysis of lower jaw present.
Epigonus hexacanthus
is distinguished from other congeners by a combination of the following characters: dorsal-fin rays VI-I, 10; pectoral-fin rays 16–17; total gill rakers 25–27; vertebrae 10 + 15; pyloric caeca 6–7; pored lateral-line scales 32–35 + 3–5; opercular spine absent; maxillary mustache-like processes absent; ribs on last abdominal vertebra absent; lingual teeth present; endopterygoid teeth present; and enlarged conical teeth on symphysis of lower jaw absent. Eight specimens (37.6–54.4 mm SL) of
E. hexacanthus
are female with mature gonads, rendering the species the smallest in size at sexual maturity among its congeners. A key to the species of
Epigonus
currently known from the Caribbean Sea is provided.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
The extracellular matrix (ECM) in skeletal muscle plays an integral role in tissue development, structural support, and force transmission. For successful adaptation to mechanical loading, remodeling ...processes must occur. In a large cohort of older adults, transcriptomics revealed that genes involved in ECM remodeling, including matrix metalloproteinase 14 (MMP14), were the most upregulated following 14 weeks of progressive resistance exercise training (PRT). Using single‐cell RNA‐seq, we identified macrophages as a source of Mmp14 in muscle following a hypertrophic exercise stimulus in mice. In vitro contractile activity in myotubes revealed that the gene encoding cytokine leukemia inhibitory factor (LIF) is robustly upregulated and can stimulate Mmp14 expression in macrophages. Functional experiments confirmed that modulation of this muscle cell‐macrophage axis facilitated Type I collagen turnover. Finally, changes in LIF expression were significantly correlated with MMP14 expression in humans following 14 weeks of PRT. Our experiments reveal a mechanism whereby muscle fibers influence macrophage behavior to promote ECM remodeling in response to mechanical loading.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Area of muscle, fat, and bone is often measured in thigh CT scans when tissue composition is a key outcome. SliceOmatic software is commonly referenced for such analysis but published methods may be ...insufficient for new users. Thus, a quick start guide to calculating thigh composition using SliceOmatic has been developed.
CT images of the thigh were collected from older (69 ± 4 yrs, N = 24) adults before and after 12-weeks of resistance training. SliceOmatic was used to segment images into seven density regions encompassing fat, muscle, and bone from -190 to +2000 Hounsfield Units HU. The relative contributions to thigh area and the effects of tissue density overlap for skin and marrow with muscle and fat were determined.
The largest contributors to the thigh were normal fat (-190 to -30 HU, 29.1 ± 7.4%) and muscle (35 to 100 HU, 48.9 ± 8.2%) while the smallest were high density (101 to 150 HU, 0.79 ± 0.50%) and very high density muscle (151 to 200 HU, 0.07 ± 0.02%). Training significantly (P<0.05) increased area for muscle in the very low (-29 to -1 HU, 5.5 ± 7.9%), low (0 to 34 HU, 9.6 ± 16.8%), normal (35 to 100 HU, 4.2 ± 7.9%), and high (100 to 150 HU, 70.9 ± 80.6%) density ranges for muscle. Normal fat, very high density muscle and bone did not change (P>0.05). Contributions to area were altered by ~1% or less and the results of training were not affected by accounting for skin and marrow.
When using SliceOmatic to calculate thigh composition, accounting for skin and marrow may not be necessary. We recommend defining muscle as -29 to +200 HU but that smaller ranges (e.g. low density muscle, 0 to 34 HU) can easily be examined for relationships with the health condition and intervention of interest.
Clinicaltrials.gov NCT02261961.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
In older individuals, hypertrophy from progressive resistance training (PRT) is compromised in approximately one-third of participants in exercise trials. The objective of this study was to establish ...novel relationships between baseline muscle features and/or their PRT-induced change in vastus lateralis muscle biopsies with hypertrophy outcomes. Multiple linear regression analyses adjusted for sex were performed on phenotypic data from older adults (
= 48 participants, 70.8 ± 4.5 yr) completing 14 wk of PRT. Results show that baseline muscle size associates with growth regardless of hypertrophy outcome measure fiber cross-sectional area (fCSA), β = -0.76, Adj.
< 0.01; thigh muscle area by computed tomography (CT), β = -0.75, Adj.
< 0.01; dual-energy X-ray absorptiometry (DXA) thigh lean mass, β = -0.47, Adj.
< 0.05. Furthermore, loosely packed collagen organization (CO, β = -0.44, Adj.
< 0.05) and abundance of CD11b+/CD206- immune cells (β = -0.36, Adj.
= 0.10) were negatively associated with whole muscle hypertrophy, with a significant sex interaction on the latter. In addition, a composite hypertrophy score generated using all three measures reinforces significant fiber level findings that changes in myonuclei (MN) (β = 0.67, Adj.
< 0.01), changes in immune cells (β = 0.48, Adj.
< 0.05; both CD11b+/CD206+and CD11b+/CD206- cells), and capillary density (β = 0.56, Adj.
< 0.01) are significantly associated with growth. Exploratory single-cell RNA-sequencing of CD11b+ cells in muscle in response to resistance exercise showed that macrophages have a mixed phenotype. Collagen associations with macrophages may be an important aspect in muscle response heterogeneity. Detailed histological phenotyping of muscle combined with multiple measures of growth response to resistance training in older persons identify potential new mechanisms underlying response heterogeneity and possible sex differences.
Extensive analyses of muscle features associated with muscle size and resistance training response in older persons, including sex differences, and evaluation of multiple measures of hypertrophy are discussed. Collagen organization and CD11b-expressing immune cells offer potential new targets to augment growth response in older individuals. A hypertrophy composite score reveals that changes in immune cells, myonuclei, and capillary density are critically important for overall muscle growth while sc-RNAseq reveals evidence for macrophage heterogeneity.
Changes in skeletal muscle are an important aspect of overall health. The collection of human muscle to study cellular and molecular processes for research requires a needle biopsy procedure which, ...in itself, can induce changes in the tissue. To investigate the effect of repeat tissue sampling, we collected skeletal muscle biopsy samples from vastus lateralis separated by 7 days. Cellular infiltrate, central nucleation, enlarged extracellular matrix, and rounding of muscle fibers were used as indices to define muscle damage, and we found that 16/26 samples (61.5%) revealed at least two of these symptoms in the secondary biopsy. The presence of damage influenced outcome measures usually obtained in human biopsies. Damaged muscle showed an increase in the number of small fibers even though average fiber and fiber type-specific cross-sectional area (CSA) were not different. This included higher numbers of embryonic myosin heavy chain-positive fibers (
= 0.001) as well as elevated satellite cell number (
= 0.02) in the damaged areas and higher variability in satellite cell count in the total area (
= 0.04). Collagen content was higher in damaged (
= 0.0003) as well as nondamaged areas (
= 0.05) of the muscle sections of the damaged compared with the nondamaged group. Myofibrillar protein and ribonucleic acid (RNA) fractional synthesis rates were not significantly different between the damaged compared with the nondamaged group. Results indicate that common outcomes as well as outcome variability in human muscle tissue are affected by previous biopsies. Therefore, the extent of potential damage should be assessed when performing repeated biopsies.
Indices of damage can be found in repeated biopsy samples of nonintervened control legs. Variables, directly and not directly related to muscle damage or regeneration, were compromised in second biopsy. There is a need to determine potential damage within muscle tissue when repeated muscle sampling is part of the study design. Muscle biopsy sampling may be a source of increased heterogeneity in human muscle data.
PURPOSEThis study assessed how individuals compensate for energy expended during a 12-wk aerobic exercise intervention, elucidating potential mechanisms and the role exercise dose plays in the ...compensatory response.
PARTICIPANTS AND DESIGNThree-arm, randomized controlled trial among sedentary adults age 18 to 40 yr, body mass index of 25 to 35. Groups included six exercise sessions per week, two sessions per week, and sedentary control.
METHODSRate of exercise energy expenditure was calculated from a graded exercise test averaged across five heart rate zones. Energy compensation was calculated as the difference between expected weight loss (based on exercise energy expenditure) and changes in fat and fat-free mass (DXA). Resting energy expenditure was assessed via indirect calorimetry and concentrations of acylated ghrelin, leptin, insulin, and Glucagon-like peptide 1 (GLP-1) were assessed fasting and postprandial (six timepoints over 2 h).
RESULTSThe 6-d·wk group expended more energy (2753.5 kcal) and exercised longer (320.5 min) per week than the 2-d·wk group (1490.7 kcal, 1888.8 min, P < 0.05), resulting in greater fat loss compared with the 2-d or control groups (P < 0.05). Exercise groups did not differ in the % or total kcal compensated. Greater decreases in area under the curve (AUC) for acylated ghrelin predicted greater fat loss, regardless of group, energy expended per week, exercise duration, or exercise intensity. Changes in leptin AUC was the only independent predictor for energy compensation, with a greater decrease in leptin AUC predicting less energy compensation. Exercise frequency, energy expended, duration, or intensity did not influence energy compensation.
CONCLUSIONSLeptin is an important factor in successful weight loss through exercise, with greater postprandial decreases promoting less compensation. Greater amounts of exercise do not influence the compensatory response to an exercise-induced energy deficit.
Metformin and statins are currently the focus of large clinical trials testing their ability to counter age-associated declines in health, but recent reports suggest that both may negatively affect ...skeletal muscle response to exercise. However, it has also been suggested that metformin may act as a possible protectant of statin-related muscle symptoms. The potential impact of combined drug use on the hypertrophic response to resistance exercise in healthy older adults has not been described. We present secondary statin analyses of data from the MASTERS trial where metformin blunted the hypertrophy response in healthy participants (>65 years) following 14 weeks of progressive resistance training (PRT) when compared to identical placebo treatment (
= 94). Approximately one-third of MASTERS participants were taking prescribed statins. Combined metformin and statin resulted in rescue of the metformin-mediated impaired growth response to PRT but did not significantly affect strength. Improved muscle fiber growth may be associated with medication-induced increased abundance of CD11b+/CD206+ M2-like macrophages. Sarcopenia is a significant problem with aging and this study identifies a potential interaction between these commonly used drugs which may help prevent metformin-related blunting of the beneficial effects of PRT.
ClinicalTrials.gov, NCT02308228, Registered on 25 November 2014.
Otospermophilus douglasii (Richardson, 1829), the Douglas ground squirrel, was first described as a species and then relegated to a subspecies of the California ground squirrel, O. beecheyi ...(Richardson, 1829). However, genetic data recently were interpreted as indicative of returning O. douglasii back to valid species status. This semi-fossorial, social species is brown with small white spots, a dark dorsal patch, and silvery shoulders. Occupying diverse habitats and elevations, this native species is an important prey species and is most abundant in grasslands and open woodlands. It forages primarily on seeds and vegetation but is also in conflict with humans as a crop pest and disease vector that damages infrastructure through creating elaborate burrow systems. Currently, the International Union for Conservation of Nature has not provided a conservation assessment for O. douglasii.
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