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Biology subjects

Hoffman, E. P.

Publications and source records attributed to Hoffman, E. P..

4 recordsLinked to original sources

Muscle Strength and Size Relationships with Unilateral Progressive Resistance Training

PurposeThis study defines correlative and causal relationships between muscle strength and size before and after unilateral resistance training (RT) in a large cohort of healthy adults, focusing on sex differences within these relationships. MethodsResults from 1233 participants (504 males and 729 females) in a retrospective analysis were included. Maximal voluntary isometric contraction strength (MVC), one-repetition maximum strength (1RM), biceps cross-sectional area (CSA) and elbow flexor volume (VOL) measures of the non-dominant and dominant arm were evaluated from baseline and after 12-wk RT twice per week. Correlations of MVC and VOL and 1RM and VOL were calculated in the whole cohort and within each sex independently. Causal analysis modeling was used to infer mechanistic relationships among variables. ResultsAbsolute muscle strength and size related to one another both at baseline and following training, however correlation strength in each sex were weak. After RT, MVC relative change and VOL relative change correlations were correlated for the whole cohort (r=0.16; p<0.001) and females (r=0.18; p<0.001), but not in males (r=0.11; p=0.07). No significant correlations for relative change in 1RM and VOL were observed for the whole cohort or within sex. Causal discovery determined that change in VOL caused significant change in 1RM (but not MVC) and age was identified as a potential cause. ConclusionsSex differences occur in muscle size and strength relationship adaptations following resistance training, most notably the absence of significant relationships between relative size and strength changes in men. Simpsons paradox bias, where assessing the combined data of males and females (also affecting overall sample size) affects identifies patterns differently than assessing relationships within each sex, may partially explain our findings.

physiology↗

Human muscle stem cells are refractory to aging

Age-related loss of muscle mass and strength is widely attributed to limitation in the capacity of muscle resident satellite cells to perform their myogenic function. This idea contains two notions that have not been comprehensively evaluated by experiment. First, it entails the idea that we damage and lose substantial amounts of muscle in the course of our normal daily activities. Second, it suggests that mechanisms of muscle repair are in some way exhausted, thus limiting muscle regeneration. A third option is that the aged environment becomes inimical to the conduct of muscle regeneration. In the present study we used our established model of human muscle xenografting to test whether muscle samples taken from cadavers, of a range of ages, maintained their myogenic potential after being transplanted into immunodeficient mice. We find no measurable difference in regeneration across the range of ages investigated up to 78 years of age. Moreover, we report that satellite cells maintained their myogenic capacity even when muscles were grafted 11 days postmortem in our model. We conclude that the loss of muscle mass with increasing age is not attributable to any intrinsic loss of myogenicity and is most likely a reflection of progressive and detrimental changes in the muscle micro-environment such as to disfavor the myogenic function of these cells.

cell biology↗

Integrated Identification of Disease Specific Pathways Using Multi-omics data

MotivationIdentification of biological pathways plays a central role in understanding both human health and diseases. Although much work has previously been done to explore the biological pathways by using single omics data, little effort has been reported using multi-omics data integration, mainly due to methodological and technological limitations. Compared to single omics data, multi-omics data will help identifying disease specific functional pathways with both higher sensitivity and specificity, thus gaining more comprehensive insights into the molecular architecture of disease processes.\n\nResultsIn this paper, we propose two computational approaches that integrate multi-omics data and identify disease-specific biological pathways with high sensitivity and specificity. Applying our methods to an experimental multi-omics data dataset on muscular dystrophy subtypes, we identified disease-specific pathways of high biological plausibility. The developed methodology will likely have a broad impact on improving the molecular characterization of many common diseases.\n\nContactyuewang@vt.edu\n\nSupplementary informationSupplementary information attached.

bioinformatics↗

High-resolution mass spectrometry-based non-targeted metabolomic discovery of disease and glucocorticoid biomarkers in an animal model of muscular dystrophy

Urine is increasingly being considered as a source of biomarker development in Duchenne Muscular Dystrophy (DMD), a severe, life-limiting disorder that affects approximately 1 in 4500 boys. In this study, we used the mdx mice--a murine model of DMD--to discover biomarkers of disease, as well as pharmacodynamic biomarkers responsive to prednisolone, commonly used to treat DMD. Longitudinal urine samples were analyzed from male age-matched mdx and wild-type mice randomized to prednisolone or vehicle. We used high-resolution mass spectrometry to discover metabolic biomarkers of both disease and glucocorticoid treatment. A large number of metabolites (869 out of 6,334) were found to be significantly different between mdx and wild-type mice at baseline (Bonferroni-adjusted p-value < 0.05), thus being associated with disease status. These included a peak with m/z=357 and creatine, which were also discovered in a previous human study looking at serum. Novel observations included biliverdin and hypusine. These four peaks were also significantly higher in mdx mice compared to wild-type, as well as significantly associated with time after the baseline. Creatine and biliverdin were also associated with treatment after the baseline, but the association with creatine may have been driven by an imbalance at baseline. In conclusion, our study reports a number of biomarkers, both known and novel, which may be related to either the mechanisms of muscle injury in DMD and/or prednisolone treatment.

bioinformatics↗