| 1. |
- Bass, Joseph J., et al.
(författare)
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Overexpression of the vitamin D receptor (VIM) induces skeletal muscle hypertrophy
- 2020
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Ingår i: Molecular Metabolism. - : Elsevier. - 2212-8778. ; 42
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The Vitamin D receptor (VDR) has been positively associated with skeletal muscle mass, function and regeneration. Mechanistic studies have focused on the loss of the receptor, with in vivo whole-body knockout models demonstrating reduced myofibre size and function and impaired muscle development. To understand the mechanistic role upregulation of the VDR elicits in muscle mass/health, we studied the impact of VDR over-expression (OE) in vivo before exploring the importance of VDR expression upon muscle hypertrophy in humans.Methods: Wistar rats underwent in vivo electrotransfer (IVE) to overexpress the VDR in the Tibialis anterior (TA) muscle for 10 days, before comprehensive physiological and metabolic profiling to characterise the influence of VDR-OE on muscle protein synthesis (MPS), anabolic signalling and satellite cell activity. Stable isotope tracer (D2O) techniques were used to assess sub-fraction protein synthesis, alongside RNA-Seq analysis. Finally, human participants underwent 20 wks of resistance exercise training, with body composition and transcriptomic analysis.Results: Muscle VDR-OE yielded total protein and RNA accretion, manifesting in increased myofibre area, i.e., hypertrophy. The observed increases in MPS were associated with enhanced anabolic signalling, reflecting translational efficiency (e.g., mammalian target of rapamycin (mTOR-signalling), with no effects upon protein breakdown markers being observed. Additionally, RNA-Seq illustrated marked extracellular matrix (ECM) remodelling, while satellite cell content, markers of proliferation and associated cell-cycled related gene-sets were upregulated. Finally, induction of VDR mRNA correlated with muscle hypertrophy in humans following long-term resistance exercise type training.Conclusion: VDR-OE stimulates muscle hypertrophy ostensibly via heightened protein synthesis, translational efficiency, ribosomal expansion and upregulation of ECM remodelling-related gene-sets. Furthermore, VDR expression is a robust marker of the hypertrophic response to resistance exercise in humans. The VDR is a viable target of muscle maintenance through testable Vitamin D molecules, as active molecules and analogues. (C) 2020 The Author(s). Published by Elsevier GmbH.
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| 2. |
- Bass, Joseph J., et al.
(författare)
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The mechanisms of skeletal muscle atrophy in response to transient knockdown of the vitamin D receptor in vivo
- 2021
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Ingår i: Journal of Physiology. - : John Wiley & Sons. - 0022-3751 .- 1469-7793. ; 599:3, s. 963-979
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Tidskriftsartikel (refereegranskat)abstract
- KEY POINTS:Reduced vitamin D receptor (VDR) expression prompts skeletal muscle atrophy.Atrophy occurs through catabolic processes, namely the induction of autophagy, while anabolism remains unchanged.In response to VDR-KD mitochondrial function and related gene-set expression is impaired.In vitro VDR knockdown induces myogenic dysregulation occurring through impaired differentiation.These results highlight the autonomous role the VDR has within skeletal muscle mass regulation.Objective: Vitamin-D deficiency is estimated to affect ∼40% of the world's population and has been associated with impaired muscle maintenance. Vitamin-D exerts its actions through the Vitamin-D-receptor (VDR), the expression of which was recently confirmed in skeletal muscle, and its down-regulation is linked to reduced muscle mass and functional decline. To identify potential mechanisms underlying muscle atrophy, we studied the impact of VDR knockdown (KD) on mature skeletal muscle in vivo, and myogenic regulation in vitro in C2C12 cells.Methods: Male Wistar rats underwent in vivo electrotransfer (IVE) to knock down the VDR in hind-limb tibialis anterior (TA) muscle for 10 days. Comprehensive metabolic and physiological analysis was undertaken to define the influence loss of the VDR on muscle fibre composition, protein synthesis, anabolic and catabolic signalling, mitochondrial phenotype, and gene expression. Finally, in vitro lentiviral transfection was used to induce sustained VDR-KD in C2C12 cells to analyse myogenic regulation.Results: Muscle VDR-KD elicited atrophy through a reduction in total protein content, resulting in lower myofibre area. Activation of autophagic processes was observed, with no effect upon muscle protein synthesis or anabolic signalling. Furthermore, RNA-Seq analysis identified systematic down-regulation of multiple mitochondrial respiration related protein and genesets. Finally, in vitro VDR-knockdown impaired myogenesis (cell cycling, differentiation and myotube formation).Conclusion: Taken together, these data indicate a fundamental regulatory role of the VDR in the regulation of myogenesis and muscle mass; whereby it acts to maintain muscle mitochondrial function and limit autophagy.
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| 3. |
- Deane, Colleen S., et al.
(författare)
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The acute transcriptional response to resistance exercise : impact of age and contraction mode
- 2019
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Ingår i: Aging. - : Impact Journals LLC. - 1945-4589 .- 1945-4589. ; 11:7, s. 2111-2126
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Tidskriftsartikel (refereegranskat)abstract
- Optimization of resistance exercise (RE) remains a hotbed of research for muscle building and maintenance. However, the interactions between the contractile components of RE (i.e. concentric (CON) and eccentric (ECC)) and age, are poorly defined. We used transcriptomics to compare age-related molecular responses to acute CON and ECC exercise. Eight young (21 +/- 1 y) and eight older (70 +/- 1 y) exercise-naive male volunteers had vastus lateralis biopsies collected at baseline and 5 h post unilateral CON and contralateral ECC exercise. RNA was subjected to next-generation sequencing and differentially expressed (DE) genes tested for pathway enrichment using Gene Ontology (GO). The young transcriptional response to CON and ECC was highly similar and older adults displayed moderate contraction-specific profiles, with no GO enrichment. Age-specific responses to ECC revealed 104 DE genes unique to young, and 170 DE genes in older muscle, with no GO enrichment. Following CON, 15 DE genes were young muscle-specific, whereas older muscle uniquely expressed 147 up-regulated genes enriched for cell adhesion and blood vessel development, and 28 down-regulated genes involved in mitochondria! respiration, amino acid and lipid metabolism. Thus, older age is associated with contraction-specific regulation often without clear functional relevance, perhaps reflecting a degree of stochastic age-related dysregulation.
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| 4. |
- Willis, Craig R.G., et al.
(författare)
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Network analysis of human muscle adaptation to aging and contraction
- 2020
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Ingår i: Aging. - : Impact Journals LLC. - 1945-4589 .- 1945-4589. ; 12:1, s. 740-755
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Tidskriftsartikel (refereegranskat)abstract
- Resistance exercise (RE) remains a primary approach for minimising aging muscle decline. Understanding muscle adaptation to individual contractile components of RE (eccentric, concentric) might optimise RE-based intervention strategies. Herein, we employed a network-driven pipeline to identify putative molecular drivers of muscle aging and contraction mode responses. RNA-sequencing data was generated from young (21±1 y) and older (70±1 y) human skeletal muscle before and following acute unilateral concentric and contralateral eccentric contractions. Application of weighted gene co-expression network analysis identified 33 distinct gene clusters ('modules') with an expression profile regulated by aging, contraction and/or linked to muscle strength. These included two contraction 'responsive' modules (related to 'cell adhesion' and 'transcription factor' processes) that also correlated with the magnitude of post-exercise muscle strength decline. Module searches for 'hub' genes and enriched transcription factor binding sites established a refined set of candidate module-regulatory molecules (536 hub genes and 60 transcription factors) as possible contributors to muscle aging and/or contraction responses. Thus, network-driven analysis can identify new molecular candidates of functional relevance to muscle aging and contraction mode adaptations.
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| 5. |
- Madrigal, Pedro, et al.
(författare)
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Revamping Space-omics in Europe
- 2020
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Ingår i: CELL SYSTEMS. - : Elsevier BV. - 2405-4712. ; 11:6, s. 555-556
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Tidskriftsartikel (refereegranskat)
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| 6. |
- Manzano, Aránzazu, et al.
(författare)
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Enhancing European capabilities for application of multi-omics studies in biology and biomedicine space research
- 2023
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Ingår i: iScience. - : Elsevier BV. - 2589-0042. ; 26:9
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Forskningsöversikt (refereegranskat)abstract
- Following on from the NASA twins’ study, there has been a tremendous interest in the use of omics techniques in spaceflight. Individual space agencies, NASA's GeneLab, JAXA's ibSLS, and the ESA-funded Space Omics Topical Team and the International Standards for Space Omics Processing (ISSOP) groups have established several initiatives to support this growth. Here, we present recommendations from the Space Omics Topical Team to promote standard application of space omics in Europe. We focus on four main themes: i) continued participation in and coordination with international omics endeavors, ii) strengthening of the European space omics infrastructure including workforce and facilities, iii) capitalizing on the emerging opportunities in the commercial space sector, and iv) capitalizing on the emerging opportunities in human subjects research.
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