| 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. |
- Bauset, Celia, et al.
(författare)
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Nuts and Metabolic Syndrome : Reducing the Burden of Metabolic Syndrome in Menopause
- 2022
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Ingår i: Nutrients. - : MDPI. - 2072-6643. ; 14:8
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Forskningsöversikt (refereegranskat)abstract
- Menopause imposes a dramatic fall in estrogens, which is followed by an increase in the proportion of fat. The rising androgen/estrogen ratio along the menopause transition favors the accumulation of central fat, which contributes to insulin resistance and a series of concatenated effects, leading to a higher incidence of metabolic syndrome. The modulatory effect of diet on the metabolic syndrome phenotype has been shown for the Mediterranean diet, and nuts are key determinants of these health benefits. This review of the impact of nuts on the risk factors of the metabolic syndrome cluster examined studies-prioritizing meta-analyses and systemic reviews-to summarize the potential benefits of nut ingestion on the risk of metabolic syndrome associated with menopause. Nuts have a general composition profile that includes macronutrients, with a high proportion of unsaturated fat, bioactive compounds, and fiber. The mechanisms set in motion by nuts have shown different levels of efficacy against the disturbances associated with metabolic syndrome, but a beneficial impact on lipids and carbohydrate metabolism, and a potential, but minimal reduction in blood pressure and fat accumulation have been found.
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| 4. |
- Bergens, Oscar, 1991-, et al.
(författare)
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Associations between Circulating Inflammatory Biomarkers and Indicators of Muscle Health in Older Men and Women
- 2021
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Ingår i: Journal of Clinical Medicine. - : MDPI. - 2077-0383. ; 10:22
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Tidskriftsartikel (refereegranskat)abstract
- Systemic inflammation is believed to contribute to declining muscle health during aging. The present study aims to examine associations between indicators of muscle health and pro- and anti-inflammatory biomarkers in older men and women, while also considering the impacts of physical activity and protein intake. An assessment of skeletal muscle index (SMI) by bioelectrical impedance analysis, handgrip strength, and 5-sit-to-stand time, using standardized procedures, was conducted in a population of older men (n = 90) and women (n = 148) aged 65-70 years. The inflammatory biomarkers C-reactive protein (CRP), fibrinogen, interleukin (IL)-6, IL-10, IL-18, tumor necrosis factor (TNF)-α, monocyte chemoattractant protein-1, and macrophage inflammatory protein-1α were assessed in blood samples. Data were analyzed and stratified according to biological sex using multiple linear regression models. In older women, SMI was inversely associated with the pro-inflammatory markers CRP (β = -0.372; p < 0.05), fibrinogen (β = -0.376; p < 0.05), and IL-6 (β = -0.369; p < 0.05). Importantly, these associations were independent of abdominal adiposity (waist circumference), protein intake, physical activity level, as well as any adherence to muscle strengthening guidelines (≥2 sessions/week). In contrast, no corresponding associations were observed in men. In conclusion, our findings indicate the detrimental influence of a pro-inflammatory environment on muscle health regardless of important lifestyle-related factors in older women. However, the lack of such associations in older men highlights the importance of considering biological sex when examining the complex interaction between the systemic inflammatory environment and muscle health.
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| 5. |
- Bergens, Oscar, 1991-
(författare)
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Chronic Systemic Inflammation, Body Composition and Physical Activity Behaviours in Older Adults
- 2022
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Ageing is associated with a gradual physical decline accompanied by changes in body composition. The occurrence of a low-grade yet chronic state of systemic inflammation has gained interest for its potential consequences in the ageing process. Importantly, a physically active lifestyle may promote the maintenance of muscle mass, reduction in adipose tissue, and alleviate progression of a chronic pro-inflammatory state. The overall aim of this thesis was to explore relationships between biomarkers of systemic inflammation, body composition, and physical activity behaviours in community-dwelling older adults aged 65 to 70 years.A main finding of the thesis is the existence of associations between body composition and systemic inflammation in older adults, where excess adipose tissue is adversely associated with levels of inflammatory biomarkers in older women. Inverse associations were also observed between muscle mass and levels of pro-inflammatory biomarkers in older women. This thesis also highlights sex-specific associations between systemic inflammation and physical activity behaviours. Longer time spent sedentary was also associated with higher levels of proinflammatory biomarkers in older women and lower level of antiinflammatory biomarkers in older men. Reallocating time spent in activities of lower intensities with higher intensities was associated with lower levels of pro-inflammatory biomarkers in older women. Overall, the findings of this thesis support efforts promoting physical activity at the expense of sedentary time in order to combat age-related systemic inflammation and metabolic risk in older adults.
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| 6. |
- Bergens, Oscar, 1991-, et al.
(författare)
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Impact of healthy diet and physical activity on metabolic health in men and women : Study Protocol Clinical Trial (SPIRIT Compliant)
- 2020
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Ingår i: Medicine. - : Wolters Kluwer. - 0025-7974 .- 1536-5964. ; 99:16
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Healthy dietary patterns and physical activity (PA) represent important lifestyle behaviors with considerable potential to influence on age-related metabolic health. Yet, data on the combined effects of these lifestyle behaviors on metabolic health including low-grade systemic inflammation in aging populations remain scarce. Therefore, this protocol describes a randomized controlled trial aiming to examine the impacts of healthy dietary patterns alone or combined with PA on metabolic health in middle-aged and older men and women. Material and methods: The ORUDIET study is a 3-arm randomized controlled 16-week trial: Healthy Diet (HD), Healthy diet plus PA (HD-PA), and control (CON). The trial is open label, randomized with allocation concealment, parallel groups with passive controls. Participants without overt disease aged between 55 and 70 years, with BMI below 35, a current intake of a maximum of 1 serving of fruit and vegetable per day, and noncompliance to PA guidelines are eligible for inclusion. Participants in HD are instructed to increase fruit and vegetable intake to 5 servings per day (equivalent to 500 g). Participants in HD-PA receive the same dietary intervention as the HD and are additionally instructed to engage in moderate-to-vigorous physical activities for at least 150 minutes per week. The primary study outcomes are changes in metabolic and inflammatory health biomarkers. Secondary outcomes are changes in body composition and perceived health. Ethics and dissemination: The study protocol has been approved by the ethical review board in Uppsala, Sweden. The results will be published in peer-reviewed journals and disseminated in national and international conferences.
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| 7. |
- Bergens, Oscar, 1991-, et al.
(författare)
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Sedentary Patterns and Systemic Inflammation : Sex-Specific Links in Older Adults
- 2021
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Ingår i: Frontiers in Physiology. - : Frontiers Media S.A.. - 1664-042X. ; 12
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Tidskriftsartikel (refereegranskat)abstract
- The study aimed to examine sex-specific associations between objectively measured sedentary patterns and pro- and anti-inflammatory biomarkers in older adults when considering the moderating impact of physical activity (PA). Accelerometer-based monitoring of sedentary patterns and PA was conducted in a population of older men (n = 83; age: 67.4 ± 1.5; height: 178.7 ± 6.6 cm; weight: 80.9 ± 10.6 kg) and women (n = 146; age: 67.4 ± 1.6; height: 164.2 ± 6.1 cm; weight: 64.6 ± 10.1 kg) aged 65-70. Blood samples were collected for the assessment of the inflammatory biomarkers C-reactive protein (CRP), fibrinogen, interleukin-6 (IL-6), IL-10, IL-18, and monocyte chemoattractant protein-1 (MCP-1). Data were analyzed using multiple linear regression models. Total and bouts of ≥10 min of sedentary time were inversely associated with the anti-inflammatory marker IL-10 in older men (accumulated sedentary time: β = -0.116; bouts: β = -0.099; all p < 0.05). Associations were independent of moderate-to-vigorous physical activity (MVPA) and total PA volume. In women, total and bouts of ≥10 min of sedentary time were detrimentally associated with the pro-inflammatory marker fibrinogen (accumulated sedentary time: β = -0.130; bouts: β = -0.085; all p < 0.05). Associations remained between accumulated sedentary time and fibrinogen when adjusting for MVPA and total PA volume. This study highlights sex-specific routes by which sedentary patterns impact on pro- and anti-inflammatory biomarkers in older adults. The findings support efforts to promote accumulation of time spent in PA at the expense of time in sedentary pursuits on low-grade inflammation in older men and women.
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| 8. |
- Brook, Matthew S, et al.
(författare)
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Neither myonuclear accretion nor a myonuclear domain size ceiling is a feature of the attenuated hypertrophic potential of aged human skeletal muscle
- 2023
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Ingår i: GeroScience. - : Springer. - 2509-2715 .- 2509-2723. ; 45, s. 451-462
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Tidskriftsartikel (refereegranskat)abstract
- Ageing limits growth capacity of skeletal muscle (e.g. in response to resistance exercise), but the role of satellite cell (SC) function in driving this phenomenon is poorly defined. Younger (Y) (~ 23 years) and older (O) men (~ 69 years) (normal-weight BMI) underwent 6 weeks of unilateral resistance exercise training (RET). Muscle biopsies were taken at baseline and after 3-/6-week training. We determined muscle size by fibre CSA (and type), SC number, myonuclei counts and DNA synthesis (via D2O ingestion). At baseline, there were no significant differences in fibre areas between Y and O. RET increased type I fibre area in Y from baseline at both 3 weeks and 6 weeks (baseline: 4509 ± 534 µm2, 3 weeks; 5497 ± 510 µm2 P < 0.05, 6 weeks; 5402 ± 352 µm2 P < 0.05), whilst O increased from baseline at 6 weeks only (baseline 5120 ± 403 µm2, 3 weeks; 5606 ± 620 µm2, 6 weeks; 6017 ± 482 µm2 P < 0.05). However, type II fibre area increased from baseline in Y at both 3 weeks and 6 weeks (baseline: 4949 ± 459 µm2, 3 weeks; 6145 ± 484 µm2 (P < 0.01), 6 weeks; 5992 ± 491 µm2 (P < 0.01), whilst O showed no change (baseline 5210 ± 410 µm2, 3 weeks; 5356 ± 535 µm2 (P = 0.9), 6 weeks; 5857 ± 478 µm2 (P = 0.1). At baseline, there were no differences in fibre myonuclei number between Y and O. RET increased type I fibre myonuclei number from baseline in both Y and O at 3 weeks and 6 weeks with RET (younger: baseline 2.47 ± 0.16, 3 weeks; 3.19 ± 0.16 (P < 0.001), 6 weeks; 3.70 ± 0.29 (P < 0.0001); older: baseline 2.29 ± 0.09, 3 weeks; 3.01 ± 0.09 (P < 0.001), 6 weeks; 3.65 ± 0.18 (P < 0.0001)). Similarly, type II fibre myonuclei number increased from baseline in both Y and O at 3 weeks and 6 weeks (younger: baseline 2.49 ± 0.14, 3 weeks; 3.31 ± 0.21 (P < 0.001), 6 weeks; 3.86 ± 0.29 (P < 0.0001); older: baseline 2.43 ± 0.12, 3 weeks; 3.37 ± 0.12 (P < 0.001), 6 weeks; 3.81 ± 0.15 (P < 0.0001)). DNA synthesis rates %.d-1 exhibited a main effect of training but no age discrimination. Declines in myonuclei addition do not underlie impaired muscle growth capacity in older humans, supporting ribosomal and proteostasis impairments as we have previously reported.
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| 9. |
- Brook, M. S., et al.
(författare)
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Omega-3 supplementation during unilateral resistance exercise training in older women : A within subject and double-blind placebo-controlled trial
- 2021
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Ingår i: Clinical Nutrition ESPEN. - : Elsevier. - 2405-4577. ; 46, s. 394-404
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND & AIMS: The skeletal muscle anabolic effects of n-3 polyunsaturated fatty acids (n-3 PUFA) appear favoured towards women; a property that could be exploited in older women who typically exhibit poor muscle growth responses to resistance exercise training (RET). Here we sought to generate novel insights into the efficacy and mechanisms of n-3 PUFA alongside short-term RET in older women.METHODS: We recruited 16 healthy older women (Placebo n = 8 (PLA): 67±1y, n-3 PUFA n = 8: 64±1y) to a randomised double-blind placebo-controlled trial (n-3 PUFA; 3680 mg/day versus PLA) of 6 weeks fully-supervised progressive unilateral RET (i.e. 6 × 8 reps, 75% 1-RM, 3/wk-1). Strength was assessed by knee extensor 1-RM and isokinetic dynamometry ∼ every 10 d. Thigh fat free mass (TFFM) was measured by DXA at 0/3/6 weeks. Bilateral vastus lateralis (VL) biopsies at 0/2/4/6 weeks with deuterium oxide (D2O) dosing were used to determine MPS responses for 0-2 and 4-6 weeks. Further, fibre cross sectional area (CSA), myonuclei number and satellite cell (SC) number were assessed, alongside muscle anabolic/catabolic signalling via immunoblotting.RESULTS: RET increased 1-RM equally in the trained leg of both groups (+23 ± 5% n-3 PUFA vs. +25 ± 5% PLA (both P < 0.01)) with no significant increase in maximum voluntary contraction (MVC) (+10 ± 6% n-3 PUFA vs. +13 ± 5% PLA). Only the n-3 PUFA group increased TFFM (3774 ± 158 g to 3961 ± 151 g n-3 PUFA (P < 0.05) vs. 3406 ± 201 g to 3561 ± 170 PLA) and type II fibre CSA (3097 ± 339 μm2 to 4329 ± 264 μm2 n-3 PUFA (P < 0.05) vs. 2520 ± 316 μm2 to 3467 ± 303 μm2 in PL) with RET. Myonuclei number increased equally in n-3 PUFA and PLA in both type I and type II fibres, with no change in SC number. N-3 PUFA had no added benefit on muscle protein synthesis (MPS), however, during weeks 4-6 of RET, absolute synthesis rates (ASR) displayed a trend to increase with n-3 PUFA only (5.6 ± 0.3 g d-1 to 7.1 ± 0.5 g d-1 n-3 PUFA (P = 0.09) vs. 5.5 ± 0.5 g d-1 to 6.5 ± 0.5 g d-1 PLA). Further, the n-3 PUFA group displayed greater 4EBP1 activation after acute RE at 6 weeks.CONCLUSION: n3-PUFA enhanced RET gains in muscle mass through type II fibre hypertrophy, with data suggesting a role for MPS rather than via SC recruitment. As such, the present study adds to a literature base illustrating the apparent enhancement of muscle hypertrophy with RET in older women fed adjuvant n3-PUFA.
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| 10. |
- Chaillou, Thomas, 1985-, et al.
(författare)
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Glutamine-stimulated in vitro hypertrophy is preserved in muscle cells from older women
- 2020
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Ingår i: Mechanisms of Ageing and Development. - : Elsevier. - 0047-6374 .- 1872-6216. ; 187
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Tidskriftsartikel (refereegranskat)abstract
- Age-related loss of muscle mass may result from reduced protein synthesis stimulation in response to anabolic stimuli, such as amino acid (AA) supplementation. The exact etiology of anabolic resistance to AA remains unclear. Therefore, the aim of this study was to investigate the anabolic response [cell size, protein synthesis and mechanistic target of rapamycin (mTOR) pathway] to the AA glutamine (a strong anabolic AA highly present in skeletal muscle) in myotubes obtained from 8 young (YW; 21-35 yrs) and 8 older (OW; 65-70 yrs) healthy women. This in vitro model of human primary myogenic cells explores the intrinsic behavior of muscle cells, while excluding potential influences of external factors. We showed that despite lower muscle mass, strength and cardiorespiratory fitness in OW compared to YW, myotube size (myotube diameter and area) and protein synthesis were not altered in OW, and glutamine-induced myotube hypertrophy and protein synthesis were preserved in OW. Apart from a lower glutamine-induced increase in P70S6 kinase phosphorylation in OW, no significant differences in other components of the mTOR pathway were observed between groups. Altogether, our data support the idea that the intrinsic capacity of muscle cells to respond to glutamine stimulation is preserved in healthy older women.
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