| 1. |
- Bankole, Landry-Cyrille, 1977-, et al.
(författare)
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Safety and efficacy of a 6-month home-based exercise program in patients with facioscapulohumeral muscular dystrophy A randomized controlled trial
- 2016
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Ingår i: Medicine. - : Lippincott Williams & Wilkins. - 0025-7974 .- 1536-5964. ; 95:31
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Tidskriftsartikel (refereegranskat)abstract
- Background: Previous randomized controlled trials investigating exercise training programs in facioscapulohumeral muscular dystrophy (FSHD) patients are scarce and of short duration only. This study assessed the safety and efficacy of a 6-month home-ased exercise training program on fitness, muscle, and motor function in FSHD patients.Methods: Sixteen FSHD patients were randomly assigned to training (TG) and control (CG) groups (both n=8) in a home-based exercise intervention. Training consisted of cycling 3 times weekly for 35minutes (combination of strength, high-intensity interval, and low-intensity aerobic) at home for 24 weeks. Patients in CG also performed an identical training program (CTG) after 24 weeks. The primary outcome was change in peak oxygen uptake (VO2 peak) measured every 6 weeks. The principal secondary outcomes were maximal quadriceps strength (MVC) and local quadriceps endurance every 12 weeks. Other outcome measures included maximal aerobic power (MAP) and experienced fatigue every 6 weeks, 6-minute walking distance every 12 weeks, and muscle characteristics from vastus lateralis biopsies taken pre- and postintervention.Results: The compliance rate was 91% in TG. Significant improvements with training were observed in the VO2 peak (+19%, P= 0.002) and MAP by week 6 and further to week 24. Muscle endurance, MVC, and 6-minute walking distance increased and experienced fatigue decreased. Muscle fiber cross-sectional area and citrate synthase activity increased by 34% (P=0.008) and 46% (P=0.003), respectively. Dystrophic pathophysiologic patterns were not exacerbated. Similar improvements were experienced by TG and CTG.Conclusions: A combined strength and interval cycling exercise-training program compatible with patients' daily professional and social activities leads to significant functional benefits without compromising muscle tissue.
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| 2. |
- Bergens, Oscar, 1991-, et al.
(författare)
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Cardiorespiratory Fitness Does Not Offset Adiposity-Related Systemic Inflammation in Physically Active Older Women
- 2019
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : Williams & Wilkins Co.. - 0021-972X .- 1945-7197. ; 104:9, s. 4119-4126
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Tidskriftsartikel (refereegranskat)abstract
- CONTEXT: Chronic inflammation increases diabetes risk and may be exacerbated by excess adipose tissue. Whether cardiovascular fitness can offset chronic inflammation associated with excess adipose tissue in older adults is unclear.OBJECTIVE: The study aimed to examine the influence of cardiorespiratory fitness on links between adiposity and pro- and anti-inflammatory biomarkers related to metabolic risk in physically active older women.DESIGN, SETTING AND PARTICIPANTS: Cross-sectional study comprising older community-dwelling women (n = 109; age, 65-70 yr).MAIN OUTCOME: Cardiorespiratory fitness was assessed using a standardized submaximal test and participants were categorized into high and low adiposity-related metabolic risk (body mass index, waist-to-hip ratio (WHR) and total fat mass). The inflammatory biomarkers C-reactive protein (CRP), interleukin-6 (IL-6), IL-10, IL-18, adiponectin, monocyte chemoattractant protein-1 (MCP-1), and macrophage inflammatory protein (MIP-1α) were analyzed.RESULTS: Regardless of adiposity measure, women in the metabolic high-risk group had significantly (P<0.05) elevated CRP and lower adiponectin levels. Levels of IL-6 and MIP1-α were significantly elevated in the high-risk group defined by WHR and total fat mass. IL-18 level was significantly elevated in the high-risk group based on WHR only. Importantly, a high cardiorespiratory fitness level did not attenuate the detrimental links between adiposity measures and inflammation.CONCLUSIONS: Altogether, cardiorespiratory fitness does not offset the detrimental links between adiposity and several inflammatory biomarkers related to metabolic risk in physically active older women. Reducing abdominal adipose tissue in older adults should be emphasized in efforts aiming to attenuate age-related systemic inflammation and metabolic risk regardless of cardiorespiratory fitness.
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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. ; 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. |
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| 5. |
- Edholm, Peter, 1977-, et al.
(författare)
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Lower limb explosive strength capacity in elderly women : effects of resistance training and healthy diet
- 2017
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Ingår i: Journal of applied physiology. - : American Physiological Society. - 8750-7587 .- 1522-1601. ; 123:1, s. 190-196
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Tidskriftsartikel (refereegranskat)abstract
- The effects of 24 wk of resistance training combined with a healthy diet on lower limb explosive strength capacity were investigated in a population of healthy elderly women. Participants (n = 63; 67.5 ± 0.4 yr) were randomized into three groups; resistance training (RT), resistance training and healthy diet (RT-HD), and control (CON). Progressive resistance training was performed at a load of 75-85% one-repetition maximum. A major adjustment in the healthy dietary approach was an n-6/n-3 polyunsaturated fatty acid (PUFA) ratio below 2. Lower limb maximal strength, explosive force capacity during dynamic and isometric movements, whole body lean mass, and physical function were assessed. Whole body lean mass significantly increased by 1.5 ± 0.5% in RT-HD only. Isometric strength performance during knee extension as well as the performance in the five sit-to-stand and single-leg-stance tests increased similarly in RT and RT-HD. Improvements in dynamic peak power and time to reach peak power (i.e shorter time) during knee extension occurred in both RT (+15.7 ± 2.6 and -11.0 ± 3.8%, respectively) and RT-HD (+24.6 ± 2.6 and -20.3 ± 2.7%, respectively); however, changes were significantly larger in RT-HD. Similarly, changes in peak force and rate of force development during squat jump were higher in RT-HD (+58.5 ± 8.4 and +185.4 ± 32.9%, respectively) compared with RT (+35.7 ± 6.9 and +105.4 ± 22.4%, respectively). In conclusion, a healthy diet rich in n-3 PUFA can optimize the effects of resistance training on dynamic explosive strength capacity during isolated lower limb movements and multijoint exercises in healthy elderly women.NEW & NOTEWORTHY Age-related decline in lower limb explosive strength leads to impaired ability to perform daily living tasks. The present randomized controlled trial demonstrates that a healthy diet rich in n-3 polyunsaturated fatty acid (n-3 PUFA) enhances resistance training-induced gains in dynamic explosive strength capacity during isolated lower limb movements and multijoint exercises in healthy elderly women. This supports the use of strategies combining resistance training and dietary changes to mitigate the decline in explosive strength capacity in older adults.
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| 6. |
- Edholm, Peter, 1977-, et al.
(författare)
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Physical function in older adults : Impacts of past and present physical activity behaviors
- 2019
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Ingår i: Scandinavian Journal of Medicine and Science in Sports. - : John Wiley & Sons. - 0905-7188 .- 1600-0838. ; 29:3, s. 415-421
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Tidskriftsartikel (refereegranskat)abstract
- While physical activity (PA) may counteract age-related functional decline and loss of independence at old age, to what extent physical function is influenced by past or present PA behaviors is currently unclear. Therefore, the aim of the study was to examine relationships between both past and present PA behaviors and components of physical function in older women. A physical function score based on the 6-minute walk test, squat jump, and single-leg-stance balance was aggregated in 60 older women (65-70 years). Present PA behavior was assessed by accelerometry (Actigraph) and past leisure-time PA was self-reported, where times in sports-related activities and in walking were analyzed separately. Analysis of differences in physical function across tertiles of PA behaviors was adjusted by DXA-derived fat mass. Physical activity level at present age and engagements in sports-related activities before retirement age, excluding walking, were both associated (P < 0.05) to physical function. Time spent in PA of at least moderate intensity was associated with physical function (P < 0.05), whereas no corresponding relationships to either sedentary time or time in light intensity PA were observed. In conclusion, PA behaviors at present age and engagement in sports-related activities performed during adulthood are both related to physical function in older women. Being physically active at old age infers beneficial effects on physical function, even in individuals with a past or present sedentary lifestyle, which supports public health efforts aiming at increasing daily time in PA of at least moderate intensity to preserve physical function in older women.
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| 7. |
- Folkesson, Mattias, 1972-
(författare)
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Heat shock proteins in exercised human skeletal muscle
- 2018
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Exercise is considered as an important stressor accompanied by concerted molecular and cellular changes leading to adaptations at the level of skeletal muscle size and function. An important protein family produced by cells in response to stressful conditions is the heat shock proteins (HSPs). It is suggested that the different HSPs play specific roles in acute and longterm responses to exercise-induced stress. The overall aim of this thesis was to explore the expression of four different HSPs (αB-crystallin, HSP27, HSP60 and HSP70) in human skeletal muscle exposed to exercise, with a special emphasis on the role played by HSP27 in the hypertrophy of human skeletal muscle.One of the major findings was the fibre type-specific expression of HSPs in resting human skeletal muscle, including the preferential expression of HSP27 in fast type II muscle fibres. Another finding was the occurrence of training background-related differences in the expression of HSPs. Also, a cytoplasmic relocation of HSP27, occurring specifically in type II muscle fibres, was shown in response to a single bout of resistance exercise. Interestingly, there were no corresponding changes in response to an endurance exercise bout, suggesting that HSP27 may be specifically involved in the adaptations to resistance exercise. In order to test this hypothesis, an in-vitro exercise model based on the electrical pulse stimulation (EPS) of muscle cells was developed. The EPS protocol, including an 8 h restitution period, induced a significant hypertrophy of muscle cells together with molecular changes similar to those previously described in response to exercise in humans. The role of HSP27 in the hypertrophy of human muscle cells was examined through the downregulation of HSP27. Based on data from morphological and microarray analyses, findings indicate that HSP27 is not mandatory for the hypertrophy of human muscle cells. Overall, the present thesis clarified the expression of different HSPs in human skeletal muscle and provided an in-vitro-based approach for the elucidation of the exact role played by HSPs in the adaptations of human skeletal muscle to exercise.
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| 8. |
- Gharahdaghi, Nima, et al.
(författare)
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Testosterone therapy induces molecular programming augmenting physiological adaptations to resistance exercise in older men
- 2019
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Ingår i: Journal of Cachexia, Sarcopenia and Muscle. - : John Wiley & Sons. - 2190-5991 .- 2190-6009. ; 10:6, s. 1276-1294
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Tidskriftsartikel (refereegranskat)abstract
- Background: The andropause is associated with declines in serum testosterone (T), loss of muscle mass (sarcopenia), and frailty. Two major interventions purported to offset sarcopenia are anabolic steroid therapies and resistance exercise training (RET). Nonetheless, the efficacy and physiological and molecular impacts of T therapy adjuvant to short-term RET remain poorly defined.Methods: Eighteen non-hypogonadal healthy older men, 65-75 years, were assigned in a random double-blinded fashion to receive, biweekly, either placebo (P, saline, n = 9) or T (Sustanon 250 mg, n = 9) injections over 6 week whole-body RET (three sets of 8-10 repetitions at 80% one-repetition maximum). Subjects underwent dual-energy X-ray absorptiometry, ultrasound of vastus lateralis (VL) muscle architecture, and knee extensor isometric muscle force tests; VL muscle biopsies were taken to quantify myogenic/anabolic gene expression, anabolic signalling, muscle protein synthesis (D2O), and breakdown (extrapolated).Results: Testosterone adjuvant to RET augmented total fat-free mass (P=0.007), legs fat-free mass (P=0.02), and appendicular fat-free mass (P=0.001) gains while decreasing total fat mass (P=0.02). Augmentations in VL muscle thickness, fascicle length, and quadriceps cross-section area with RET occured to a greater extent in T (P < 0.05). Sum strength (P=0.0009) and maximal voluntary contract (e.g. knee extension at 70 degrees) (P=0.002) increased significantly more in the T group. Mechanistically, both muscle protein synthesis rates (T: 2.13 +/- 0.21%center dot day(-1) vs. P: 1.34 +/- 0.13%center dot day(-1), P=0.0009) and absolute breakdown rates (T: 140.2 +/- 15.8 g center dot day(-1) vs. P: 90.2 +/- 11.7 g center dot day(-1), P=0.02) were elevated with T therapy, which led to higher net turnover and protein accretion in the T group (T: 8.3 +/- 1.4 g center dot day (-1) vs. P: 1.9 +/- 1.2 g center dot day (-1), P=0.004). Increases in ribosomal biogenesis (RNA:DNA ratio); mRNA expression relating to T metabolism (androgen receptor: 1.4-fold; Srd5a1: 1.6-fold; AKR1C3: 2.1-fold; and HSD17 beta 3: two-fold); insulin-like growth factor (IGF)-1 signalling [IGF-1Ea (3.5-fold) and IGF-1Ec (three-fold)] and myogenic regulatory factors; and the activity of anabolic signalling (e.g. mTOR, AKT, and RPS6; P < 0.05) were all up-regulated with T therapy. Only T up-regulated mitochondrial citrate synthase activity (P=0.03) and transcription factor A (1.41 +/- 0.2-fold, P=0.0002), in addition to peroxisome proliferator-activated receptor-gamma co-activator 1-alpha mRNA (1.19 +/- 0.21-fold, P=0.037).Conclusions: Administration of T adjuvant to RET enhanced skeletal muscle mass and performance, while up-regulating myogenic gene programming, myocellular translational efficiency and capacity, collectively resulting in higher protein turnover, and net protein accretion. T coupled with RET is an effective short-term intervention to improve muscle mass/function in older non-hypogonadal men.
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| 9. |
- Harandi, Vahid M., 1985-
(författare)
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A Muscle Perspective on the Pathophysiology of Amyotrophic Lateral Sclerosis : Differences between extraocular and limb muscles
- 2016
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: Amyotrophic lateral sclerosis (ALS) is a late-onset progressive neurodegenerative disorder. ALS has been traditionally believed to be primarily a motor neuron disease. However, accumulating data indicate that loss of contact between the axons and the muscle fibres occurs early; long before the death of motor neurons and that muscle fibres may initiate motor neuron degeneration. Thus, the view of ALS is changing focus from motor neurons alone to also include the muscle fibres and the neuromuscular junctions (NMJs). While skeletal muscles are affected in ALS, oculomotor disturbances are not dominant features of this disease and extraocular muscles (EOMs) are far less affected than limb muscles. Why oculomotor neurons and EOMs are capable to be more resistant in the pathogenetic process of ALS is still unknown.The overall goal of this thesis is to explore the pathophysiology of ALS from a muscle perspective and in particular study the expression and distribution of key neurotrophic factors (NTFs) and Wnt proteins in EOMs and limb muscles from ALS donors and from SOD1G93A transgenic mice. Comparisons were made with age-matched controls to distinguish between changes related to ALS and to ageing.Results: Brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF), neurotrophin-3 (NT-3) and neurotrophin-4/5 (NT-4) were present in EOMs and limb muscles at both mRNA and protein levels in control mice. The mRNA levels of BDNF, NT-3 and NT-4 were significantly lower in EOMs than in limb muscles of early and/or late control mice, indicating an intrinsic difference in NTFs expression between EOMs and limb muscles. qRT-PCR analysis showed significantly upregulated mRNA levels of NT-3 and GDNF in EOMs but significantly downregulated mRNA levels of NT-4 in limb muscles from SOD1G93A transgenic mice at early stage. The NTFs were detected immunohistochemically in NMJs, nerve axons and muscle fibres. The expression of BDNF, GDNF and NT-4 on NMJs of limb muscles, but not of EOMs, was significantly decreased in terminal stage ALS animals as compared to the limb muscles of the age-matched controls. In contrast, NTFs expression in intramuscular nerve axons did not present significant changes in either muscle group of early or late ALS mice. NTFs, especially BDNF and NT-4 were upregulated in some small-sized muscle fibres in limb muscles of late stage ALS mice. All the four Wnt isoforms, Wnt1, Wnt3a, Wnt5a and Wnt7a were detected in most axon profiles in all human EOMs with ALS, whereas significantly fewer axon profiles were positive in the human limb muscles except for Wnt5a. Similar differential patterns were found in myofibres, except for Wnt7a, where its expression was elevated within sarcolemma of limb muscle fibres. β-catenin, a marker of the canonical Wnt pathway was activated in a subset of myofibres in the EOMs and limb muscle in all ALS patients. In the SOD1G93A mouse, all four Wnt isoforms were significantly decreased in the NMJs at the terminal stage compared to age matched controls.Conclusions: There were clear differences in NTF and Wnt expression patterns between EOM and limb muscle, suggesting that they may play a role in the distinct susceptibility of these two muscle groups to ALS. In particular, the early upregulation of GDNF and NT-3 in the EOMs might play a role in the preservation of the EOMs in ALS. Further studies are needed to determine whether these proteins and the pathways they control may be have a future potential as protecting agents for other muscles.
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| 10. |
- Hosford-Donovan, Adrian, 1983-, et al.
(författare)
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Observational and mechanistic links between C-reactive protein and blood pressure in elderly women
- 2016
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Ingår i: Maturitas. - Clare, Ireland : Elsevier. - 0378-5122 .- 1873-4111. ; 89, s. 52-57
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Tidskriftsartikel (refereegranskat)abstract
- It is hypothesized that chronic systemic inflammation contributes to the age-related decline in cardiovascular function. The aim of the present study was to combine an assessment of the relationship between the serum level of C-reactive protein (CRP) and systolic and diastolic blood pressure in 108 elderly women (65 and 70 years) with an in-vitro exploration of the effects of CRP on the proliferative and angiogenic potential of endothelial cells exposed to serum in elderly women. Based on the median CRP level in our population, LowCRP (CRP<1.3mg/L) and HighCRP (>1.3mg/L) groups were identified. Body mass index, waist circumference, systolic blood pressure (SBP) and diastolic blood pressure (DBP) were significantly higher in the HighCRP group than in the LowCRP group (p<0.05). The influence of CRP on SBP and DBP remained significant after adjustments for BMI and use of antihypertensive medication (p<0.05). When adjusting for waist circumference the observed influence of CRP on SPB was attenuated (p=0.062). We next evaluated the ability to form capillary tubes (angiogenesis assay) and the proliferation rate of endothelial cells exposed to the sera of elderly women. Increased serum CRP levels were associated with an increased doubling time of endothelial cells (R(2)=0.39; p<0.05) and decreased capillary tube length (R(2)=0.30; p<0.05), indicating a reduction in the proliferation rate of endothelial cells and angiogenic potential. In conclusion, chronic inflammation influences blood pressure in elderly women and compromises endothelial cell function, thus contributing to the age-related decline in vascular health.
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