Determining the effect of glucagon-like peptide 1 (GLP-1) upon skeletal muscle metabolism and blood flow in older age

Age-related musculoskeletal and metabolic disorders often resulting from glucose intolerance due to age-related insulin resistance represent one of the most significant health problems in our ageing world. The incretin hormone glucagon-like peptide-1 (GLP-1) has shown to have positive effects on vascular function and glucose disposal as demonstrated by recent human and animal studies. This study, therefore, aimed to investigate whether GLP-1 can exert the same positive effect on muscle’s postprandial glucose metabolism and vascular blood flow in old age. To examine such effects, the study was conducted in a cross-over design (± GLP-1) consisting of two acute study visits with a four week ‘wash-out’ period. GLP-1 was infused in the femoral artery in overnight fasted healthy old volunteers (n=7) along with glucose and insulin clamps in combination with Octreotide and amino acids to achieve constant postprandial conditions. Leg blood flow (LBF) was measured by Doppler ultrasound, computation of rates of total body glucose metabolism (M) during the clamps was calculated by glucose infusion rates minus urinary loss of glucose minus space correction and leg glucose disposal by arterial-venous (A-V) balance technique. Our results show that the infusion of GLP-1 increased overall LBF, which was significant when a t-test was applied (P < 0.05) but not significant using a 2-way ANOVA. Significant increases (P < 0.05) were also seen in measured whole body glucose metabolism (M). However, glucose leg uptake during the GLP-1 infusion did not significantly increase. We, therefore, conclude that GLP-1 infusion in healthy old people has a significant effect on whole body postprandial glucose metabolism and vascular blood flow. However, this effect may be influenced by raised insulin concentrations and exerted possibly through an insulin-mediated mechanism and not by GLP-1 action alone. Nevertheless, GLP-1 effect could still contribute to the increased delivery of glucose to the muscle in the elderly and specifically combat the negative consequences of ageing i.e. impaired glucose uptake, vascular blood flow and age-related insulin resistance by further enhancing the action of insulin. However, further investigations are required

Prediction of protein assemblies, the next frontier: The CASP14-CAPRI experiment

We present the results for CAPRI Round 50, the fourth joint CASP-CAPRI protein assembly prediction challenge. The Round comprised a total of twelve targets, including six dimers, three trimers, and three higher-order oligomers. Four of these were easy targets, for which good structural templates were available either for the full assembly, or for the main interfaces (of the higher-order oligomers). Eight were difficult targets for which only distantly related templates were found for the individual subunits. Twenty-five CAPRI groups including eight automatic servers submitted ~1250 models per target. Twenty groups including six servers participated in the CAPRI scoring challenge submitted ~190 models per target. The accuracy of the predicted models was evaluated using the classical CAPRI criteria. The prediction performance was measured by a weighted scoring scheme that takes into account the number of models of acceptable quality or higher submitted by each group as part of their five top-ranking models. Compared to the previous CASP-CAPRI challenge, top performing groups submitted such models for a larger fraction (70–75%) of the targets in this Round, but fewer of these models were of high accuracy. Scorer groups achieved stronger performance with more groups submitting correct models for 70–80% of the targets or achieving high accuracy predictions. Servers performed less well in general, except for the MDOCKPP and LZERD servers, who performed on par with human groups. In addition to these results, major advances in methodology are discussed, providing an informative overview of where the prediction of protein assemblies currently stands.Cancer Research UK, Grant/Award Number: FC001003; Changzhou Science and Technology Bureau, Grant/Award Number: CE20200503; Department of Energy and Climate Change, Grant/Award Numbers: DE-AR001213, DE-SC0020400, DE-SC0021303; H2020 European Institute of Innovation and Technology, Grant/Award Numbers: 675728, 777536, 823830; Institut national de recherche en informatique et en automatique (INRIA), Grant/Award Number: Cordi-S; Lietuvos Mokslo Taryba, Grant/Award Numbers: S-MIP-17-60, S-MIP-21-35; Medical Research Council, Grant/Award Number: FC001003; Japan Society for the Promotion of Science KAKENHI, Grant/Award Number: JP19J00950; Ministerio de Ciencia e Innovación, Grant/Award Number: PID2019-110167RB-I00; Narodowe Centrum Nauki, Grant/Award Numbers: UMO-2017/25/B/ST4/01026, UMO-2017/26/M/ST4/00044, UMO-2017/27/B/ST4/00926; National Institute of General Medical Sciences, Grant/Award Numbers: R21GM127952, R35GM118078, RM1135136, T32GM132024; National Institutes of Health, Grant/Award Numbers: R01GM074255, R01GM078221, R01GM093123, R01GM109980, R01GM133840, R01GN123055, R01HL142301, R35GM124952, R35GM136409; National Natural Science Foundation of China, Grant/Award Number: 81603152; National Science Foundation, Grant/Award Numbers: AF1645512, CCF1943008, CMMI1825941, DBI1759277, DBI1759934, DBI1917263, DBI20036350, IIS1763246, MCB1925643; NWO, Grant/Award Number: TOP-PUNT 718.015.001; Wellcome Trust, Grant/Award Number: FC00100

Long-Term Effect of Exercise on Irisin Blood Levels—Systematic Review and Meta-Analysis

Physical exercise may activate a number of important biochemical processes in the human body. The aim of this systematic review and meta-analysis was to identify the long-term effect of physical activity on irisin blood levels. We searched PubMed, Scopus, and Web of Science for articles addressing the long-term effect of physical exercise on irisin blood levels. Fifty-nine articles were included in the final qualitative and quantitative syntheses. A statistically significant within-group effect of exercise on irisin blood levels was in 33 studies; out of them, the irisin level increased 23× and decreased 10×. The significant positive between-groups effect was found 11×. Furthermore, the meta-analysis indicated that physical exercise had a significant positive effect on irisin blood levels (SMD = 0.39 (95% CI 0.27–0.52)). Nevertheless, considerably high heterogeneity was found in all the analyses. This systematic review and meta-analysis indicate that physical exercise might increase irisin blood levels; however, the results of individual studies were considerably inconsistent, which questions the methodological detection of irisin by ELISA kits

Determining the effect of glucagon-like peptide 1 (GLP-1) upon skeletal muscle metabolism and blood flow in older age

Age-related musculoskeletal and metabolic disorders often resulting from glucose intolerance due to age-related insulin resistance represent one of the most significant health problems in our ageing world. The incretin hormone glucagon-like peptide-1 (GLP-1) has shown to have positive effects on vascular function and glucose disposal as demonstrated by recent human and animal studies. This study, therefore, aimed to investigate whether GLP-1 can exert the same positive effect on muscle’s postprandial glucose metabolism and vascular blood flow in old age. To examine such effects, the study was conducted in a cross-over design (± GLP-1) consisting of two acute study visits with a four week ‘wash-out’ period. GLP-1 was infused in the femoral artery in overnight fasted healthy old volunteers (n=7) along with glucose and insulin clamps in combination with Octreotide and amino acids to achieve constant postprandial conditions. Leg blood flow (LBF) was measured by Doppler ultrasound, computation of rates of total body glucose metabolism (M) during the clamps was calculated by glucose infusion rates minus urinary loss of glucose minus space correction and leg glucose disposal by arterial-venous (A-V) balance technique. Our results show that the infusion of GLP-1 increased overall LBF, which was significant when a t-test was applied (P < 0.05) but not significant using a 2-way ANOVA. Significant increases (P < 0.05) were also seen in measured whole body glucose metabolism (M). However, glucose leg uptake during the GLP-1 infusion did not significantly increase. We, therefore, conclude that GLP-1 infusion in healthy old people has a significant effect on whole body postprandial glucose metabolism and vascular blood flow. However, this effect may be influenced by raised insulin concentrations and exerted possibly through an insulin-mediated mechanism and not by GLP-1 action alone. Nevertheless, GLP-1 effect could still contribute to the increased delivery of glucose to the muscle in the elderly and specifically combat the negative consequences of ageing i.e. impaired glucose uptake, vascular blood flow and age-related insulin resistance by further enhancing the action of insulin. However, further investigations are required

The importance of sonographic evaluation of muscle depth and thickness prior to the 'tiny percutaneous needle biopsy'

Biopsy of human skeletal muscle tissue is a widely used method in many research studies, where 'the tiny percutaneous needle biopsy' (TPNB) is one of the relatively simplest and safest procedures currently available. By using and contrasting ultrasound images of vastus lateralis of young and elderly subjects, this work highlights further the safety aspects of TPNB and stresses the importance of prior ultrasound evaluation of muscle depth and thickness in order to prevent wrong muscle group or tissue sampling in subsequent laboratory analyses

Muscle Hypertrophy and Architectural Changes in Response to Eight-Week Neuromuscular Electrical Stimulation Training in Healthy Older People

Loss of muscle mass of the lower limbs and of the spine extensors markedly impairs locomotor ability and spine stability in old age. In this study, we investigated whether 8 w of neuromuscular electrical stimulation (NMES) improves size and architecture of the lumbar multifidus (LM) and vastus lateralis (VL) along with locomotor ability in healthy older individuals. Eight volunteers (aged 65 ≥ years) performed NMES 3 times/week. Eight sex- and age-matched individuals served as controls. Functional tests (Timed Up and Go test (TUG) and Five Times Sit-to-Stand Test (FTSST)), VL muscle architecture (muscle thickness (MT), pennation angle (PA), and fiber length (FL)), along with VL cross-sectional area (CSA) and both sides of LM were measured before and after by ultrasound. By the end of the training period, MT and CSA of VL increased by 8.6% and 11.4%, respectively. No significant increases were observed in FL and PA. LM CSA increased by 5.6% (left) and 7.1% (right). Interestingly, all VL architectural parameters significantly decreased in the control group. The combined NMES had a large significant effect on TUG (r = 0.50, p = 0.046). These results extend previous findings on the hypertrophic effects of NMES training, suggesting to be a useful mean for combating age-related sarcopenia

Feeding Your Himalayan Expedition: Nutritional Signatures and Body Composition Adaptations of Trekkers and Porters

High-altitude exposure leads to many physiological challenges, such as weight loss and dehydration. However, little attention has been posed to the role of nutrition and ethnic differences. Aiming to fulfill this gap, five Italian trekkers and seven Nepalese porters, all males, recorded their diet in diaries during a Himalayan expedition (19 days), and the average daily intake of micro and macro-nutrients were calculated. Bioimpedance analysis was performed five times during the trek; muscle ultrasound was performed before and after the expedition, only for the Italians. The Nepalese group consumed a lot of rice and only Italians consumed cheese. Water intake was slightly over 3000 g/d for both groups. Nepalese diet had a higher density of dietary fibre and lower density of riboflavin, vitamins A, K, and B12. Intake of calcium was lower than recommended levels. Body mass index, waist circumference, fat-free mass, and total body water decreased in both groups, whereas resistance (Rz) increased. Italians reactance (Xc) increased at day 9, whereas that of Nepalese occurred at days 5, 9, and 16. The cross-sectional area of the Vastus lateralis was reduced after the expedition. Specific nutritional and food-related risk factors guidance is needed for diverse expedition groups. Loss of muscle mass and balance of fluids both deserve a particular focus as concerns altitude expeditions

Feeding Your Himalayan Expedition: Nutritional Signatures and Body Composition Adaptations of Trekkers and Porters

High-altitude exposure leads to many physiological challenges, such as weight loss and dehydration. However, little attention has been posed to the role of nutrition and ethnic differences. Aiming to fulfill this gap, five Italian trekkers and seven Nepalese porters, all males, recorded their diet in diaries during a Himalayan expedition (19 days), and the average daily intake of micro and macro-nutrients were calculated. Bioimpedance analysis was performed five times during the trek; muscle ultrasound was performed before and after the expedition, only for the Italians. The Nepalese group consumed a lot of rice and only Italians consumed cheese. Water intake was slightly over 3000 g/d for both groups. Nepalese diet had a higher density of dietary fibre and lower density of riboflavin, vitamins A, K, and B12. Intake of calcium was lower than recommended levels. Body mass index, waist circumference, fat-free mass, and total body water decreased in both groups, whereas resistance (Rz) increased. Italians reactance (Xc) increased at day 9, whereas that of Nepalese occurred at days 5, 9, and 16. The cross-sectional area of the Vastus lateralis was reduced after the expedition. Specific nutritional and food-related risk factors guidance is needed for diverse expedition groups. Loss of muscle mass and balance of fluids both deserve a particular focus as concerns altitude expeditions