scholarly journals Nicotinamide riboside augments the human skeletal muscle NAD+ metabolome and induces transcriptomic and anti-inflammatory signatures in aged subjects: a placebo-controlled, randomized trial

2019 ◽  
Author(s):  
Yasir S Elhassan ◽  
Katarina Kluckova ◽  
Rachel S Fletcher ◽  
Mark Schmidt ◽  
Antje Garten ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Metabolic Stress ◽  
Human Muscle ◽  
Resonance Spectroscopy ◽  
Metabolic Dysfunction ◽  
Double Blind ◽  
Chronological Aging ◽  
Nicotinamide Riboside ◽  
Anti Inflammatory ◽  
Aged Subjects

SUMMARYNAD+ is modulated by conditions of metabolic stress and has been reported to decline with aging, but human data are sparse. Nicotinamide riboside (NR) supplementation ameliorates metabolic dysfunction in rodents. We aimed to establish whether oral NR supplementation in aged participants can increase the skeletal muscle NAD+ metabolome, and questioned if tissue NAD+ levels are depressed with aging. We supplemented 12 aged men with NR 1g per day for 21-days in a placebo-controlled, randomized, double-blind, crossover trial. Targeted metabolomics showed that NR elevated the muscle NAD+ metabolome, evident by increased nicotinic acid adenine dinucleotide and nicotinamide clearance products. Muscle RNA sequencing revealed NR-mediated downregulation of energy metabolism and mitochondria pathways. NR also depressed levels of circulating inflammatory cytokines. In an additional study, 31P magnetic resonance spectroscopy-based NAD+ measurement in muscle and brain showed no difference between young and aged individuals. Our data establish that oral NR is available to aged human muscle and identify anti-inflammatory effects of NR, while suggesting that NAD+ decline is not associated with chronological aging per se in human muscle or brain.

scholarly journals Normalized metabolic stress for31P-MR spectroscopy studies of human skeletal muscle: MVC vs. muscle volume

1997 ◽  
Vol 83 (3) ◽  
pp. 875-883 ◽  
Author(s):  
M. D. Fowler ◽  
T. W. Ryschon ◽  
R. E. Wysong ◽  
C. A. Combs ◽  
R. S. Balaban
Keyword(s):  
Skeletal Muscle ◽  
Power Output ◽  
Mr Spectroscopy ◽  
Human Skeletal Muscle ◽  
Plantar Flexion ◽  
Metabolic Stress ◽  
Muscle Volume ◽  
Resonance Spectroscopy ◽  
Plantar Flexor ◽  
Spectroscopy Studies

Fowler, M. D., T. W. Ryschon, R. E. Wysong, C. A. Combs, and R. S. Balaban. Normalized metabolic stress for31P-MR spectroscopy studies of human skeletal muscle: MVC vs. muscle volume. J. Appl. Physiol. 83(3): 875–883, 1997.—A critical requirement of submaximal exercise tests is the comparability of workload and associated metabolic stress between subjects. In this study, 31P-magnetic resonance spectroscopy was used to estimate metabolic strain in the soleus muscle during dynamic, submaximal plantar flexion in which target torque was 10 and 15% of a maximal voluntary contraction (MVC). In 10 healthy, normally active adults, (PCr + Pi)/PCr, where PCr is phosphocreatine, was highly correlated with power output normalized to the volume of muscle in the plantar flexor compartment ( r = 0.89, P < 0.001). The same variable was also correlated, although less strongly ( r = 0.78, P < 0.001), with power normalized to plantar flexor cross-sectional area. These findings suggest that comparable levels of metabolic strain can be obtained in subjects of different size when the power output, or stress, for dynamic plantar flexion is selected as a function of plantar flexor muscle volume. In contrast, selecting power output as a function of MVC resulted in a positive linear relationship between (PCr + Pi)/PCr and the torque produced, indicating that metabolic strain was increasing rather than achieving constancy as a function of MVC. These findings provide new insight into the design of dynamic muscle contraction protocols aimed at detecting metabolic differences between subjects of different body size but having similar blood flow capacity and mitochondrial volume per unit of muscle.

scholarly journals Nicotinamide Riboside Augments the Aged Human Skeletal Muscle NAD+ Metabolome and Induces Transcriptomic and Anti-inflammatory Signatures

Cell Reports ◽  
2019 ◽  
Vol 28 (7) ◽  
pp. 1717-1728.e6 ◽  
Author(s):  
Yasir S. Elhassan ◽  
Katarina Kluckova ◽  
Rachel S. Fletcher ◽  
Mark S. Schmidt ◽  
Antje Garten ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Human Skeletal Muscle ◽  
Nicotinamide Riboside ◽  
Anti Inflammatory

Carnosine loading and washout in human skeletal muscles

2009 ◽  
Vol 106 (3) ◽  
pp. 837-842 ◽  
Author(s):  
Audrey Baguet ◽  
Harmen Reyngoudt ◽  
Andries Pottier ◽  
Inge Everaert ◽  
Stefanie Callens ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Skeletal Muscles ◽  
Metabolic Regulation ◽  
Fiber Type ◽  
Resonance Spectroscopy ◽  
Double Blind Study ◽  
Crossover Designs ◽  
Muscle Carnosine ◽  
Double Blind ◽  
Human Skeletal Muscles

Carnosine (β-alanyl-l-histidine) is present in high concentrations in human skeletal muscles. The oral ingestion of β-alanine, the rate-limiting precursor in carnosine synthesis, has been shown to elevate the muscle carnosine content both in trained and untrained humans. Little human data exist about the dynamics of the muscle carnosine content, its metabolic regulation, and its dependence on muscle fiber type. The present study aimed to investigate in three skeletal muscle types the supplementation-induced amplitude of carnosine synthesis and its subsequent elimination on cessation of supplementation (washout). Fifteen untrained males participated in a placebo-controlled double-blind study. They were supplemented for 5–6 wk with either 4.8 g/day β-alanine or placebo. Muscle carnosine was quantified in soleus, tibialis anterior, and medial head of the gastrocnemius by proton magnetic resonance spectroscopy (MRS), before and after supplementation and 3 and 9 wk into washout. The β-alanine supplementation significantly increased the carnosine content in soleus by 39%, in tibialis by 27%, and in gastrocnemius by 23% and declined postsupplementation at a rate of 2–4%/wk. Average muscle carnosine remained increased compared with baseline at 3 wk of washout (only one-third of the supplementation-induced increase had disappeared) and returned to baseline values within 9 wk at group level. Following subdivision into high responders (+55%) and low responders (+15%), washout period was 15 and 6 wk, respectively. In the placebo group, carnosine remained relatively constant with variation coefficients of 9–15% over a 3-mo period. It can be concluded that carnosine is a stable compound in human skeletal muscle, confirming the absence of carnosinase in myocytes. The present study shows that washout periods for crossover designs in supplementation studies for muscle metabolites may sometimes require months rather than weeks.

Therapeutic Approaches to Alzheimer’s Type of Dementia: A Focus on FGF21 Mediated Neuroprotection

2019 ◽  
Vol 25 (23) ◽  
pp. 2555-2568 ◽  
Author(s):  
Rajeev Taliyan ◽  
Sarathlal K. Chandran ◽  
Violina Kakoty
Keyword(s):  
Diabetes Mellitus ◽  
Protein Trafficking ◽  
Metabolic Stress ◽  
Insulin Receptors ◽  
Metabolic Dysfunction ◽  
Beneficial Effects ◽  
Glucose And Lipid Metabolism ◽  
Endocrine Hormone ◽  
Metabolic Conditions ◽  
The Brain

Neurodegenerative disorders are the most devastating disorder of the nervous system. The pathological basis of neurodegeneration is linked with dysfunctional protein trafficking, mitochondrial stress, environmental factors and aging. With the identification of insulin and insulin receptors in some parts of the brain, it has become evident that certain metabolic conditions associated with insulin dysfunction like Type 2 diabetes mellitus (T2DM), dyslipidemia, obesity etc., are also known to contribute to neurodegeneration mainly Alzheimer’s Disease (AD). Recently, a member of the fibroblast growth factor (FGF) superfamily, FGF21 has proved tremendous efficacy in diseases like diabetes mellitus, obesity and insulin resistance (IR). Increased levels of FGF21 have been reported to exert multiple beneficial effects in metabolic syndrome. FGF21 receptors are present in certain areas of the brain involved in learning and memory. However, despite extensive research, its function as a neuroprotectant in AD remains elusive. FGF21 is a circulating endocrine hormone which is mainly secreted by the liver primarily in fasting conditions. FGF21 exerts its effects after binding to FGFR1 and co-receptor, β-klotho (KLB). It is involved in regulating energy via glucose and lipid metabolism. It is believed that aberrant FGF21 signalling might account for various anomalies like neurodegeneration, cancer, metabolic dysfunction etc. Hence, this review will majorly focus on FGF21 role as a neuroprotectant and potential metabolic regulator. Moreover, we will also review its potential as an emerging candidate for combating metabolic stress induced neurodegenerative abnormalities.

Frühgeborene unter maschineller Beatmung: Immunmodulatorischer Effekt der präventiven Gabe von Azithromycin

2020 ◽  
pp. 1-3
Author(s):  
Maximilian Jorczyk
Keyword(s):  
Very Low Birth Weight ◽  
Controlled Trial ◽  
Preterm Neonates ◽  
Double Blind ◽  
Mechanically Ventilated ◽  
Before And After ◽  
Anti Inflammatory ◽  
To Receive ◽  
Therapeutic Possibilities ◽  
Inflammatory Effect

<b>Introduction:</b> Macrolides have anti-inflammatory and immunomodulatory properties that give this class of antibiotics a role that differs from its classical use as an antibiotic, which opens new therapeutic possibilities. <b>Objective:</b> The aim of this study was to evaluate the anti-inflammatory effect of azithromycin in preventing mechanical ventilation (MV)-induced lung injury in very-low-birth-weight preterm neonates. <b>Methods:</b> This is a randomized, double-blind, placebo-controlled trial of preterm neonates who received invasive MV within 72 h of birth. Patients were randomized to receive intravenous azithromycin (at a dose of 10/mg/kg/day for 5 days) or placebo (0.9% saline) within 12 h of the start of MV. Two blood samples were collected (before and after intervention) for measurement of interleukins (ILs) and PCR for <i>Ureaplasma</i>. Patients were followed up throughout the hospital stay for the outcomes of death and bronchopulmonary dysplasia defined as need for oxygen for a period of ≥28 days of life (registered at ClinicalTrials.gov, No. NCT03485703). <b>Results:</b> Forty patients were analyzed in the azithromycin group and 40 in the placebo group. Five days after the last dose, serum IL-2 and IL-8 levels dropped significantly in the azithromycin group. There was a significant reduction in the incidence of death and O<sub>2</sub> dependency at 28 days/death in azithromycin-treated patients regardless of the detection of <i>Ureaplasma</i> in blood. <b>Conclusions:</b> Azithromycin has anti-inflammatory effects, with a decrease in cytokines after 5 days of use and a reduction in death and O<sub>2</sub> dependency at 28 days/death in mechanically ventilated preterm neonates.

scholarly journals Global Deletion of 11β-HSD1 Prevents Muscle Wasting Associated with Glucocorticoid Therapy in Polyarthritis

2021 ◽  
Vol 22 (15) ◽  
pp. 7828
Author(s):  
Justine M. Webster ◽  
Michael S. Sagmeister ◽  
Chloe G. Fenton ◽  
Alex P. Seabright ◽  
Yu-Chiang Lai ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Skeletal Muscle ◽  
Chronic Inflammation ◽  
Muscle Atrophy ◽  
Muscle Wasting ◽  
Ex Vivo ◽  
Glucocorticoid Therapy ◽  
Knock Out ◽  
Fiber Size ◽  
Anti Inflammatory

Glucocorticoids provide indispensable anti-inflammatory therapies. However, metabolic adverse effects including muscle wasting restrict their use. The enzyme 11beta-hydroxysteroid dehydrogenase type 1 (11β-HSD1) modulates peripheral glucocorticoid responses through pre-receptor metabolism. This study investigates how 11β-HSD1 influences skeletal muscle responses to glucocorticoid therapy for chronic inflammation. We assessed human skeletal muscle biopsies from patients with rheumatoid arthritis and osteoarthritis for 11β-HSD1 activity ex vivo. Using the TNF-α-transgenic mouse model (TNF-tg) of chronic inflammation, we examined the effects of corticosterone treatment and 11β-HSD1 global knock-out (11βKO) on skeletal muscle, measuring anti-inflammatory gene expression, muscle weights, fiber size distribution, and catabolic pathways. Muscle 11β-HSD1 activity was elevated in patients with rheumatoid arthritis and correlated with inflammation markers. In murine skeletal muscle, glucocorticoid administration suppressed IL6 expression in TNF-tg mice but not in TNF-tg11βKO mice. TNF-tg mice exhibited reductions in muscle weight and fiber size with glucocorticoid therapy. In contrast, TNF-tg11βKO mice were protected against glucocorticoid-induced muscle atrophy. Glucocorticoid-mediated activation of catabolic mediators (FoxO1, Trim63) was also diminished in TNF-tg11βKO compared to TNF-tg mice. In summary, 11β-HSD1 knock-out prevents muscle atrophy associated with glucocorticoid therapy in a model of chronic inflammation. Targeting 11β-HSD1 may offer a strategy to refine the safety of glucocorticoids.

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