Muscle Quality is More Impaired in Sarcopenic Patients With Chronic Obstructive Pulmonary Disease

BACKGROUND: Quadriceps muscle fiber atrophy and a loss of oxidative type I muscle fibers and mitochondrial content often occur in chronic obstructive pulmonary disease (COPD), which adversely affects exercise performance. Sarcopenia is an age-related syndrome characterized by wasting and weakness of muscle mass. We recently showed in a large cohort of patients that COPD-related sarcopenia, in particular in male patients, was not only associated with impaired quadriceps muscle strength but also with decreased exercise performance endurance, which could imply involvement of altered muscle fiber type composition. Hence, we hypothesized that both the fiber atrophy and loss of oxidative muscle fibers are more pronounced in sarcopenic compared with nonsarcopenic patients with COPD. OBJECTIVE: The objective of this study was to investigate quadriceps muscle fiber-type characteristics in relation to presence of sarcopenia in patients with COPD and in healthy age-matched controls. DESIGN: For this retrospective cross-sectional study, body composition (assessed by dual-energy x-ray absorptiometry) and quadriceps muscle biopsy (fiber type distribution and sizes) data were collected from 45 patients with COPDs (aged 42-77 years) and 52 healthy controls (aged 50-77 years). Sarcopenia was based on assessment of appendicular skeletal muscle mass index. RESULTS: Sarcopenia was found in 5.8% of healthy controls and in 31.1% of patients with COPD (P < .01). The proportion of oxidative type I fibers and size of type IIx muscle fibers were decreased in patients with COPD, and the sarcopenic subgroup showed a further decreased proportion as well as a lower size of type I fibers. CONCLUSIONS: Type I muscle fiber proportion is lower in sarcopenic compared with nonsarcopenic patients with COPD. Longitudinal studies may elucidate if the loss of muscle oxidative phenotype drives or accelerates the process of muscle wasting

Targeting of anionic membrane species by lanthanide(III) complexes: towards improved MRI contrast agents for apoptosis

No abstract available

Consequences of late-stage non-small cell lung cancer cachexia on muscle metabolic processes

Introduction: Loss of muscle is common in patients with advanced non-small cell lung cancer (NSCLC), and contributes to the high morbidity and mortality of this group. The exact mechanisms behind the loss of muscle are unclear. Patients and methods: To investigate this, 4 patients with stage IV NSCLC meeting the clinical definitions for sarcopenia and cachexia were recruited, along with 4 age-matched healthy volunteers. Following an overnight fast, biopsies were obtained from the vastus lateralis and key components associated with inflammation and the control of muscle protein, carbohydrate and fat metabolism assessed. Results: Compared to healthy volunteers, significant increases in mRNA levels for interleukin-6 and NFκB signalling were observed in NSCLC patients along with lower intramyocellular lipid content in slow-twitch fibres. While a significant decrease in phosphorylation of mTOR signalling protein 4E-BP1 (Ser65) was observed along with a trend towards reduced p70 S6K (Thr389) phosphorylation (P=0.06), there was no difference between groups for mRNA levels of MAFbx and MuRF1, chymotrypsin-like activity of the proteasome, or protein levels of multiple proteasome subunits. Moreover, despite decreases in intramyocellular lipid content, no robust changes in mRNA levels for key proteins involved in insulin signalling, glycolysis, oxidative metabolism or fat metabolism were observed. Conclusions: These findings suggest that an examination of the contribution of suppressed mTOR signalling in the loss of muscle mass in late-stage NSCLC patients is warranted and reinforces our need to understand the potential contribution of impaired fat metabolism and muscle protein synthesis in the aetiology of cancer cachexia

Impacts of High-Protein Oral Nutritional Supplements Among Malnourished Men and Women with Sarcopenia: A Multicenter, Randomized, Double-Blinded, Controlled Trial.

BACKGROUND: Recent evidence suggests that nutritional interventions may improve muscle outcomes in malnutrition and sarcopenia. OBJECTIVES: We evaluated the effects of 2 high-quality oral nutritional supplements (ONS) differing in amount and type of key nutrients in older adult men and women. DESIGN: A multicenter, randomized, double-blinded, controlled clinical trial. PARTICIPANTS: Malnourished and sarcopenic men and women, 65 years and older (n = 330). INTERVENTION: A 24-week intervention period with 2 energy-rich (330 kcal) ONS treatment groups: Control ONS (CONS, 14 g protein; 147 IU vitamin D3) versus Experimental ONS (EONS, 20 g protein; 499 IU vitamin D3; 1.5 g CaHMB) taken twice daily. Both ONS also contained other vitamins, minerals, and nutrients in varying amounts. MEASUREMENTS: Isokinetic peak torque (PT, Nm) leg strength, grip strength (kg), and gait speed (m·s-1) were assessed at baseline and 12 and 24 weeks. Left and right leg muscle mass (LMM, kg) were assessed by dual-energy x-ray absorptiometry (DXA). Muscle quality (MQ) was leg strength expressed relative to the tested LMM (Nm·kg-1). Subgroup analyses were performed: severe sarcopenia (low skeletal mass index, low grip strength [ CONS, P = .032) in those with normal grip strength. There were no treatment differences based on sarcopenic severity for either grip strength or gait speed. CONCLUSION: ONS improved strength outcomes in malnourished older adults with sarcopenia. In those with mild-moderate sarcopenia, but not severe sarcopenia, consumption of the EONS improved leg muscle strength and quality compared with the standard CONS

A Putative Plant Aminophospholipid Flippase, the Arabidopsis P4 ATPase ALA1, Localizes to the Plasma Membrane following Association with a β-Subunit

Plasma membranes in eukaryotic cells display asymmetric lipid distributions with aminophospholipids concentrated in the inner leaflet and sphingolipids in the outer leaflet. This unequal distribution of lipids between leaflets is, amongst several proposed functions, hypothesized to be a prerequisite for endocytosis. P4 ATPases, belonging to the P-type ATPase superfamily of pumps, are involved in establishing lipid asymmetry across plasma membranes, but P4 ATPases have not been identified in plant plasma membranes. Here we report that the plant P4 ATPase ALA1, which previously has been connected with cold tolerance of Arabidopsis thaliana, is targeted to the plasma membrane and does so following association in the endoplasmic reticulum with an ALIS protein β-subunit