The muscle metabolome differs between healthy and frail older adults

Populations around the world are aging rapidly. Age-related loss of physiological functions negatively affects quality of life. A major contributor to the frailty syndrome of aging is loss of skeletal muscle. In this study we assessed the skeletal muscle biopsy metabolome of healthy young, healthy older and frail older subjects to determine the effect of age and frailty on the metabolic signature of skeletal muscle tissue. In addition, the effects of prolonged whole-body resistance-type exercise training on the muscle metabolome of older subjects were examined. The baseline metabolome was measured in muscle biopsies collected from 30 young, 66 healthy older subjects and 43 frail older subjects. Follow-up samples from frail older (24 samples) and healthy older subjects (38 samples) were collected after 6 months of prolonged resistance-type exercise training. Young subjects were included as a reference If thisgroup. Primary differences in skeletal muscle metabolite levels between young and healthy older subjects were related to mitochondrial function, muscle fiber type, and tissue turnover. Similar differences were observed when comparing frail older subjects with healthy older subjects at baseline. Prolonged resistance-type exercise training resulted in an adaptive response of amino acid metabolism, especially reflected in branched chain amino acids and genes related to tissue remodeling. The effect of exercise training on branched-chain amino acid-derived acylcarnitines in older subjects points to a downward shift in branched-chain amino acid catabolism upon training. We observed only modest correlations between muscle and plasma metabolite levels, which pleads against the use of plasma metabolites as a direct read-out of muscle metabolism and stresses the need for direct assessment of metabolites in muscle tissue biopsies

Multi-scale imaging of protein oxidation in mayonnaise

In mayonnaise, lipid and protein oxidation are closely related and the interplay between them is critical for understanding the chemical shelf-life stability of mayonnaise. This is in particular the case for comprehending the role of low-density lipoprotein (LDL) particles as a main emulsifier. Here, we monitored oxidation and the concomitant aggregation of LDLs by bright field light microscopy and cryogenic transmission electron microscopy. We further probed the formation of protein radicals and protein oxidation by imaging the accumulation of a water-soluble fluorescent spintrap and protein autofluorescence. The effect of variation of pH and addition of EDTA on accumulation of spintraps validated that protein radicals were induced by lipid radicals. We observed protein radical formation at both the oil/water droplet interface and in the continuous phase. Our data suggests two main pathways of oxidative protein radical formation in LDL particles: at the droplet interface, induced by lipid free radicals formed in oil droplets, and in the continuous phase induced by an independent LDL-specific mechanism

Effect of theobromine consumption on serum lipoprotein profiles in apparently healthy humans with low HDL-cholesterol concentrations

Scope: Theobromine is a major active compound in cocoa with allegedly beneficial effect on high-density-lipoprotein-cholesterol (HDL-CH). We have investigated the effect of theobromine (TB) consumption on the concentrations of triglyceride (TG) and cholesterol (CH) in various lipoprotein (LP) subclasses. Methods: In a randomized, double-blind, placebo-controlled, cross-over study, 44 apparently healthy women and men (age: 60 ± 6 years, BMI: 29 ± 3 kg/m2) with low baseline HDL-CH concentrations consumed a drink supplemented with 500 mg/d theobromine for 4 weeks. TG and CH concentrations in 15 LP subclasses were predicted from diffusion-edited 1H NMR spectra of fasting serum. Results: The LP phenotype of the subjects was characterized by low CH concentrations in the large HDL particles and high TG concentrations in large VLDL and chylomicron (CM) particles, which clearly differed from a LP phenotype of subjects with normal HDL-CH. TB only reduced CH concentrations in the LDL particles by 3.64 and 6.79%, but had no effect on TG and CH in any of the HDL, VLDL and CM subclasses. Conclusion: TB was not effective on HDL-CH in subjects with a LP phenotype characterized by low HDL-CH and high TG in VLDL

Difftrain: A Novel Approach to a True Spectroscopic Single-Scan Diffusion Measurement

Diffusion-ordered spectroscopy (DOSY) has gained considerable attention over the past decade as a useful tool for calculating diffusion-related parameters or in the analysis of complex (reaction) mixtures. A major drawback of the established methods are the relatively long recording times needed to acquire the spectra, excluding the monitoring of rapidly progressing reactions and (hence) measurements of less stable components. In order to overcome these shortcomings a new pulse sequence, Difftrain, has been developed. The sequence involves stimulated echo attenuation, multilow flip angle excitation, and multiple sampling of the FID during the longitudinal storage. The calculated diffusion parameters obtained by Difftrain were compared with those obtained by the established sequence BPPSTE (bipolar pulse pair stimulated echo) and were in good agreement. For systems with moderate to good signal-to-noise ratios the Difftrain building block yields significant saving in recording time (single-shot acquisition instead of acquiring n-different gradients strengths), thus opening up new applications in nonequilibrium systems and screening of compositions and/or interactions of (larger) compound arrays