Age-Associated Impairments in Mitochondrial ADP Sensitivity Contribute to Redox Stress in Senescent Human Skeletal Muscle.

This is the final version of the article. Available from Elsevier (Cell Press) via the DOI in this record.It remains unknown if mitochondrial bioenergetics are altered with aging in humans. We established an in vitro method to simultaneously determine mitochondrial respiration and H2O2emission in skeletal muscle tissue across a range of biologically relevant ADP concentrations. Using this approach, we provide evidence that, although the capacity for mitochondrial H2O2emission is not increased with aging, mitochondrial ADP sensitivity is impaired. This resulted in an increase in mitochondrial H2O2and the fraction of electron leak to H2O2, in the presence of virtually all ADP concentrations examined. Moreover, although prolonged resistance training in older individuals increased muscle mass, strength, and maximal mitochondrial respiration, exercise training did not alter H2O2emission rates in the presence of ADP, the fraction of electron leak to H2O2, or the redox state of the muscle. These data establish that a reduction in mitochondrial ADP sensitivity increases mitochondrial H2O2emission and contributes to age-associated redox stress.This work was funded by the Natural Sciences and Engineering Research Council of Canada (03656) and TI Food and Nutrition, a public-private partnership on precompetitive research in food and nutrition

Reproducible kk-means clustering in galaxy feature data from the GAMA survey

A fundamental bimodality of galaxies in the local Universe is apparent in many of the features used to describe them. Multiple sub-populations exist within this framework, each representing galaxies following distinct evolutionary pathways. Accurately identifying and characterising these sub-populations requires that a large number of galaxy features be analysed simultaneously. Future galaxy surveys such as LSST and Euclid will yield data volumes for which traditional approaches to galaxy classification will become unfeasible. To address this, we apply a robust $k$-means unsupervised clustering method to feature data derived from a sample of 7338 local-Universe galaxies selected from the Galaxy And Mass Assembly (GAMA) survey. This allows us to partition our sample into $k$ clusters without the need for training on pre-labelled data, facilitating a full census of our high dimensionality feature space and guarding against stochastic effects. We find that the local galaxy population natively splits into $2$, $3$, $5$ and a maximum of $6$ sub-populations, with each corresponding to a distinct ongoing evolutionary mechanism. Notably, the impact of the local environment appears strongly linked with the evolution of low-mass ($M_{*} < 10^{10}$ M$_{\odot}$) galaxies, with more massive systems appearing to evolve more passively from the blue cloud onto the red sequence. With a typical run time of $\sim3$ minutes per value of $k$ for our galaxy sample, we show how $k$-means unsupervised clustering is an ideal tool for future analysis of large extragalactic datasets, being scalable, adaptable, and providing crucial insight into the fundamental properties of the local galaxy population

Intermittent versus continuous enteral nutrition attenuates increases in insulin and leptin during short-term bed rest

This is the final version. Available on open access from Springer via the DOI in this recordPurpose: To compare endocrine responses to intermittent vs continuous enteral nutrition provision during short-term bed rest. Methods: Twenty healthy men underwent 7 days of bed rest, during which they were randomized to receive enteral nutrition (47%E as carbohydrate, 34%E as fat, 16%E as protein and 3%E as fibre) in a continuous (CONTINUOUS; n = 10; 24 h day−1 at a constant rate) or intermittent (INTERMITTENT; n = 10; as 4 meals per day separated by 5 h) pattern. Daily plasma samples were taken every morning to assess metabolite/hormone concentrations. Results: During bed rest, plasma leptin concentrations were elevated to a lesser extent with INTERMITTENT vs CONTINUOUS (iAUC: 0.42 ± 0.38 vs 0.95 ± 0.48 nmol L−1, respectively; P = 0.014) as were insulin concentrations (interaction effect, P < 0.001) which reached a peak of 369 ± 225 pmol L−1 in CONTINUOUS, compared to 94 ± 38 pmol L−1 in INTERMITTENT (P = 0.001). Changes in glucose infusion rate were positively correlated with changes in fasting plasma GLP-1 concentrations (r = 0.44, P = 0.049). Conclusion: Intermittent enteral nutrition attenuates the progressive rise in plasma leptin and insulinemia seen with continuous feeding during bed rest, suggesting that continuous feeding increases insulin requirements to maintain euglycemia. This raises the possibility that hepatic insulin sensitivity is impaired to a greater extent with continuous versus intermittent feeding during bed rest. To attenuate endocrine and metabolic changes with enteral feeding, an intermittent feeding strategy may, therefore, be preferable to continuous provision of nutrition. This trial was registered on clinicaltrials.gov as NCT02521025.University of Bat

Endurance-Type Exercise Increases Bulk and Individual Mitochondrial Protein Synthesis Rates in Rats.

Physical activity increases muscle protein synthesis rates. However, the impact of exercise on the coordinated up- and/or downregulation of individual protein synthesis rates in skeletal muscle tissue remains unclear. The authors assessed the impact of exercise on mixed muscle, myofibrillar, and mitochondrial protein synthesis rates as well as individual protein synthesis rates in vivo in rats. Adult Lewis rats either remained sedentary (n = 3) or had access to a running wheel (n = 3) for the last 2 weeks of a 3-week experimental period. Deuterated water was injected and subsequently administered in drinking water over the experimental period. Blood and soleus muscle were collected and used to assess bulk mixed muscle, myofibrillar, and mitochondrial protein synthesis rates using gas chromatography-mass spectrometry and individual muscle protein synthesis rates using liquid chromatography-mass spectrometry (i.e., dynamic proteomic profiling). Wheel running resulted in greater myofibrillar (3.94 ± 0.26 vs. 3.03 ± 0.15%/day; p < .01) and mitochondrial (4.64 ± 0.24 vs. 3.97 ± 0.26%/day; p < .05), but not mixed muscle (2.64 ± 0.96 vs. 2.38 ± 0.62%/day; p = .71) protein synthesis rates, when compared with the sedentary condition. Exercise impacted the synthesis rates of 80 proteins, with the difference from the sedentary condition ranging between -64% and +420%. Significantly greater synthesis rates were detected for F1-ATP synthase, ATP synthase subunit alpha, hemoglobin, myosin light chain-6, and synaptopodin-2 (p < .05). The skeletal muscle protein adaptive response to endurance-type exercise involves upregulation of mitochondrial protein synthesis rates, but it is highly coordinated as reflected by the up- and downregulation of various individual proteins across different bulk subcellular protein fractions

Dietary feeding pattern does not modulate the loss of muscle mass or the decline in metabolic health during short-term bed rest

This is the author accepted manuscript. The final version is available from the American Physiological Society via the DOI in this record.Short periods of bed rest lead to the loss of muscle mass and quality. It has been speculated that dietary feeding pattern may impact upon muscle protein synthesis rates and, therefore, modulate the loss of muscle mass and quality. We subjected 20 healthy men (age: 25±1 y, BMI: 23.8±0.8 kg·m-2) to one week of strict bed rest with intermittent (4 meals/day) or continuous (24 h/day) enteral tube feeding. Participants consumed deuterium oxide for 7 days prior to bed rest and throughout the 7-day bed rest period. Prior to and immediately after bed rest, lean body mass (DXA), quadriceps cross-sectional area (CSA; CT), maximal oxygen uptake capacity (VO2peak), and whole-body insulin sensitivity (hyperinsulinaemic-euglycaemic clamp) were assessed. Muscle biopsies were collected 7 days prior to, 1 day prior to, and immediately after bed rest to assess muscle tracer incorporation. Bed rest resulted in 0.3±0.3 vs 0.7±0.4 kg lean tissue loss and a 1.1±0.6 vs 0.8±0.5% decline in quadriceps CSA in the intermittent vs continuous feeding group, respectively (both P0.05). Moreover, feeding pattern did not modulate the bed rest-induced decline in insulin sensitivity (-46±3% vs 39±3%; P0.05). Myofibrillar protein synthesis rates during bed rest did not differ between the intermittent and continuous feeding group (1.33±0.07 vs 1.50±0.13%·d−1, respectively; P>0.05). In conclusion, dietary feeding pattern does not modulate the loss of muscle mass or the decline in metabolic health during one week of bed rest in healthy men

Adaptation of rat fast-twitch muscle to endurance activity is underpinned by changes to protein degradation as well as protein synthesis.

Muscle adaptations to exercise are underpinned by alterations to the abundance of individual proteins, which may occur through a change either to the synthesis or degradation of each protein. We used deuterium oxide (2 H2 O) labeling and chronic low-frequency stimulation (CLFS) in vivo to investigate the synthesis, abundance, and degradation of individual proteins during exercise-induced muscle adaptation. Independent groups of rats received CLFS (10 Hz, 24 h/d) and 2 H2 O for 0, 10, 20, or 30 days. The extensor digitorum longus (EDL) was isolated from stimulated (Stim) and contralateral non-stimulated (Ctrl) legs. Proteomic analysis encompassed 38 myofibrillar and 46 soluble proteins and the rates of change in abundance, synthesis, and degradation were reported in absolute (ng/d) units. Overall, synthesis and degradation made equal contributions to the adaptation of the proteome, including instances where a decrease in protein-specific degradation primarily accounted for the increase in abundance of the protein

Short-term muscle disuse induces a rapid and sustained decline in daily myofibrillar protein synthesis rates

This is the author accepted manuscript. The final version is available from the American Physiological Society via the DOI in this recordIntroduction: Short-term muscle disuse has been reported to lower both post-absorptive and post-prandial myofibrillar protein synthesis rates. This study assessed the impact of disuse on daily myofibrillar protein synthesis rates following acute (2 days) and more prolonged (7 days) muscle disuse under free living conditions. Methods: Thirteen healthy young men (age, 20±1 y; BMI, 23±1 kg·m-2) underwent 7 days of unilateral leg immobilization via a knee brace with the non-immobilized leg acting as a control. Four days prior to immobilization participants ingested 400 mL 70% deuterated water, with 50 mL doses consumed daily thereafter. Upper leg bilateral MRI scans and muscle biopsies were collected before, and after 2 and 7 days of immobilization to determine quadriceps volume and daily myofibrillar protein synthesis rates. Results: Immobilization reduced quadriceps volume in the immobilized leg by 1.7±0.3 and 6.7±0.6 % after 2 and 7 days, respectively, with no changes in the control leg. Over the one week immobilization period myofibrillar protein synthesis rates were 36±4% lower in the immobilized (0.81±0.04%·d-1) compared with the control (1.26±0.04%·d-1) leg (P<0.001). Myofibrillar protein synthesis rates in the control leg did not change over time (P=0.775), but in the immobilized leg were numerically lower during the 0-2 day period (16±6%, 1.11±0.09%·d-1, P=0.153) and were significantly lower during the 2-7 day period (44±5%, 0.70±0.06%·d-1, P<0.001) when compared with the control leg. Conclusion: One week of muscle disuse induces a rapid and sustained decline in daily myofibrillar protein synthesis rates in healthy young men.University of MaastrichtRoyal SocietyUniversity of ExeterNational Institute for Health Research (NIHR

Galaxy And Mass Assembly (GAMA): the wavelength dependence of galaxy structure versus redshift and luminosity

We study how the sizes and radial profiles of galaxies vary with wavelength, by fitting Sersic functions simultaneously to imaging in nine optical and near-infrared bands. To quantify the wavelength dependence of effective radius we use the ratio, $\mathcal{R}$, of measurements in two restframe bands. The dependence of Sersic index on wavelength, $\mathcal{N}$, is computed correspondingly. Vulcani et al. (2014) have demonstrated that different galaxy populations present sharply contrasting behaviour in terms of $\mathcal{R}$ and $\mathcal{N}$. Here we study the luminosity dependence of this result. We find that at higher luminosities, early-type galaxies display a more substantial decrease in effective radius with wavelength, whereas late-types present a more pronounced increase in Sersic index. The structural contrast between types thus increases with luminosity. By considering samples at different redshifts, we demonstrate that lower data quality reduces the apparent difference between the main galaxy populations. However, our conclusions remain robust to this effect. We show that accounting for different redshift and luminosity selections partly reconciles the size variation measured by Vulcani et al. with the weaker trends found by other recent studies. Dividing galaxies by visual morphology confirms the behaviour inferred using morphological proxies, although the sample size is greatly reduced. Finally, we demonstrate that varying dust opacity and disc inclination can account for features of the joint distribution of $\mathcal{R}$ and $\mathcal{N}$ for late-type galaxies. However, dust does not appear to explain the highest values of $\mathcal{R}$ and $\mathcal{N}$. The bulge-disc nature of galaxies must also contribute to the wavelength-dependence of their structure

Galaxy and Mass Assembly (GAMA): Accurate number densities and environments of massive ultracompact galaxies at 0.02 < z < 0.3

Massive Ultracompact Galaxies (MUGs) are common at z=2-3, but very rare in the nearby Universe. Simulations predict that the few surviving MUGs should reside in galaxy clusters, whose large relative velocities prevent them from merging, thus maintaining their original properties (namely stellar populations, masses, sizes and dynamical state). We take advantage of the high-completeness, large-area spectroscopic GAMA survey, complementing it with deeper imaging from the KiDS and VIKING surveys. We find a set of 22 bona-fide MUGs, defined as having high stellar mass (>8x10^10 M_Sun) and compact size (R_e ~ 10^10 M_Sun Kpc^-2). Interestingly, a large fraction feature close companions -- at least in projection -- suggesting that many (but not all) live in the central regions of groups. Halo masses show these galaxies inhabit average-mass groups. As MUGs are found to be almost equally distributed among environments of different masses, their relative fraction is higher in more massive overdensities, matching the expectations that some of these galaxies fell in these regions at early times. However, there must be another channel leading some of these galaxies to an abnormally low merger history because our sample shows a number of objects that do not inhabit particularly dense environments. (abridged

Galaxy And Mass Assembly (GAMA): growing up in a bad neighbourhood - how do low-mass galaxies become passive?

Both theoretical predictions and observations of the very nearby Universe suggest that low-mass galaxies (log$_{10}$[M$_{*}$/M$_{\odot}$]<9.5) are likely to remain star-forming unless they are affected by their local environment. To test this premise, we compare and contrast the local environment of both passive and star-forming galaxies as a function of stellar mass, using the Galaxy and Mass Assembly survey. We find that passive fractions are higher in both interacting pair and group galaxies than the field at all stellar masses, and that this effect is most apparent in the lowest mass galaxies. We also find that essentially all passive log$_{10}$[M$_{*}$/M$_{\odot}$]<8.5 galaxies are found in pair/group environments, suggesting that local interactions with a more massive neighbour cause them to cease forming new stars. We find that the effects of immediate environment (local galaxy-galaxy interactions) in forming passive systems increases with decreasing stellar mass, and highlight that this is potentially due to increasing interaction timescales giving sufficient time for the galaxy to become passive via starvation. We then present a simplistic model to test this premise, and show that given our speculative assumptions, it is consistent with our observed results