Age related changes in speed and mechanism of adult skeletal muscle stem cell migration

Skeletal muscle undergoes a progressive age-related loss in mass and function. Preservation of muscle mass depends in part on satellite cells, the resident stem cells of skeletal muscle. Reduced satellite cell function may contribute to the age-associated decrease in muscle mass. Here we focused on characterising the effect of age on satellite cell migration. We report that aged satellite cells migrate at less than half the speed of young cells. In addition, aged cells show abnormal membrane extension and retraction characteristics required for amoeboid based cell migration. Aged satellite cells displayed low levels of integrin expression. By deploying a mathematical model approach to investigate mechanism of migration, we have found that young satellite cells move in a random ‘memoryless’ manner whereas old cells demonstrate superdiffusive tendencies. Most importantly, we show that nitric oxide, a key regulator of cell migration, reversed the loss in migration speed and reinstated the unbiased mechanism of movement in aged satellite cells. Finally we found that although Hepatocyte Growth Factor increased the rate of aged satellite cell movement it did not restore the memoryless migration characteristics displayed in young cells. Our study shows that satellite cell migration, a key component of skeletal muscle regeneration, is compromised during aging. However, we propose clinically approved drugs could be used to overcome these detrimental changes.

Investigating age related changes in taste and affects on sensory perceptions of oral nutritional supplements

Background: sip feeds are oral nutritional supplements (ONSs) that are commonly prescribed to malnourished patients to improve their nutritional and clinical status. However, ONSs are poorly consumed and frequently wasted, with sweetness being identified as one of the factors leading to patients’ dislike of ONSs. Objectives: to investigate if age affects sweetness thresholds and if this impacts upon perceived sweetness intensity, hedonic (sweetness and overall) and ranked preference of ONS products. Design: prospective, observational. Subjects: thirty-six young adults (18–33 years) and 48 healthy older adults (63–85 years). Setting: Department of Food and Nutritional Sciences and the Clinical Health Sciences at the University of Reading. Methods: detection and recognition threshold levels, basic taste identification and ‘just about right’ level of sweetness were examined. Three ONSs (chocolate, vanilla, strawberry) and sucrose solutions were evaluated for hedonic sweetness, overall hedonic liking, sweetness intensity and rank preference. Results: significant differences were found in both sweetness detection and recognition thresholds (P = 0.0001) between young and older adults, with older adults more likely to incorrectly identify the taste (P = 0.0001). Despite the deterioration in sweetness sensitivity among the older adults, there were no significant differences found in sweetness intensity perceived for the ONS products presented (P > 0.05) when compared with the young adults. However, across both groups sweetness intensity was found to be correlated with overall product dislike across all flavour variants tested (R = 0.398, P = 0.0001). Conclusions: sweetness appears to be one of many factors contributing to the dislike of ONSs. Manufacturers are encouraged to reconsider the formulations of these products so that beneficial effects of ONSs can be delivered in a more palatable and acceptable form and wastage reduced.

Proteomic analysis of redox- and ErbB2-dependent changes in mammary luminal epithelial cells using cysteine- and lysine-labelling two-dimensional difference gel electrophoresis

Differential protein expression analysis based on modification of selected amino acids with labelling reagents has become the major method of choice for quantitative proteomics. One such methodology, two-dimensional difference gel electrophoresis (2-D DIGE), uses a matched set of fluorescent N-hydroxysuccinimidyl (NHS) ester cyanine dyes to label lysine residues in different samples which can be run simultaneously on the same gels. Here we report the use of iodoacetylated cyanine (ICy) dyes (for labelling of cysteine thiols, for 2-D DIGE-based redox proteomics. Characterisation of ICy dye labelling in relation to its stoichiometry, sensitivity and specificity is described, as well as comparison of ICy dye with NHS-Cy dye labelling and several protein staining methods. We have optimised conditions for labelling of nonreduced, denatured samples and report increased sensitivity for a subset of thiol-containing proteins, allowing accurate monitoring of redox-dependent thiol modifications and expression changes. Cysteine labelling was then combined with lysine labelling in a multiplex 2-D DIGE proteomic study of redox-dependent and ErbB2-dependent changes in epithelial cells exposed to oxidative stress. This study identifies differentially modified proteins involved in cellular redox regulation, protein folding, proliferative suppression, glycolysis and cytoskeletal organisation, revealing the complexity of the response to oxidative stress and the impact that overexpression of ErbB2 has on this response.

Proteomic analysis of redox- and ErbB2-dependent changes in mammary luminal epithelial cells using cysteine- and lysine-labelling two-dimensional difference gel electrophoresis

Differential protein expression analysis based on modification of selected amino acids with labelling reagents has become the major method of choice for quantitative proteomics. One such methodology, two-dimensional difference gel electrophoresis (2-D DIGE), uses a matched set of fluorescent N-hydroxysuccinimidyl (NHS) ester cyanine dyes to label lysine residues in different samples which can be run simultaneously on the same gels. Here we report the use of iodoacetylated cyanine (ICy) dyes (for labelling of cysteine thiols, for 2-D DIGE-based redox proteomics. Characterisation of ICy dye labelling in relation to its stoichiometry, sensitivity and specificity is described, as well as comparison of ICy dye with NHS-Cy dye labelling and several protein staining methods. We have optimised conditions for labelling of nonreduced, denatured samples and report increased sensitivity for a subset of thiol-containing proteins, allowing accurate monitoring of redox-dependent thiol modifications and expression changes, Cysteine labelling was then combined with lysine labelling in a multiplex 2-D DIGE proteomic study of redox-dependent and ErbB2-dependent changes in epithelial cells exposed to oxidative stress. This study identifies differentially modified proteins involved in cellular redox regulation, protein folding, proliferative suppression, glycolysis and cytoskeletal organisation, revealing the complexity of the response to oxidative stress and the impact that overexpression of ErbB2 has on this response.

Age-related changes in the functional neuroanatomy of overt speech production

Alterations of existing neural networks during healthy aging, resulting in behavioral deficits and changes in brain activity, have been described for cognitive, motor, and sensory functions. To investigate age-related changes in the neural circuitry underlying overt non-lexical speech production, functional MRI was performed in 14 healthy younger (21–32 years) and 14 healthy older individuals (62–84 years). The experimental task involved the acoustically cued overt production of the vowel /a/ and the polysyllabic utterance /pataka/. In younger and older individuals, overt speech production was associated with the activation of a widespread articulo-phonological network, including the primary motor cortex, the supplementary motor area, the cingulate motor areas, and the posterior superior temporal cortex, similar in the /a/ and /pataka/ condition. An analysis of variance with the factors age and condition revealed a significant main effect of age. Irrespective of the experimental condition, significantly greater activation was found in the bilateral posterior superior temporal cortex, the posterior temporal plane, and the transverse temporal gyri in younger compared to older individuals. Significantly greater activation was found in the bilateral middle temporal gyri, medial frontal gyri, middle frontal gyri, and inferior frontal gyri in older vs. younger individuals. The analysis of variance did not reveal a significant main effect of condition and no significant interaction of age and condition. These results suggest a complex reorganization of neural networks dedicated to the production of speech during healthy aging.

Developmental changes in the balance of disparity, blur and looming/proximity cues to drive ocular alignment and focus

Accurate co-ordination of accommodation and convergence is necessary to view near objects and develop fine motor co-ordination. We used a remote haploscopic videorefraction paradigm to measure longitudinal changes in simultaneous ocular accommodation and vergence to targets at different depths, and to all combinations of blur, binocular disparity, and change-in-size (“proximity”) cues. Infants were followed longitudinally and compared to older children and young adults, with the prediction that sensitivity to different cues would change during development. Mean infant responses to the most naturalistic condition were similar to those of adults from 6-7 weeks (accommodation) and 8-9 weeks (vergence). Proximity cues influenced responses most in infants less than 14 weeks of age, but sensitivity declined thereafter. Between 12-28 weeks of age infants were equally responsive to all three cues, while in older children and adults manipulation of disparity resulted in the greatest changes in response. Despite rapid development of visual acuity (thus increasing availability of blur cues), responses to blur were stable throughout development. Our results suggest that during much of infancy, vergence and accommodation responses are not dependent on the development of specific depth cues, but make use of any cues available to drive appropriate changes in response.

Changes in the extent of glaciers in the Eastern Terskey Alatoo, the Central Tien-Shan, in response to climatic fluctuations in between the end of the 19th and the beginning of the 21st century

Changes in the extent of glaciers and rates of glacier termini retreat in the eastern Terskey-Alatoo Range, the Tien Shan Mountains, Central Asia have been evaluated using the remote sensing techniques. Changes in the extent of 335 glaciers between the end of the Little Ice Age (LIA; mid-19th century), 1990 and 2003 have been estimated through the delineation of glacier outlines and the LIA moraine positions on the Landsat TM and ASTER imagery for 1990 and 2003 respectively. By 2003, the glacier surface area had decreased by 19% of the LIA value, which constitutes a 76 km(2) reduction in glacier surface area. Mapping of 109 glaciers using the 1965 1:25,000 maps revealed that glacier surface area decreased by 12.6% of the 1965 value between 1965 and 2003. Detailed mapping of 10 glaciers using historical maps and aerial photographs from the 1943-1977 period, has enabled glacier extent variations over the 20th century to be identified with a higher temporal resolution. Glacial retreat was slow in the early 20th century but increased considerably between 1943 and 1956 and then again after 1977. The post-1990 period has been marked by the most rapid glacier retreat since the end of the LIA. The observed changes in the extent of glaciers are in line with the observed climatic warming. The regional weather stations have revealed a strong climatic warming during the ablation season since the 1950s at a rate of 0.02-0.03 degrees Ca-1. At the higher elevations in the study area represented by the Tien Shan meteorological station, the summer warming was accompanied by negative anomalies in annual precipitation in the 1990s enhancing glacier retreat. However, trends in precipitation in the post-1997 period cannot be evaluated due to the change in observational practices at this station. Neither station in the study area exhibits significant long-term trends in precipitation. Crown Copyright (C) 2009 Published by Elsevier B.V. All rights reserved.

Age-associated changes in protein oxidation and proteasome activities in rat brain: modulation by antioxidants

The free radical theory of ageing postulates that age-associated neurodegeneration is caused by an imbalance between pro-oxidants and antioxidants resulting in oxidative stress. The current study showed regional variation in brain susceptibility to age-associated oxidative stress as shown by increased lipofuscin deposition and protein carbonyl levels in male rats of age 15-16 months compared to control ones (3-5 months). The hippocampus is the area most vulnerable to change compared to the cortex and cerebellum. However, proteasomal enzyme activity was not affected by age in any of the brain regions studied. Treatment with melatonin or coenzyme Q10 for 4 weeks reduced the lipofuscin content of the hippocampus and carbonyl level. However, both melatonin and coenzyme Q10 treatments inhibited beta-glutamyl peptide hydrolase activity. This suggests that these molecules can alter proteasome function independently of their antioxidant actions. (c) 2005 Elsevier Inc. All rights reserved.

The dynamics of threat, fear and intentionality in the conduct disorders: longitudinal findings in the children of women with post-natal depression

This paper considers how environmental threat may contribute to the child's use of avoidant strategies to regulate negative emotions, and how this may interact with high emotional reactivity to create vulnerability to conduct disorder symptoms. We report a study based on the hypothesis that interpreting others' behaviours in terms of their motives and emotions - using the intentional stance - promotes effective social action, but may lead to fear in threatful situations, and that inhibiting the intentional stance may reduce fear but promote conduct disorder symptoms. We assessed 5-year-olds' use of the intentional stance with an intentionality scale, contrasting high and low threat doll play scenarios. In a sample of 47 children of mothers with post-natal depression ( PND) and 35 controls, children rated as securely attached with their mothers at the age of 18 months were better able to preserve the intentional stance than insecure children in high threat scenarios, but not in low threat scenarios. Girls had higher intentionality scores than boys across all scenarios. Only intentionality in the high threat scenario was associated with teacher-rated conduct disorder symptoms, and only in the children of women with PND. Intentionality mediated the associations between attachment security and gender and conduct disorder symptoms in the PND group.

Regime dependent changes in global precipitation

Assessment of changes in precipitation (P) as a function of percentiles of surface temperature (T) and 500 hPa vertical velocity (ω) are presented, considering present-day simulations and observational estimates from the Global Precipitation Climatology Project (GPCP) combined with the European Centre for Medium-range Weather Forecasts Interim reanalysis (ERA Interim). There is a tendency for models to overestimate P in the warm, subsiding regimes compared to GPCP, in some cases by more than 100%, while many models underestimate P in the moderate temperature regimes. Considering climate change projections between 1980–1999 and 2080–2099, responses in P are characterised by dP/dT ≥ 4%/K over the coldest 10–20% of land points and over warm, ascending ocean points while P declines over the warmest, descending regimes (dP/dT ∼ − 4%/K for model ensemble means). The reduced Walker circulation limits this contrasting dP/dT response in the tropical wet and dry regimes only marginally. Around 70% of the global surface area exhibits a consistent sign for dP/dT in at least 6 out of a 7-member model ensemble when considering P composites in terms of dynamic regime.

Elevation-dependent warming in mountain regions of the world

There is growing evidence that the rate of warming is amplified with elevation, such that high-mountain environments experience more rapid changes in temperature than environments at lower elevations. Elevation-dependent warming (EDW) can accelerate the rate of change in mountain ecosystems, cryospheric systems, hydrological regimes and biodiversity. Here we review important mechanisms that contribute towards EDW: snow albedo and surface-based feedbacks; water vapour changes and latent heat release; surface water vapour and radiative flux changes; surface heat loss and temperature change; and aerosols. All lead to enhanced warming with elevation (or at a critical elevation), and it is believed that combinations of these mechanisms may account for contrasting regional patterns of EDW. We discuss future needs to increase knowledge of mountain temperature trends and their controlling mechanisms through improved observations, satellite-based remote sensing and model simulations.

Changes in physical properties of bovine milk from the colostrum period to early lactation

The aim of this study was to analyze individual cows' samples from the colostrum, postcolostrum, and early lactation periods to investigate how milk composition, physical properties, stability, and suitability for processing change throughout this period. Attention was paid to the first week postpartum in which the composition of bovine mammary secretion can change markedly. Properties including pH, titratable acidity, ethanol stability (ES), rennet clotting time, and casein micelle size were analyzed, together with some compositional factors such as fat, total protein, lactose, total and ionic calcium, magnesium, citrate, phosphorus, sodium, and potassium. Total Ca (36.2 mM) and free ionic Ca (2.58 mM), Mg (5.9 mM), P (32.2 mM), and Na (24.1 mM) appeared to be high on d 5 postpartum, having decreased substantially over the first 5 d; they gradually decreased thereafter. The average pH on d 5 was only 6.49, compared with 6.64 at 1 mo postpartum. Stability measurements showed that the average ES on d 5 was 70% and the rennet clotting time was 12.2 min, which were significantly lower than values at later stages. A number of milk properties including ES, pH, protein content, and Ca2+ concentration could be useful for identifying the point of transition from colostrum to the early lactation period. Knowing the composition and physical properties of colostrum and postcolostrum secretions will help establish when such milk is suitable for processing and determine the best use for that milk.