Mathematical Modelling of Metabolic Regulation in Aging

The underlying cellular mechanisms that characterize aging are complex and multifaceted. However, it is emerging that aging could be regulated by two distinct metabolic hubs. These hubs are the pathway defined by the mammalian target of rapamycin (mTOR) and that defined by the NAD+-dependent deacetylase enzyme, SIRT1. Recent experimental evidence suggests that there is crosstalk between these two important pathways; however, the mechanisms underpinning their interaction(s) remains poorly understood. In this review, we propose using computational modelling in tandem with experimentation to delineate the mechanism(s). We briefly discuss the main modelling frameworks that could be used to disentangle this relationship and present a reduced reaction pathway that could be modelled. We conclude by outlining the limitations of computational modelling and by discussing opportunities for future progress in this area

Effect of Ischemic Preconditioning (IPC) on Recovery of Exercise Performance Following a Bout of Exercise to Volitional Exhaustion

The purpose of the present study was to investigate the effect of ischemic preconditioning (IPC) on the recovery of exercise performance following maximal, incremental exercise. A total of 13 healthy males volunteered to participate, undertaking three experimental trials involving a constant work-rate bout of severe intensity exercise undertaken to the limit of tolerance that was preceded by a 40-min recovery period consequent to a maximal, incremental exercise test. During the recovery period, participants underwent IPC at 220 mmHg, sham IPC (SHAM; 20 mmHg), and passive rest (CON). Exercise tolerance time was higher following IPC as compared to SHAM and CON {199 ± 36 (CON) vs. 203 ± 35 (SHAM) vs. 219 ± 34 (IPC), p = 0.03}. This effect was accompanied by a tendency toward an augmented increase in blood lactate from rest to exercise in IPC compared to SHAM and CON (p = 0.08). There was no effect of IPC on oxygen uptake kinetics or muscle oxygenation as indicated via near-infrared spectroscopy. IPC may therefore have the capacity to augment recovery from prior maximal exercise, but this does not appear to be due to enhancements to oxygen uptake kinetics or muscle oxygenatio

Evaluating the progressive cardiovascular health benefits of short term high intensity interval training

Purpose High-intensity training is recognised as a time-efficient way of improving aerobic fitness. However, there is a lack of consensus regarding the temporal nature of adaptation response and which peripheral and cardiac changes occur using the same exercise stimulus and protocol. Therefore, this study aimed to evaluate the progression of vascular and cardiac changes over a 6-week training period. Methods Twelve healthy males (age 21 ± 2 years; 42.5 ± 8.3 ml min−1 kg−1) participated in a high-intensity training programme consisting of 1-min sprints, interspersed with 2 min active recovery, 3 days/week for 6 weeks on a cycle ergometer. Cardiac, vascular, blood lipids and VO2max measurements were taken at 0, 3 and 6 weeks and compared against a participant matched control group (age 21 ± 2 years; 37.7 ± 8.3 ml min−1 kg−1). Results There was a significant improvement in VO2max (42.5 ± 8.3–47.4 ± 8.5 ml min−1 kg−1; p = 0.009) in the training group and a significant decrease in systolic blood pressure (8%) from 0 to 6 weeks (p = 0.025). There was a small yet significant decrease in ejection fraction and increased end-systolic volume in both groups over time (p = 0.01) with no significant interaction effect (p > 0.05). A between-group difference in peak velocity of early diastolic mitral annular motion was also observed (p = 0.01). No improvements were seen in blood lipid profiles, central arterial stiffness and cardiometabolic risk score. Conclusions Six weeks of high-intensity training increases aerobic fitness and is enough to stimulate initial reductions in peripheral pressure, but not sufficient to elicit structural and functional cardiac changes, reduce arterial stiffness or lower CV risk

Intra-unit reliability and movement variability of submission grappling external load as measured by torso mounted accelerometery

Submission grappling consists of skills and movements used in combat sports to physically control opponents whilst trying to apply choke holds and joint locks. There is currently no accepted method of monitoring external load in grappling-based sports due to the absence of key variables such as distance, velocity or time. The primary aim of this study was to determine whether PlayerLoad is a reliable variable for measuring external load of submission grappling movements, with a secondary aim of determining the between repetition variance of submission grappling movements. 7 experienced submission grapplers were recruited. Each wore a torso mounted Catapult® Optimeye S5 microelectromechanical systems (MEMS) device and completed 5 repetitions of each of the following: 4 submission techniques; 6 transition techniques; 2 guard pass techniques; 2 takedown techniques. Accumulated PlayerLoad (PLdACC) was recorded as a marker of absolute load, with accumulated PlayerLoad per minute (PLdACC∙min-1) representing relative load. Reliability of each was assessed using intraclass correlation coefficient (ICC(3,1)) (≥ .70). Between repetition movement variation was assessed via coefficient of variation with 95% confidence intervals (CV, 95%CI) (acceptable ≤ 15%, good ≤ 10%). PLdACC ICC(3,1) range = .78–.98, with CV range = 9–22%. PLdACC∙min-1 ICC(3,1) range = .83–98, with CV range = 11–19%. Though several variables displayed CV > 15%, all had 95%CI lower boundaries ≤ 15%. Whilst PlayerLoad was found to be a reliable measure for submission grappling, relatively high CVs across most techniques examined suggest PlayerLoad may not be appropriate for measuring changes in external load for individual movements in submission grappling. However, it may prove a useful tool for monitoring the external load of full, grappling-based, training sessions within an individual

Glassy timescale divergence and anomalous coarsening in a kinetically constrained spin chain

We analyse the out of equilibrium behavior of an Ising spin chain with an asymmetric kinetic constraint after a quench to a low temperature T. In the limit T\to 0, we provide an exact solution of the resulting coarsening process. The equilibration time exhibits a `glassy' divergence \teq=\exp(const/T^2) (popular as an alternative to the Vogel-Fulcher law), while the average domain length grows with a temperature dependent exponent, \dbar ~ t^{T\ln 2}. We show that the equilibration time \teq also sets the timescale for the linear response of the system at low temperatures.Comment: 4 pages, revtex, includes two eps figures. Proof of energy barrier hierarchy added. Version to be published in Phys Rev Let

Free energy and configurational entropy of liquid silica: fragile-to-strong crossover and polyamorphism

Recent molecular dynamics (MD) simulations of liquid silica, using the ``BKS'' model [Van Beest, Kramer and van Santen, Phys. Rev. Lett. {\bf 64}, 1955 (1990)], have demonstrated that the liquid undergoes a dynamical crossover from super-Arrhenius, or ``fragile'' behavior, to Arrhenius, or ``strong'' behavior, as temperature $T$ is decreased. From extensive MD simulations, we show that this fragile-to-strong crossover (FSC) can be connected to changes in the properties of the potential energy landscape, or surface (PES), of the liquid. To achieve this, we use thermodynamic integration to evaluate the absolute free energy of the liquid over a wide range of density and $T$. We use this free energy data, along with the concept of ``inherent structures'' of the PES, to evaluate the absolute configurational entropy $S_c$ of the liquid. We find that the temperature dependence of the diffusion coefficient and of $S_c$ are consistent with the prediction of Adam and Gibbs, including in the region where we observe the FSC to occur. We find that the FSC is related to a change in the properties of the PES explored by the liquid, specifically an inflection in the $T$ dependence of the average inherent structure energy. In addition, we find that the high $T$ behavior of $S_c$ suggests that the liquid entropy might approach zero at finite $T$, behavior associated with the so-called Kauzmann paradox. However, we find that the change in the PES that underlies the FSC is associated with a change in the $T$ dependence of $S_c$ that elucidates how the Kauzmann paradox is avoided in this system. Finally, we also explore the relation of the observed PES changes to the recently discussed possibility that BKS silica exhibits a liquid-liquid phase transition, a behavior that has been proposed to underlie the observed polyamorphism of amorphous solid silica.Comment: 14 pages, 18 figure

Frequency dependent specific heat of viscous silica

We apply the Mori-Zwanzig projection operator formalism to obtain an expression for the frequency dependent specific heat c(z) of a liquid. By using an exact transformation formula due to Lebowitz et al., we derive a relation between c(z) and K(t), the autocorrelation function of temperature fluctuations in the microcanonical ensemble. This connection thus allows to determine c(z) from computer simulations in equilibrium, i.e. without an external perturbation. By considering the generalization of K(t) to finite wave-vectors, we derive an expression to determine the thermal conductivity \lambda from such simulations. We present the results of extensive computer simulations in which we use the derived relations to determine c(z) over eight decades in frequency, as well as \lambda. The system investigated is a simple but realistic model for amorphous silica. We find that at high frequencies the real part of c(z) has the value of an ideal gas. c'(\omega) increases quickly at those frequencies which correspond to the vibrational excitations of the system. At low temperatures c'(\omega) shows a second step. The frequency at which this step is observed is comparable to the one at which the \alpha-relaxation peak is observed in the intermediate scattering function. Also the temperature dependence of the location of this second step is the same as the one of the $\alpha-$peak, thus showing that these quantities are intimately connected to each other. From c'(\omega) we estimate the temperature dependence of the vibrational and configurational part of the specific heat. We find that the static value of c(z) as well as \lambda are in good agreement with experimental data.Comment: 27 pages of Latex, 8 figure

Ionic liquids containing tricyanomethanide anions: physicochemical characterisation and performance as electrochemical double-layer capacitor electrolytes

We investigated the use of fluorine free ionic liquids (ILs) containing the tricyanomethanide anion ([C(CN)3]) as an electrolyte in electrochemical double-layer capacitors (EDLCs). Three cations were used; 1-butyl-3-methylimidazolium ([Im1,4]), N-butyl-N-methylpyrrolidinium ([Pyr1,4]) and N-butyl-N-methylpiperidinium ([Pip1,4]). Their physicochemical properties are discussed alongside with their performance as electrolytes. We found that the cyano-based ILs present higher ionic conductivity (9.4, 8.7 and 4.2 mS cm−1 at 25 °C for [Im1,4], [Pyr1,4] and [Pip1,4], respectively) than the widely studied IL containing the bis(trifluoromethylsulfonyl)imide anion, namely [Pyr1,4][Tf2N] (2.7 mS cm−1 at 25 °C). Of the three ILs investigated, [Pip1,4][C(CN)3] presents the widest electrochemical stability window, 3.0 V, while [Pyr1,4][C(CN)3] is stable up to 2.9 V and its [Tf2N] analogue can operate at 3.5 V. Despite operating at a lower voltage, [Pyr1,4][C(CN)3] EDLC is capable of delivering up to 4.5 W h kg−1 when operating at high specific power of 7.2 kW kg−1, while its [Pyr1,4][Tf2N] counterpart only delivered 3.0 W h kg−1 when operated at similar power

Effects of exercise and whey protein on muscle mass, fat mass, myoelectrical muscle fatigue and health-related quality of life in older adults: a secondary analysis of the Liverpool Hope University-Sarcopenia Ageting Trial (LHU-SAT)

Purpose To investigate the efects of exercise in combination with, or without, a leucine-enriched whey protein supplement on muscle mass, fat mass, myoelectrical muscle fatigue and health-related quality of life (HR-QOL) in older adults. Methods 100 community-dwelling older adults [52% women, age: 69±6years (mean±SD)] were randomised to four [Control (C); Exercise (E); Exercise + Protein (EP); Protein (P)] independent groups. E and EP groups completed 16 weeks of exercise [resistance (2 times/week) and functional (1 time/week]. EP and P groups were also administered a leucine-enriched whey protein supplement (3 times/day) based on body weight (1.5 g/kg/day). Muscle and fat mass (bioelectrical impedance analysis), myoelectrical muscle fatigue (surface electromyography) and HR-QOL (WHOQOL-BREF) were measured pre- and post-intervention. Results At post-intervention, the rectus femoris (E:−4.8%/min, p=0.007, ES=0.86; EP:−3.3%/min, p=0.045,ES=0.58) and bicep femoris (E: − 3.9%/min, p 0.05). Conclusion Physical exercise is a potent method to improve myoelectrical muscle fatigue and HR-QOL in older adults. However, leucine-enriched whey protein did not augment this response in those already consuming suicient quantities of protein at trial enrolment