Restoration of energy homeostasis by SIRT6 extends healthy lifespan

Aging leads to a gradual decline in physical activity and disrupted energy homeostasis. The NAD+-dependent SIRT6 deacylase regulates aging and metabolism through mechanisms that largely remain unknown. Here, we show that SIRT6 overexpression leads to a reduction in frailty and lifespan extension in both male and female B6 mice. A combination of physiological assays, in vivo multi-omics analyses and 13C lactate tracing identified an age-dependent decline in glucose homeostasis and hepatic glucose output in wild type mice. In contrast, aged SIRT6-transgenic mice preserve hepatic glucose output and glucose homeostasis through an improvement in the utilization of two major gluconeogenic precursors, lactate and glycerol. To mediate these changes, mechanistically, SIRT6 increases hepatic gluconeogenic gene expression, de novo NAD+ synthesis, and systemically enhances glycerol release from adipose tissue. These findings show that SIRT6 optimizes energy homeostasis in old age to delay frailty and preserve healthy aging

Crosstalk between Mitochondrial and Sarcoplasmic Reticulum Ca2+ Cycling Modulates Cardiac Pacemaker Cell Automaticity

Mitochondria dynamically buffer cytosolic Ca(2+) in cardiac ventricular cells and this affects the Ca(2+) load of the sarcoplasmic reticulum (SR). In sinoatrial-node cells (SANC) the SR generates periodic local, subsarcolemmal Ca(2+) releases (LCRs) that depend upon the SR load and are involved in SANC automaticity: LCRs activate an inward Na(+)-Ca(2+) exchange current to accelerate the diastolic depolarization, prompting the ensemble of surface membrane ion channels to generate the next action potential (AP).To determine if mitochondrial Ca(2+) (Ca(2+) (m)), cytosolic Ca(2+) (Ca(2+) (c))-SR-Ca(2+) crosstalk occurs in single rabbit SANC, and how this may relate to SANC normal automaticity.Inhibition of mitochondrial Ca(2+) influx into (Ru360) or Ca(2+) efflux from (CGP-37157) decreased [Ca(2+)](m) to 80 ± 8% control or increased [Ca(2+)](m) to 119 ± 7% control, respectively. Concurrent with inhibition of mitochondrial Ca(2+) influx or efflux, the SR Ca(2+) load, and LCR size, duration, amplitude and period (imaged via confocal linescan) significantly increased or decreased, respectively. Changes in total ensemble LCR Ca(2+) signal were highly correlated with the change in the SR Ca(2+) load (r(2) = 0.97). Changes in the spontaneous AP cycle length (Ru360, 111 ± 1% control; CGP-37157, 89 ± 2% control) in response to changes in [Ca(2+)](m) were predicted by concurrent changes in LCR period (r(2) = 0.84).A change in SANC Ca(2+) (m) flux translates into a change in the AP firing rate by effecting changes in Ca(2+) (c) and SR Ca(2+) loading, which affects the characteristics of spontaneous SR Ca(2+) release

Study of adsorption states in ZnO—Ag gas-sensitive ceramics using the ECTV curves method

The ZnO—Ag ceramic system as the material for semiconductor sensors of ethanol vapors was proposed quite a long time ago. The main goal of this work was to study surface electron states of this system and their relation with the electric properties of the material. The quantity of doping with Ag2O was changed in the range of 0,1–2,0% of mass. The increase of the Ag doping leads to a shift of the Fermi level down (closer to the valence zone). The paper presents research results on electrical properties of ZnO-Ag ceramics using the method of thermal vacuum curves of electrical conductivity. Changes in the electrical properties during heating in vacuum in the temperature range of 300—800 K were obtained and discussed. The increase of Tvac leads to removal of oxygen from the surface of samples The oxygen is adsorbed in the form of O2– and O– ions and is the acceptor for ZnO. This results in the lowering of the inter-crystallite potential barriers in the ceramic. The surface electron states (SES) above the Fermi level are virtually uncharged. The increase of the conductivity causes desorption of oxygen from the SES settled below the Fermi level of the semiconductor. The model allows evaluating the depth of the Fermi level in the inhomogeneous semiconductor materials

Percolation effects in the capacitive properties of metal-oxide varistors in the range of high voltage

C–V characteristics of ZnO-based ceramic structures used in manufacturing high-voltage and low-voltage varistors of different chemical compositions and manufacturing techniques have been investigated. A correlation between the intensity of electric field corresponding to transition of the C–V characteristics to the negative capacitances and average sizes of grains of a varistor structure has been established. Obtained data have been interpreted with the use of notions of the percolation theory of electric conductivity. The Shklovskii–De Gennes model has been used. It has been shown that on the highly nonlinear segment of C–V characteristics of a varistor structure, the size of an infinite cluster are limited to several intercrystallite potential barriers. This result is observed in all kinds of investigated varistor ceramics

Electrical conductivity of the «polyethylene — vanadium dioxide» composite

Samples of the «polyethylene — VO2» composite have been obtained using technologies for manufacturing self-healing polyswitch fuses. The volume fraction of vanadium dioxide in the samples ranged from 0,25 to 0,6. It is shown that the electrical conductivity of the composite is of percolation character. The paper presents research results of the microstructure, the resistance temperature dependence and current-voltage characteristics of polymer composite samples, as well as the impact of the VO2 content on the samples