A branching model for intergenerational telomere length dynamics

We build and study an individual based model of the telomere length's evolution in a population across multiple generations. This model is a continuous time typed branching process, where the type of an individual includes its gamete mean telomere length and its age. We study its Malthusian's behaviour and provide numerical simulations to understand the influence of biologically relevant parameters

Preparation and characterizations of glasses in the TeO2–Ga2O3–M2O (M═Li, Na, K) systems

International audienceGlasses in the TeO2–Ga2O3–M2O (M═Li, Na, or K) systems were synthesized by a melt‐quenching technique. The glass forming areas were delimited for each system. Systematic analyses were performed on two series of samples—the first one with a constant TeO2/Ga2O3 ratio of 85/15, that is, [(TeO2)0.85(Ga2O3)0.15]100−x[M2O]x with 0 ≤ x ≤ 25 (with a step of 5 mol%), the second one with a constant alkaline oxide concentration of 10 mol%, that is, [TeO2]90‐y[Ga2O3]y[M2O]10 with 5 ≤ y ≤ 15 (with step of 2.5 mol%). The values of the glass transition temperature, density, and optical transmission parameters (the positions of short‐ and long‐wavelength absorption edge and the maximum transmittance value) were determined. The changes in these parameters were studied for varying glass compositions. In addition, the values of refractive index were measured at various wavelengths across the whole transparency region reaching from the visible up to the mid‐infrared range

Chicoric acid is an antioxidant molecule that stimulates AMP kinase pathway in L6 myotubes and extends lifespan in Caenorhabditis elegans.

Chicoric acid (CA) is a caffeoyl derivative previously described as having potential anti-diabetic properties. As similarities in cellular mechanism similarities between diabetes and aging have been shown, we explored on L6 myotubes the effect of CA on the modulation of intracellular pathways involved in diabetes and aging. We also determined its influence on lifespan of Caenorhabditis elegans worm (C. elegans). In L6 myotubes, CA was a potent reactive oxygen species (ROS) scavenger, reducing ROS accumulation under basal as well as oxidative stress conditions. CA also stimulated the AMP-activated kinase (AMPK) pathway and displayed various features associated with AMPK activation: CA (a) enhanced oxidative enzymatic defences through increase in glutathion peroxidase (GPx) and superoxide dismutase (SOD) activities, (b) favoured mitochondria protection against oxidative damage through up-regulation of MnSOD protein expression, (c) increased mitochondrial biogenesis as suggested by increases in complex II and citrate synthase activities, along with up-regulation of PGC-1α mRNA expression and (d) inhibited the insulin/Akt/mTOR pathway. As AMPK stimulators (e.g. the anti-diabetic agent meformin or polyphenols such as epigallocatechingallate or quercetin) were shown to extend lifespan in C. elegans, we also determined the effect of CA on the same model. A concentration-dependant lifespan extension was observed with CA (5-100 μM). These data indicate that CA is a potent antioxidant compound activating the AMPK pathway in L6 myotubes. Similarly to other AMPK stimulators, CA is able to extend C. elegans lifespan, an effect measurable even at the micromolar range. Future studies will explore CA molecular targets and give new insights about its possible effects on metabolic and aging-related diseases

Influence of chicoric acid on antioxidant enzymes in L6 myotubes.

<p>Cells were cultured in the presence or absence of CA (50 µM) for 10 days before measurements of the enzymatic activities of GPx (<b>A</b>) or SOD (<b>B</b>), or analysis of MnSOD protein expression (<b>C</b>). Enzymatic activities are expressed as mU/mg protein and indicated as means ± SEM (n = 5); significantly different from control at * p<0.05. Representative immunoblot is shown.</p

Influence of chicoric acid on PGC-1α mRNA expression in L6 myotubes.

<p>Cells were treated with 5 µM or 50 µM CA for the indicated times. PGC-1α mRNA levels were measured by quantitative RT PCR and normalized relatively to RPS9 mRNA expression. Values are means ± SEM (n = 5); significantly different from control of the same time at * p<0.05.</p

Influence of chicoric acid on AMPK/ACC pathway in L6 myotubes.

<p>Cells were treated with the indicated concentrations of CA for 1(Thr172) and tubulin expression (<b>A</b>); influence of compound C on AMPK phosphorylation (<b>B</b>); phosphorylated ACC (Ser79) and tubulin expression (<b>C</b>). Data are expressed relatively to control value (without CA). Values are means ± SEM (n = 5). Significantly different from control at * p<0.05, ** p<0.01. Representative immunoblots are shown.</p

Influence of chicoric acid on Akt and mTOR phosphorylations in L6 myotubes.

<p>Cells were treated with 5 or 50 µM CA for 1 hour with or without 100 nM insulin and proteins were extracted for western blot analyses of phosphorylated Akt (Ser473) or tubulin (<b>A</b>), phosphorylated mTOR (Ser 2448) or tubulin (<b>B</b>). Data are expressed relatively to the value obtained with insulin (without CA) (<b>A</b>) or relatively to the value obtained without insulin (without CA) (<b>B</b>). Values are means ± SEM (n = 5). * p<0.05, ** p<0.01. Representative immunoblots are shown.</p

Chicoric acid-dependent lifespan modulation of <i>C. elegans</i>.

<p>The tabulated data show the average results plotted in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0078788#pone-0078788-g008" target="_blank">Figure 8</a>. Up to two independent trials were done at 20°C with identical results. Worms were fed with the E. coli HT115 strain bacteria (see Material and Methods section). XLSTAT-life statistical software (Addinsoft, New York, NY, USA) was used to plot survival data by the Kaplan Meier method and differences between survival curves calculated using the Log-Rank test with 95% confidence. (a) Represents the 50th percentile (the age when the survival fraction of animals reaches 0.50). (b) Experiment identification code. (c) Probability of being identical to other lifespan experiments given in parentheses. (d) Total death scored (number of censored values).</p

Influence of chicoric acid on mitochondrial activity in L6 myotubes.

<p>Cells were cultured in the presence or absence of 50 µM CA for 10 days before measurement of mitochondrial activities. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0078788#pone-0078788-g004" target="_blank">Figure 4</a> illustrates complex II maximal activity (CII; <b>A</b>); complexes II+III maximal activity (CII+III; <b>B</b>); complex IV maximal activity (CIV; <b>C</b>); and citrate synthase maximal activity (CS; <b>D</b>). Enzymatic activities are expressed as mU/mg protein and indicated as means ± SEM (n = 5); significantly different from control at * p<0.05.</p