Voluntary exercise can strengthen the circadian system in aged mice

Consistent daily rhythms are important to healthy aging according to studies linking disrupted circadian rhythms with negative health impacts. We studied the effects of age and exercise on baseline circadian rhythms and on the circadian system's ability to respond to the perturbation induced by an 8 h advance of the light:dark (LD) cycle as a test of the system's robustness. Mice (male, mPer2luc/C57BL/6) were studied at one of two ages: 3.5 months (n = 39) and >18 months (n = 72). We examined activity records of these mice under entrained and shifted conditions as well as mPER2::LUC measures ex vivo to assess circadian function in the suprachiasmatic nuclei (SCN) and important target organs. Age was associated with reduced running wheel use, fragmentation of activity, and slowed resetting in both behavioral and molecular measures. Furthermore, we observed that for aged mice, the presence of a running wheel altered the amplitude of the spontaneous firing rate rhythm in the SCN in vitro. Following a shift of the LD cycle, both young and aged mice showed a change in rhythmicity properties of the mPER2::LUC oscillation of the SCN in vitro, and aged mice exhibited longer lasting internal desynchrony. Access to a running wheel alleviated some age-related changes in the circadian system. In an additional experiment, we replicated the effect of the running wheel, comparing behavioral and in vitro results from aged mice housed with or without a running wheel (>21 months, n = 8 per group, all examined 4 days after the shift). The impact of voluntary exercise on circadian rhythm properties in an aged animal is a novel finding and has implications for the health of older people living with environmentally induced circadian disruption

Omega-3 Fatty Acids from Fish Oil Lower Anxiety, Improve Cognitive Functions and Reduce Spontaneous Locomotor Activity in a Non-Human Primate

Omega-3 (ω3) polyunsaturated fatty acids (PUFA) are major components of brain cells membranes. ω3 PUFA-deficient rodents exhibit severe cognitive impairments (learning, memory) that have been linked to alteration of brain glucose utilization or to changes in neurotransmission processes. ω3 PUFA supplementation has been shown to lower anxiety and to improve several cognitive parameters in rodents, while very few data are available in primates. In humans, little is known about the association between anxiety and ω3 fatty acids supplementation and data are divergent about their impact on cognitive functions. Therefore, the development of nutritional studies in non-human primates is needed to disclose whether a long-term supplementation with long-chain ω3 PUFA has an impact on behavioural and cognitive parameters, differently or not from rodents. We address the hypothesis that ω3 PUFA supplementation could lower anxiety and improve cognitive performances of the Grey Mouse Lemur (Microcebus murinus), a nocturnal Malagasy prosimian primate. Adult male mouse lemurs were fed for 5 months on a control diet or on a diet supplemented with long-chain ω3 PUFA (n = 6 per group). Behavioural, cognitive and motor performances were measured using an open field test to evaluate anxiety, a circular platform test to evaluate reference spatial memory, a spontaneous locomotor activity monitoring and a sensory-motor test. ω3-supplemented animals exhibited lower anxiety level compared to control animals, what was accompanied by better performances in a reference spatial memory task (80% of successful trials vs 35% in controls, p<0.05), while the spontaneous locomotor activity was reduced by 31% in ω3-supplemented animals (p<0.001), a parameter that can be linked with lowered anxiety. The long-term dietary ω3 PUFA supplementation positively impacts on anxiety and cognitive performances in the adult mouse lemur. The supplementation of human food with ω3 fatty acids may represent a valuable dietary strategy to improve behavioural and cognitive functions

Effects of Chronic Calorie Restriction or Dietary Resveratrol Supplementation on Insulin Sensitivity Markers in a Primate, Microcebus murinus

The prevalence of diabetes and hyperinsulinemia increases with age, inducing metabolic failure and limiting lifespan. Calorie restriction (CR) without malnutrition delays the aging process, but its long-term application to humans seems difficult. Resveratrol (RSV), a dietary polyphenol, appears to be a promising CR mimetic that can be easily administered in humans. In this work, we hypothesized that both CR and RSV impact insulin sensitivity in a non-human primate compared to standard-fed control (CTL) animals. Four- to five-year-old male grey mouse lemurs (Microcebus murinus) were assigned to three dietary groups: a CTL group, a CR group receiving 30% fewer calories than the CTL and a RSV group receiving the CTL diet supplemented with RSV (200 mg·day−1·kg−1). Insulin sensitivity and glycemia were assessed using an oral glucose tolerance test (OGTT) and the homeostasis model assessment of insulin resistance (HOMA-IR index) evaluation after 21 or 33 months of chronic treatment. Resting metabolic rate was also measured to assess the potential relationships between this energy expenditure parameter and insulin sensitivity markers. No differences were found after a 21-month period of treatment, except for lower glucose levels 30 min after glucose loading in CR animals. After 33 months, CR and RSV decreased glycemia after the oral glucose loading without decreasing fasting blood insulin. A general effect of treatment was observed on the HOMA-IR index, with an 81% reduction in CR animals and 53% in RSV animals after 33 months of treatment compared to CTL. Chronic CR and dietary supplementation with RSV affected insulin sensitivity by improving the glucose tolerance of animals without disturbing their baseline insulin secretion. These results suggest that both CR and RSV have beneficial effects on metabolic alterations, although these effects are different in amplitude between the two anti-aging treatments and potentially rely on different metabolic changes

Synthesis and properties of water-soluble gold colloids covalently derivatized with neutral polymer monolayers

Citrate-capped gold nanoparticles as well as planar gold surfaces can be efficiently grafted with a covalently attached polymer monolayer a few nanometers thick, by simple contact of the metal surface with dilute aqueous solutions of hydrophilic polymers that are end-capped with disulfide moieties, as shown by UV/vis absorption, dynamic light scattering, and surface plasmon resonance studies. The hydrophilic polymer-coated gold colloids can be freeze-dried and stored as powders that can be subsequently dissolved to yield stable aqueous dispersions, even at very large concentrations. They allow for applying filtrations, gel permeation chromatography, or centrifugation. They do not suffer from undesirable nonspecific adsorption of proteins while allowing the diffusion of small species within the hydrogel surface coating. In addition, specific properties of the original hydrophilic polymers are retained such as a lower critical solution temperature. The latter feature could be useful to enhance optical responses of functionalized gold surfaces toward interaction with various substrates

Photoactivation of the CreER T&sup2; recombinase for conditional site-specific recombination with high spatiotemporal resolution.

We implemented a noninvasive optical method for the fast control of Cre recombinase in single cells of a live zebrafish embryo. Optical uncaging of the caged precursor of a nonendogeneous steroid by one- or two-photon illumination was used to restore Cre activity of the CreER(T2) fusion protein in specific target cells. This method labels single cells irreversibly by inducing recombination in an appropriate reporter transgenic animal and thereby can achieve high spatiotemporal resolution in the control of gene expression. This technique could be used more generally to investigate important physiological processes (e.g., in embryogenesis, organ regeneration, or carcinogenesis) with high spatiotemporal resolution (single cell and 10-min scales)

Le nouveau calendrier vaccinal est-il adapté à l’ancien prématuré ?

International audienceThe French 2013 immunization schedule having a goal of simplification with comparable efficacy, has decreased the number of injections and removed the injection performed at three months of age in the general population. Apart from the prevention of invasive pneumococcal infections for which it is recommended to maintain three dose primary immunization, vaccination of premature is not addressed in this new calendar. Can the extremely preterm infants (< 33 weeks of gestational age) benefit from this new schedule or should we keep them in three injections schedule? The objective of this paper is to clarify this point through the data available in the literature. Children born prematurely and especially the “extremely premature” born before 33 weeks are at high risk of infections, some of them are preventable by immunization. Although there is no clinical evidence, for pertussis, pneumococcus, Haemophilus influenzae b, hepatitis B, whatever the immunogenicity criteria, immunogenicity is significantly lower in preterm than in term newborn after 3 doses primary schedule. This lower immunogenicity raises concerns about the transition to two doses, about the ability to give short term protection and booster responses. Given these data, GPIP takes the position for maintaining a primary 3-dose vaccination at 2.3 and 4 months for premature infants less than 33 weeks.Le calendrier vaccinal 2013 répondant à un objectif de simplification à efficacité comparable, a diminué le nombre d’injections recommandées et a en particulier supprimé l’injection effectuée à l’âge de trois mois en population générale. En dehors de la prévention des infections invasives à pneumocoque pour laquelle il est recommandé de maintenir trois doses en primovaccination, la vaccination du prématuré n’est pas abordée dans ce nouveau calendrier. Les grands prématurés peuvent-ils bénéficier de ce nouveau calendrier ou doit-on maintenir chez eux trois injections ? L’objectif de ce travail est de préciser ce point à travers les données disponibles dans la littérature. Les enfants nés prématurément et surtout les « grands prématurés » nés avant 33 SA sont des enfants à haut risque de contracter des infections dont certaines peuvent être prévenues par la vaccination. Pour les valences coqueluche, pneumocoque, Hib, hépatite B quels que soient les critères d’immunogénicité retenus, elle est nettement moins bonne chez les grands prématurés que chez les nouveau-nés à terme. Bien qu’il n’y ait pas de preuve clinique, ceci fait craindre que le passage à deux doses ne permette pas d’une part, de protéger suffisamment à court terme et, d’autre part, laisse craindre une moins bonne réponse immunitaire après le rappel à 11 mois. Compte tenu de ces données, le GPIP prend position pour le maintien d’une primo-vaccination à 3 doses à 2,3 et 4 mois pour les prématurés de moins de 33 semaines