Nicotinamide Phosphoribosyltransferase as a Key Molecule of the Aging/Senescence Process

Aging is a phenomenon underlined by complex molecular and biochemical changes that occur over time. One of the metabolites that is gaining strong research interest is nicotinamide adenine dinucleotide, NAD⁺, whose cellular level has been shown to decrease with age in various tissues of model animals and humans. Administration of NAD⁺ precursors, nicotinamide mononucleotide (NMN) and nicotinamide riboside (NR), to supplement NAD⁺ production through the NAD⁺ salvage pathway has been demonstrated to slow down aging processes in mice. Therefore, NAD⁺ is a critical metabolite now understood to mitigate age-related tissue function decline and prevent age-related diseases in aging animals. In human clinical trials, administration of NAD⁺ precursors to the elderly is being used to address systemic age-associated physiological decline. Among NAD⁺ biosynthesis pathways in mammals, the NAD⁺ salvage pathway is the dominant pathway in most of tissues, and NAMPT is the rate limiting enzyme of this pathway. However, only a few activators of NAMPT, which are supposed to increase NAD⁺, have been developed so far. In this review, we will focus on the importance of NAD⁺ and the possible application of an activator of NAMPT to promote successive aging.     

Electron Holography Studies on Narrow Magnetic Domain Walls Observed in a Heusler Alloy Ni50Mn25Al12.5Ga12.5

Peculiar magnetic domain walls produced in Heusler alloys, which have attracted renewed interest due to their potential application to actuators and spintronic devices, are studied here using electron holography. The observations reveal unexpectedly narrow magnetic domain walls, the width of which showed perfect agreement with that of the antiphase boundaries (APB, e.g., only 3 nm). While the results can be explained by the significant depression of ferromagnetism due to the local chemical disorder, the electron phase shift indicates that ferromagnetic correlation still remains in the APB region.     

Assessment of the antioxidant capacity of a fermented grain food product,Antioxidant Biofactor (AOB), by using pyranine and pyrogallol red as a combined probe

The role of antioxidants contained in foods, beverages, and supplements against oxidative stress has received much attention. The capacity of antioxidants has been assessed by various methods. In this study, the antioxidant capacity of a complex mixture of fermented grains has been assessed by using two probes, pyranine and pyrogallol red (PGR). A supplement commercialised as Antioxidant Biofactor, AOB, was used as a substrate. The extracts from AOB obtained with water and dimethylsulphoxide (DMSO) inhibited the free radical-induced consumption of pyranine and PGR in a concentration-dependent manner. They also suppressed the free radical-induced oxidation of human plasma. It was estimated that 1 g of AOB contained, as Trolox equivalent, roughly 0.13 and 0.24 mmol (2.5 and 4.7 wt%) antioxidants, which could be extracted by water and DMSO, respectively. This study shows that the combination of the above two probes is useful for assessing the total content and activity of antioxidants contained in complex mixtures.     

Antioxidant action of a lipophilic nitroxyl radical,cyclohexane-1-spiro-2′-(4′-oxyimidazolidine-1′-oxyl)-5′-spiro-1″-cyclohexane,against lipid peroxidation under hypoxic conditions

Nitroxyl radicals are known to act as radical scavenging antioxidants. In the present study, a lipophilic nitroxyl radical, cyclohexane-1-spiro-2′-(4′-oxyimidazolidine-1′-oxyl)-5′-spiro-1″-cyclohexane (nitroxyl radical I) was synthesized and its antioxidant capacity was assessed in comparison with a hydrophilic nitroxyl radical, 4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl (Tempol). Both nitroxyl radical I and Tempol inhibited methyl linoleate oxidation induced by free radicals, and the efficacy increased with decreasing partial pressure of oxygen, the effect being more pronounced for nitroxyl radical I than Tempol. Their hydroxylamines inhibited lipid peroxidation more effectively than their corresponding parent nitroxyl radicals. In liposomal membranes, a synergistic effect was observed in the combination of nitroxyl radical I with ascorbic acid, whereas only an additive effect was observed between Tempol and ascorbic acid. The present study suggests that nitroxyl radical I and its hydroxylamine may act as potent antioxidants, especially in combination with ascorbic acid under hypoxic conditions.     

An economic and energy analysis on bio-hydrogen fuel using a gasification process

Recently, in Japan, recycling technologies have been developed using waste biomass material. Waste biomass is traded in the waste materials market between users and a third-party, who receives a fee for processing them. This study is an environmental and economic analysis of a biomass energy system, which can produce hydrogen fuel for fuel cells (purity of 99.99%) as an example of an environmental business model. The experimental apparatus was made based on the moving-bed gasifier by the German company, DM2 Inc., and the hydrogen gas yield was measured. Finally, the economic viability of the future hydrogen business was estimated.The experimental results obtained gave the gas concentration of 57.5% in a Steam/Carbon ratio of 1.40 at 900 °C.Assuming the plant scale of 10 t/d, the production amount of hydrogen gas would be 21.3 kg/h. Based on the law concerning waste processing in Japan, a sizeable amount of waste biomass could be expected. Therefore, if the processing fee which is paid to the group (contractor) ranges between 5.0 and 10.0 $/t, and if the whole investment cost is 6 million dollars and the depreciation period is 15 years, the bio-hydrogen production cost using the experimental data would be 5.75–7.86 $/kg-H₂ without receiving related subsidies. In a one-third grant proportion, the cost would become 4.60–6.72 $/kg-H₂.     

Heterometallic hybrids of homometallic human hemoglobins

Hybridization experiments between normal Hb tetramers (Fe2+ Hb) and those with four metal-substituted hemes (i.e., replacement of Fe2+ by Co2+, Mg2+, Mn2+, Mn3+, Ni2+, or Zn2+) have revealed unexpected behavior. These homometallic Hbs have previously served as models that mimic the deoxy or oxy properties of normal Fe2+ Hb. In this study, hybrids were composed of one alpha 1 beta 1 dimer that is metal-substituted at both hemes, in association with a second dimer alpha 2 beta 2 that has normal Fe2+ hemes. Both metal-substituted subunits are unligated, whereas the two Fe2+ subunits either are both unligated or both ligated with O2, CO, or CN. It was found that four of the metal-substituted Hbs (Mg2+ Hb, Mn2+ Hb, Ni2+ Hb, and Zn2+ Hb) did not form detectable amounts of heterometallic hybrids with normal Fe2+ Hb even though (i) their homometallic parents formed tight tetrameric complexes with stabilities similar to that of Fe2+ Hb and (ii) hybrids with metal substitution at both alpha sites or both beta sites are known to form readily. This striking positional effect was independent of whether the normal Fe2+ hemes were ligated and of which ligand was used. These findings indicate that surprisingly large changes in tetramer behavior can arise from small and subtle perturbations at the heme sites. Possible origins of these effects are considered.     

Evaluation of Lipophilic Antioxidant Efficacy in Vivo by the Biomarkers Hydroxyoctadecadienoic Acid and Isoprostane

The evaluation of antioxidant activity in vivo is difficult. In this study, the effects of dietary natural and synthetic antioxidants on the lipid peroxidation in mice were assessed using a biomarker, total hydroxyoctadecadienoic acid (tHODE). Biological samples such as plasma, erythrocytes, and tissues were first reduced and then saponified to convert various oxidation products of linoleates to tHODE. Subsequently, the absolute concentration of tHODE and its stereoisomer ratio, [9- and 13-(Z,E)-HODE)/[9- and 13-(E,E)-HODE], which is a measure of the hydrogen donor capacity of antioxidants, were determined by gas chromatography–mass spectrometry (GC–MS) analyses. These were then compared with total 8-iso-prostaglandin F_2α (t8-iso-PGF_2α) which was also assessed after reduction and saponification. Remarkable increases in tHODE and t8-iso-PGF_2α levels were observed in the plasma, erythrocytes, liver, and brain of mice that were fed an α-tocopherol (αT)-stripped (E-free) diet for 1 month when compared with those of mice that were fed a standard diet (αT = 0.002 wt%). When mice were fed for 1 month on an E-free diet supplemented with a lipophilic antioxidant (0.04 wt%), namely, αT, α-tocotrienol (αT3), γ-tocopherol (γT), or 2,3-dihydro-5-hydroxy-4,6-di-tert-butyl-2,2-dipentylbenzofuran (BO-653), a potent synthetic antioxidant, the increases of tHODE and t8-iso-PGF_2α in the plasma, erythrocytes, liver, and brain were suppressed to the levels lower than those of mice fed a standard diet. The (Z,E/E,E) HODE ratio was decreased in the plasma and erythrocytes of mice fed the E-free diet when compared with that in mice fed the standard diet. This stereo-isomeric ratio was significantly recovered by the addition of αT and BO-653. These results show that the tHODE level and the (Z,E/E,E) HODE ratio are useful biomarkers for the assessment of antioxidant capacity in vivo and that the antioxidant capacity decreased in the order: BO-653 > αT3 ≧ αT, γT, as assessed by tHODE levels from blood, liver, and brain.     

Identification of enzyme responsible for erythritol utilization and reaction product in yeast Lipomyces starkeyi

We have identified the enzyme responsible for erythritol utilization and its reaction product in the yeast Lipomyces starkeyi CBS 1807. The enzyme, a polyol dehydrogenase requiring NAD+ as a coenzyme, was induced by erythritol in this yeast. We confirmed that the enzyme product was L-erythrulose by MS, NMR, and polarimeter analyses, meaning that we clarified the first step of erythritol utilization in yeasts for the first time. In the case of the oxidative reaction, D-threitol, (2R,3R)-2,3-butanediol, and erythritol were much better substrates than 21 other polyols tested. These three substrates are tetroses and have an R configuration at C-3, and whose third carbon results in easiest oxidation in this enzyme. The research of the substrate specificity in the reductive reaction demonstrated that L-erythrulose and dihydroxyacetone were better substrates, that D-acetoin was inactive and L-erythrose (aldose) was slightly active.