scholarly journals Effect of Methionine Restriction on Aging: Its Relationship to Oxidative Stress

Biomedicines ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 130
Author(s):  
Munehiro Kitada ◽  
Yoshio Ogura ◽  
Itaru Monno ◽  
Jing Xu ◽  
Daisuke Koya
Keyword(s):  
Oxidative Stress ◽  
Metabolic Health ◽  
Polyamine Metabolism ◽  
Lifespan Extension ◽  
Methionine Metabolism ◽  
Glutathione Synthesis ◽  
Methyl Donors ◽  
Methionine Restriction ◽  
Adenosyl Methionine ◽  
Species Production

Enhanced oxidative stress is closely related to aging and impaired metabolic health and is influenced by diet-derived nutrients and energy. Recent studies have shown that methionine restriction (MetR) is related to longevity and metabolic health in organisms from yeast to rodents. The effect of MetR on lifespan extension and metabolic health is mediated partially through a reduction in oxidative stress. Methionine metabolism is involved in the supply of methyl donors such as S-adenosyl-methionine (SAM), glutathione synthesis and polyamine metabolism. SAM, a methionine metabolite, activates mechanistic target of rapamycin complex 1 and suppresses autophagy; therefore, MetR can induce autophagy. In the process of glutathione synthesis in methionine metabolism, hydrogen sulfide (H2S) is produced through cystathionine-β-synthase and cystathionine-γ-lyase; however, MetR can induce increased H2S production through this pathway. Similarly, MetR can increase the production of polyamines such as spermidine, which are involved in autophagy. In addition, MetR decreases oxidative stress by inhibiting reactive oxygen species production in mitochondria. Thus, MetR can attenuate oxidative stress through multiple mechanisms, consequently associating with lifespan extension and metabolic health. In this review, we summarize the current understanding of the effects of MetR on lifespan extension and metabolic health, focusing on the reduction in oxidative stress.

scholarly journals Perspective: Methionine Restriction–Induced Longevity—A Possible Role for Inhibiting the Synthesis of Bacterial Quorum Sensing Molecules

2020 ◽  
Vol 11 (4) ◽  
pp. 773-783
Author(s):  
Peng Bin ◽  
Congrui Zhu ◽  
Shaojuan Liu ◽  
Zhendong Li ◽  
Wenkai Ren ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Quorum Sensing ◽  
Stress Resistance ◽  
Lifespan Extension ◽  
Oxidative Stress Resistance ◽  
Methionine Restriction ◽  
Igf I ◽  
Bacterial Quorum Sensing ◽  
Bacterial Quorum ◽  
Multiple Species

ABSTRACT Methionine restriction (MR) extends lifespans in multiple species through mechanisms that include enhanced oxidative stress resistance and inhibition of insulin/insulin-like growth factor I (IGF-I) signaling. Methionine and S-adenosylmethionine (SAM) are the essential precursors of bacterial quorum sensing (QS) molecules, and therefore, MR might also affect bacterial communication to prevent enteric bacterial infection as well as chronic inflammation, which contributes to lifespan prolongation. Here, we discuss the influence of MR on oxidative stress resistance and inhibition of insulin/IGF-I cell signaling and further propose a potential mechanism involving bacterial QS inhibition for lifespan extension. Unraveling the connection between MR and inhibition of QS provides new strategies for combating infectious diseases, resulting in enriched understanding of MR-induced lifespan extension.

scholarly journals Methionine restriction plus overload improves skeletal muscle and metabolic health in old mice on a high fat diet

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Anandini Swaminathan ◽  
Andrej Fokin ◽  
Tomas Venckūnas ◽  
Hans Degens
Keyword(s):  
Skeletal Muscle ◽  
Glucose Tolerance ◽  
Muscle Mass ◽  
Body Mass ◽  
High Fat Diet ◽  
Control Diet ◽  
Metabolic Health ◽  
High Fat ◽  
Methionine Restriction ◽  
Old Mice

AbstractMethionine restriction (MR) has been shown to reduce the age-induced inflammation. We examined the effect of MR (0.17% methionine, 10% kCal fat) and MR + high fat diet (HFD) (0.17% methionine, 45% kCal fat) on body mass, food intake, glucose tolerance, resting energy expenditure, hind limb muscle mass, denervation-induced atrophy and overload-induced hypertrophy in young and old mice. In old mice, MR and MR + HFD induced a decrease in body mass. Muscle mass per body mass was lower in old compared to young mice. MR restored some of the HFD-induced reduction in muscle oxidative capacity. The denervation-induced atrophy of the m. gastrocnemius was larger in animals on MR than on a control diet, irrespective of age. Old mice on MR had larger hypertrophy of m. plantaris. Irrespective of age, MR and MR + HFD had better glucose tolerance compared to the other groups. Young and old mice on MR + HFD had a higher resting VO2 per body mass than HFD group. Mice on MR and MR + HFD had a resting respiratory quotient closer to 0.70, irrespective of age, indicating an increased utilization of lipids. In conclusion, MR in combination with resistance training may improve skeletal muscle and metabolic health in old age even in the face of obesity.

scholarly journals Nicotinamide Nucleotide Transhydrogenase as a Novel Treatment Target in Adrenocortical Carcinoma

Endocrinology ◽  
2018 ◽  
Vol 159 (8) ◽  
pp. 2836-2849 ◽  
Author(s):  
Vasileios Chortis ◽  
Angela E Taylor ◽  
Craig L Doig ◽  
Mark D Walsh ◽  
Eirini Meimaridou ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Adrenocortical Carcinoma ◽  
Reduced Form ◽  
Polyamine Metabolism ◽  
Metabolome Analysis ◽  
Nucleotide Synthesis ◽  
Treatment Target ◽  
Nicotinamide Nucleotide Transhydrogenase ◽  
Response To Chemotherapy

Abstract Adrenocortical carcinoma (ACC) is an aggressive malignancy with poor response to chemotherapy. In this study, we evaluated a potential new treatment target for ACC, focusing on the mitochondrial reduced form of NAD phosphate (NADPH) generator nicotinamide nucleotide transhydrogenase (NNT). NNT has a central role within mitochondrial antioxidant pathways, protecting cells from oxidative stress. Inactivating human NNT mutations result in congenital adrenal insufficiency. We hypothesized that NNT silencing in ACC cells will induce toxic levels of oxidative stress. To explore this, we transiently knocked down NNT in NCI-H295R ACC cells. As predicted, this manipulation increased intracellular levels of oxidative stress; this resulted in a pronounced suppression of cell proliferation and higher apoptotic rates, as well as sensitization of cells to chemically induced oxidative stress. Steroidogenesis was paradoxically stimulated by NNT loss, as demonstrated by mass spectrometry–based steroid profiling. Next, we generated a stable NNT knockdown model in the same cell line to investigate the longer lasting effects of NNT silencing. After long-term culture, cells adapted metabolically to chronic NNT knockdown, restoring their redox balance and resilience to oxidative stress, although their proliferation remained suppressed. This was associated with higher rates of oxygen consumption. The molecular pathways underpinning these responses were explored in detail by RNA sequencing and nontargeted metabolome analysis, revealing major alterations in nucleotide synthesis, protein folding, and polyamine metabolism. This study provides preclinical evidence of the therapeutic merit of antioxidant targeting in ACC as well as illuminating the long-term adaptive response of cells to oxidative stress.

scholarly journals Regulation of intracellular glutathione levels in erythrocytes infected with chloroquine-sensitive and chloroquine-resistant Plasmodium falciparum

2002 ◽  
Vol 368 (3) ◽  
pp. 761-768 ◽  
Author(s):  
Svenja MEIERJOHANN ◽  
Rolf D. WALTER ◽  
Sylke MÜLLER
Keyword(s):  
Oxidative Stress ◽  
Red Blood Cells ◽  
Blood Cells ◽  
Differential Susceptibility ◽  
Protozoan Parasite ◽  
Chloroquine Resistance ◽  
Glutathione Metabolism ◽  
Glutathione Synthesis ◽  
Intracellular Glutathione ◽  
Glutamylcysteine Synthetase

Malaria is one of the most devastating tropical diseases despite the availability of numerous drugs acting against the protozoan parasite Plasmodium in its human host. However, the development of drug resistance renders most of the existing drugs useless. In the malaria parasite the tripeptide glutathione is not only involved in maintaining an adequate intracellular redox environment and protecting the cell against oxidative stress, but it has also been shown that it degrades non-polymerized ferriprotoporphyrin IX (FP IX) and is thus implicated in the development of chloroquine resistance. Glutathione levels in Plasmodium-infected red blood cells are regulated by glutathione synthesis, glutathione reduction and glutathione efflux. Therefore the effects of drugs that interfere with these metabolic processes were studied to establish possible differences in the regulation of the glutathione metabolism of a chloroquine-sensitive and a chloroquine-resistant strain of Plasmodiumfalciparum. Growth inhibition of P. falciparum 3D7 by d,l-buthionine-(S,R)sulphoximine (BSO), an inhibitor of γ-glutamylcysteine synthetase (γ-GCS), and by Methylene Blue (MB), an inhibitor of gluta thione reductase (GR), was significantly more pronounced than inhibition of P.falciparum Dd2 growth by these drugs. These results correlate with the higher levels of total glutathione in P. falciparum Dd2. Short-term incubations of Percoll-enriched trophozoite-infected red blood cells in the presence of BSO, MB and N,N1-bis(2-chloroethyl)-N-nitrosourea and subsequent determinations of γ-GCS activities, GR activities and glutathione disulphide efflux revealed that maintenance of intracellular glutathione in P. falciparum Dd2 is mainly dependent on glutathione synthesis whereas in P. falciparum 3D7 it is regulated via GR. Generally, P. falciparum Dd2 appears to be able to sustain its intracellular glutathione more efficiently than P. falciparum 3D7. In agreement with these findings is the differential susceptibility to oxidative stress of both parasite strains elicited by the glucose/glucose oxidase system.

scholarly journals Menadione effect on l-cysteine desulfuration in U373 cells.

2007 ◽  
Vol 54 (2) ◽  
pp. 407-411 ◽  
Author(s):  
Maria Wróbel ◽  
Halina Jurkowska
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Control Culture ◽  
Oxygen Species ◽  
Active Centers ◽  
Glutathione Synthesis ◽  
Sulfane Sulfur ◽  
Mercaptopyruvate Sulfurtransferase ◽  
Sulfur Level ◽  
U373 Cells

The non-cytotoxic concentration (20 microM) of menadione (2-methyl-1,4-naphthoquinone), after 1 h of incubation, leads to loss of the activity of rhodanese by 33%, 3-mercaptopyruvate sulfurtransferase by 20%, as well as the level of sulfane sulfur by about 23% and glutathione by 12%, in the culture of U373 cells, in comparison with the control culture. Reactive oxygen species generated by menadione oxidize sulfhydryl groups in active centers of the investigated enzymes, inhibiting them and saving cysteine for glutathione synthesis. A decreased sulfane sulfur level can be correlated with an oxidative stress.

Effect of Maternal Betaine Supplementation on Growth, Plane of Nutrition, Blood Biochemical Profile and Antioxidant Status of Progeny Pigs

2021 ◽  
Author(s):  
Alok Mishra ◽  
A.K. Verma ◽  
Asit Das ◽  
Putan Singh ◽  
V.K. Munde
Keyword(s):  
Oxidative Stress ◽  
Serum Concentration ◽  
Antioxidant Status ◽  
Late Pregnancy ◽  
Methyl Donors ◽  
Blood Biochemical ◽  
Growth Plane ◽  
Best Response ◽  
Betaine Supplementation ◽  
Length Of Gestation

Background: Dietary supplementation of methyl donors like vitamins B9, B12, choline and betaine have been reported to reduce oxidative stress not only in sows but can also reduce oxidative stress in offspring through epigenetic modulation of DNA. However, cell proliferation and fetal development and oxidative stress associated with it is not uniform during the whole length of gestation. Hence this experiment was conducted to study the effects of maternal betaine supplementation on growth, plane of nutrition and antioxidant profile of progeny pigs.Methods: Eighteen crossbred (Landrace X Desi) sows were randomly distributed into three groups of six each in an experiment based on completely randomized design (CRD). The sows in control (T0) were fed standard ration to meet their requirements. Supplementary betaine at 3 g/kg DM were provided either during late pregnancy (d 76 onwards till parturition) only or throughout the length of gestation to the sows of groups T1 and T2, respectively. The samples of feed offered, residue and faeces were analyzed for proximate principles following the standard procedures. Blood samples from the progeny piglets were collected and antioxidant status of the piglets assessed by the measurement of superoxide dismutase (SOD) and catalase (CAT) by using standard kits.Result: The serum concentration of SOD was comparable (p greater than 0.05) among the groups, whereas serum concentration of catalase was higher (p less than 0.05) in piglets born to the dam exposed to supplementary beanie during gestation, the best response was observed whilst betaine was supplemented in the maternal diets during the whole length of gestation It was concluded that supplementation of betaine at 3g/kg in the diet of pregnant sows improved the antioxidant capacity of piglets borne to them.

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