Calorie Restriction-Mediated Replicative Lifespan Extension in Yeast Is Non-Cell Autonomous

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Mei, Szu-Chieh; Brenner, Charles

2015-01-01

In laboratory yeast strains with Sir2 and Fob1 function, wild-type NAD+ salvage is required for calorie restriction (CR) to extend replicative lifespan. CR does not significantly alter steady state levels of intracellular NAD+ metabolites. However, levels of Sir2 and Pnc1, two enzymes that sequentially convert NAD+ to nicotinic acid (NA), are up-regulated during CR. To test whether factors such as NA might be exported by glucose-restricted mother cells to survive later generations, we developed a replicative longevity paradigm in which mother cells are moved after 15 generations on defined media. The experiment reveals that CR mother cells lose the longevity benefit of CR when evacuated from their local environment to fresh CR media. Addition of NA or nicotinamide riboside (NR) allows a moved mother to maintain replicative longevity despite the move. Moreover, conditioned medium from CR-treated cells transmits the longevity benefit of CR to moved mother cells. Evidence suggests the existence of a longevity factor that is dialyzable but is neither NA nor NR, and indicates that Sir2 is not required for the longevity factor to be produced or to act. Data indicate that the benefit of glucose-restriction is transmitted from cell to cell in budding yeast, suggesting that glucose restriction may benefit neighboring cells and not only an individual cell. PMID:25633578

Calorie restriction-mediated replicative lifespan extension in yeast is non-cell autonomous.

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Szu-Chieh Mei

2015-01-01

Full Text Available In laboratory yeast strains with Sir2 and Fob1 function, wild-type NAD+ salvage is required for calorie restriction (CR to extend replicative lifespan. CR does not significantly alter steady state levels of intracellular NAD+ metabolites. However, levels of Sir2 and Pnc1, two enzymes that sequentially convert NAD+ to nicotinic acid (NA, are up-regulated during CR. To test whether factors such as NA might be exported by glucose-restricted mother cells to survive later generations, we developed a replicative longevity paradigm in which mother cells are moved after 15 generations on defined media. The experiment reveals that CR mother cells lose the longevity benefit of CR when evacuated from their local environment to fresh CR media. Addition of NA or nicotinamide riboside (NR allows a moved mother to maintain replicative longevity despite the move. Moreover, conditioned medium from CR-treated cells transmits the longevity benefit of CR to moved mother cells. Evidence suggests the existence of a longevity factor that is dialyzable but is neither NA nor NR, and indicates that Sir2 is not required for the longevity factor to be produced or to act. Data indicate that the benefit of glucose-restriction is transmitted from cell to cell in budding yeast, suggesting that glucose restriction may benefit neighboring cells and not only an individual cell.

MSN2 and MSN4 link calorie restriction and TOR to sirtuin-mediated lifespan extension in Saccharomyces cerevisiae.

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Oliver Medvedik

2007-10-01

Full Text Available Calorie restriction (CR robustly extends the lifespan of numerous species. In the yeast Saccharomyces cerevisiae, CR has been proposed to extend lifespan by boosting the activity of sirtuin deacetylases, thereby suppressing the formation of toxic repetitive ribosomal DNA (rDNA circles. An alternative theory is that CR works by suppressing the TOR (target of rapamycin signaling pathway, which extends lifespan via mechanisms that are unknown but thought to be independent of sirtuins. Here we show that TOR inhibition extends lifespan by the same mechanism as CR: by increasing Sir2p activity and stabilizing the rDNA locus. Further, we show that rDNA stabilization and lifespan extension by both CR and TOR signaling is due to the relocalization of the transcription factors Msn2p and Msn4p from the cytoplasm to the nucleus, where they increase expression of the nicotinamidase gene PNC1. These findings suggest that TOR and sirtuins may be part of the same longevity pathway in higher organisms, and that they may promote genomic stability during aging.

Nicotinamide and PNC1 govern lifespan extension by calorie restriction in Saccharomyces cerevisiae.

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Anderson, Rozalyn M; Bitterman, Kevin J; Wood, Jason G; Medvedik, Oliver; Sinclair, David A

2003-05-08

Calorie restriction extends lifespan in a broad range of organisms, from yeasts to mammals. Numerous hypotheses have been proposed to explain this phenomenon, including decreased oxidative damage and altered energy metabolism. In Saccharomyces cerevisiae, lifespan extension by calorie restriction requires the NAD+-dependent histone deacetylase, Sir2 (ref. 1). We have recently shown that Sir2 and its closest human homologue SIRT1, a p53 deacetylase, are strongly inhibited by the vitamin B3 precursor nicotinamide. Here we show that increased expression of PNC1 (pyrazinamidase/nicotinamidase 1), which encodes an enzyme that deaminates nicotinamide, is both necessary and sufficient for lifespan extension by calorie restriction and low-intensity stress. We also identify PNC1 as a longevity gene that is responsive to all stimuli that extend lifespan. We provide evidence that nicotinamide depletion is sufficient to activate Sir2 and that this is the mechanism by which PNC1 regulates longevity. We conclude that yeast lifespan extension by calorie restriction is the consequence of an active cellular response to a low-intensity stress and speculate that nicotinamide might regulate critical cellular processes in higher organisms.

New genes tied to endocrine, metabolic, and dietary regulation of lifespan from a Caenorhabditis elegans genomic RNAi screen.

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Malene Hansen

2005-07-01

Full Text Available Most of our knowledge about the regulation of aging comes from mutants originally isolated for other phenotypes. To ask whether our current view of aging has been affected by selection bias, and to deepen our understanding of known longevity pathways, we screened a genomic Caenorhabditis elegans RNAi library for clones that extend lifespan. We identified 23 new longevity genes affecting signal transduction, the stress response, gene expression, and metabolism and assigned these genes to specific longevity pathways. Our most important findings are (i that dietary restriction extends C. elegans' lifespan by down-regulating expression of key genes, including a gene required for methylation of many macromolecules, (ii that integrin signaling is likely to play a general, evolutionarily conserved role in lifespan regulation, and (iii that specific lipophilic hormones may influence lifespan in a DAF-16/FOXO-dependent fashion. Surprisingly, of the new genes that have conserved sequence domains, only one could not be associated with a known longevity pathway. Thus, our current view of the genetics of aging has probably not been distorted substantially by selection bias.

New Genes Tied to Endocrine, Metabolic, and Dietary Regulation of Lifespan from a Caenorhabditis elegans Genomic RNAi Screen.

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2005-07-01

Full Text Available Most of our knowledge about the regulation of aging comes from mutants originally isolated for other phenotypes. To ask whether our current view of aging has been affected by selection bias, and to deepen our understanding of known longevity pathways, we screened a genomic Caenorhabditis elegans RNAi library for clones that extend lifespan. We identified 23 new longevity genes affecting signal transduction, the stress response, gene expression, and metabolism and assigned these genes to specific longevity pathways. Our most important findings are (i that dietary restriction extends C. elegans' lifespan by down-regulating expression of key genes, including a gene required for methylation of many macromolecules, (ii that integrin signaling is likely to play a general, evolutionarily conserved role in lifespan regulation, and (iii that specific lipophilic hormones may influence lifespan in a DAF-16/FOXO-dependent fashion. Surprisingly, of the new genes that have conserved sequence domains, only one could not be associated with a known longevity pathway. Thus, our current view of the genetics of aging has probably not been distorted substantially by selection bias.

Short-term dietary restriction and fasting precondition against ischemia reperfusion injury in mice.

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Mitchell, James R; Verweij, Mariëlle; Brand, Karl; van de Ven, Marieke; Goemaere, Natascha; van den Engel, Sandra; Chu, Timothy; Forrer, Flavio; Müller, Cristina; de Jong, Marion; van IJcken, Wilfred; IJzermans, Jan N M; Hoeijmakers, Jan H J; de Bruin, Ron W F

2010-02-01

Dietary restriction (DR) extends lifespan and increases resistance to multiple forms of stress, including ischemia reperfusion injury to the brain and heart in rodents. While maximal effects on lifespan require long-term restriction, the kinetics of onset of benefits against acute stress is not known. Here, we show that 2-4 weeks of 30% DR improved survival and kidney function following renal ischemia reperfusion injury in mice. Brief periods of water-only fasting were similarly effective at protecting against ischemic damage. Significant protection occurred within 1 day, persisted for several days beyond the fasting period and extended to another organ, the liver. Protection by both short-term DR and fasting correlated with improved insulin sensitivity, increased expression of markers of antioxidant defense and reduced expression of markers of inflammation and insulin/insulin-like growth factor-1 signaling. Unbiased transcriptional profiling of kidneys from mice subject to short-term DR or fasting revealed a significant enrichment of signature genes of long-term DR. These data demonstrate that brief periods of reduced food intake, including short-term daily restriction and fasting, can increase resistance to ischemia reperfusion injury in rodents and suggest a rapid onset of benefits of DR in mammals.

Sorbitol treatment extends lifespan and induces the osmotic stress response in Caenorhabditis elegans

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Devon eChandler-Brown

2015-10-01

Full Text Available The response to osmotic stress is a highly conserved process for adapting to changing environmental conditions. Prior studies have shown that hyperosmolarity by addition of sorbitol to the growth medium is sufficient to increase both chronological and replicative lifespan in the budding yeast, Saccharomyces cerevisiae. Here we report a similar phenomenon in the nematode Caenorhabditis elegans. Addition of sorbitol to the nematode growth medium induces an adaptive osmotic response and increases C. elegans lifespan by about 35%. Lifespan extension from 5% sorbitol behaves similarly to dietary restriction in a variety of genetic backgrounds, increasing lifespan additively with mutation of daf-2(e1370 and independently of daf-16(mu86, sir-2.1(ok434, aak-2(ok524, and hif-1(ia04. Dietary restriction by bacterial deprivation or mutation of eat-2(ad1113 fails to further extend lifespan in the presence of 5% sorbitol. Two mutants with constitutive activation of the osmotic response, osm-5(p813 and osm-7(n1515, were found to be long-lived, and lifespan extension from sorbitol required the glycerol biosynthetic enzymes GPDH-1 and GPDH-2. Taken together, these observations demonstrate that exposure to sorbitol at levels sufficient to induce an adaptive osmotic response extends lifespan in worms and define the osmotic stress response pathway as a longevity pathway conserved between yeast and nematodes.

On the genetic mechanisms of nutrient-dependent lifespan and reproduction

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Zandveld, Jelle

2017-01-01

Dietary restriction (DR), a moderate reduction in nutrient intake, improves health or extends lifespan across many species. Moreover, recent insights have shown that also the effects of specific nutrients are of importance for the beneficial effects of DR rather than intake alone. However, we

Effects of dietary restriction on adipose mass and biomarkers of healthy aging in human.

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Lettieri-Barbato, Daniele; Giovannetti, Esmeralda; Aquilano, Katia

2016-11-29

In developing countries the rise of obesity and obesity-related metabolic disorders, such as cardiovascular diseases and type 2 diabetes, reflects the changes in lifestyle habits and wrong dietary choices. Dietary restriction (DR) regimens have been shown to extend health span and lifespan in many animal models including primates. Identifying biomarkers predictive of clinical benefits of treatment is one of the primary goals of precision medicine. To monitor the clinical outcomes of DR interventions in humans, several biomarkers are commonly adopted. However, a validated link between the behaviors of such biomarkers and DR effects is lacking at present time. Through a systematic analysis of human intervention studies, we evaluated the effect size of DR (i.e. calorie restriction, very low calorie diet, intermittent fasting, alternate day fasting) on health-related biomarkers. We found that DR is effective in reducing total and visceral adipose mass and improving inflammatory cytokines profile and adiponectin/leptin ratio. By analysing the levels of canonical biomarkers of healthy aging, we also validated the changes of insulin, IGF-1 and IGFBP-1,2 to monitor DR effects. Collectively, we developed a useful platform to evaluate the human responses to dietary regimens low in calories.

Dietary restriction of rodents decreases aging rate without affecting initial mortality rate -- a meta-analysis.

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Simons, Mirre J P; Koch, Wouter; Verhulst, Simon

2013-06-01

Dietary restriction (DR) extends lifespan in multiple species from various taxa. This effect can arise via two distinct but not mutually exclusive ways: a change in aging rate and/or vulnerability to the aging process (i.e. initial mortality rate). When DR affects vulnerability, this lowers mortality instantly, whereas a change in aging rate will gradually lower mortality risk over time. Unraveling how DR extends lifespan is of interest because it may guide toward understanding the mechanism(s) mediating lifespan extension and also has practical implications for the application of DR. We reanalyzed published survival data from 82 pairs of survival curves from DR experiments in rats and mice by fitting Gompertz and also Gompertz-Makeham models. The addition of the Makeham parameter has been reported to improve the estimation of Gompertz parameters. Both models separate initial mortality rate (vulnerability) from an age-dependent increase in mortality (aging rate). We subjected the obtained Gompertz parameters to a meta-analysis. We find that DR reduced aging rate without affecting vulnerability. The latter contrasts with the conclusion of a recent analysis of a largely overlapping data set, and we show how the earlier finding is due to a statistical artifact. Our analysis indicates that the biology underlying the life-extending effect of DR in rodents likely involves attenuated accumulation of damage, which contrasts with the acute effect of DR on mortality reported for Drosophila. Moreover, our findings show that the often-reported correlation between aging rate and vulnerability does not constrain changing aging rate without affecting vulnerability simultaneously. © 2013 John Wiley & Sons Ltd and the Anatomical Society.

Sulfur restriction extends fission yeast chronological lifespan through Ecl1 family genes by downregulation of ribosome.

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Ohtsuka, Hokuto; Takinami, Masahiro; Shimasaki, Takafumi; Hibi, Takahide; Murakami, Hiroshi; Aiba, Hirofumi

2017-07-01

Nutritional restrictions such as calorie restrictions are known to increase the lifespan of various organisms. Here, we found that a restriction of sulfur extended the chronological lifespan (CLS) of the fission yeast Schizosaccharomyces pombe. The restriction decreased cellular size, RNA content, and ribosomal proteins and increased sporulation rate. These responses depended on Ecl1 family genes, the overexpression of which results in the extension of CLS. We also showed that the Zip1 transcription factor results in the sulfur restriction-dependent expression of the ecl1 + gene. We demonstrated that a decrease in ribosomal activity results in the extension of CLS. Based on these observations, we propose that sulfur restriction extends CLS through Ecl1 family genes in a ribosomal activity-dependent manner. © 2017 John Wiley & Sons Ltd.

Strong dietary restrictions protect Drosophila against anoxia/reoxygenation injuries.

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Paul Vigne

Full Text Available Reoxygenation of ischemic tissues is a major factor that determines the severity of cardiovascular diseases. This paper describes the consequences of anoxia/reoxygenation (A/R stresses on Drosophila, a useful, anoxia tolerant, model organism.Newly emerged adult male flies were exposed to anoxic conditions (<1% O2 for 1 to 6 hours, reoxygenated and their survival was monitored.A/R stresses induced a transient increase in mortality which peaked at the time of reoxygenation. Then flies recovered low mortality rates similar to those of control flies. A/R induced mortality was strongly dependent on dietary conditions during the 48 h that preceded anoxia. Well fed flies were anoxia sensitive. Strong dietary restrictions and starvation conditions protected flies against A/R injuries. The tolerance to anoxia was associated to large decreases in glycogen, protein, and ATP contents. During anoxia, anoxia tolerant flies produced more lactate, less phosphate and they maintained more stable ATP levels than anoxia sensitive flies. Moderate dietary restrictions, which increased the longevity of normoxic flies, did not promote resistance to A/R stresses. Diet dependent A/R injuries were still observed in sigma loss of function mutants and they were insensitive to dietary rapamycin or resveratrol. AICAR (5-aminoimidazole-4-carboxamide-1-beta-D-ribose-furanoside, an activator AMP kinase decreased A/R injuries. Mutants in the insulin signalling pathway were more anoxia tolerant in a fed state.Long A/R stresses induce a transient increase in mortality in Drosophila. This mortality is highly dependent on dietary conditions prior to the stress. Strong dietary restrictions and starvation conditions protect flies against A/R injuries, probably by inducing a major remodelling of energy metabolism. The results also indicate that mechanistically different responses develop in response to dietary restrictions of different strengths. AMP kinase and the insulin signalling

Starving for life: what animal studies can and cannot tell us about the use of caloric restriction to prolong human lifespan.

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Speakman, John R; Hambly, Catherine

2007-04-01

Caloric restriction (CR) is the only experimental nongenetic paradigm known to increase lifespan. It has broad applicability and extends the life of most species through a retardation of aging. There is considerable interest in the use of CR in humans, and animal studies can potentially tell us about the impacts. In this article we highlight some of the things that animal studies can tell us about CR in humans. Rodent studies indicate that the benefits of CR on lifespan extension are related to the extent of restriction. The benefits of CR, however, decline as the age of onset of treatment is delayed. Modeling these impacts suggests that if a 48-y-old man engaged in 30% CR until his normal life expectancy of 78, he might increase his life expectancy by 2.8 y. Exercise and cold exposure induce similar energy deficits, but animals respond to these energy deficits in different ways that have a minor impact on lifespan. Measurements of animal responses when they cease restriction indicate that prolonged CR does not diminish hunger, even though the animals may have been in long-term energy balance. Neuroendocrine profiles support the idea that animals under CR are continuously hungry. The feasibility of restricting intake in humans for many decades without long-term support is questionable. However, what is unclear from animal studies is whether taking drugs that suppress appetite will generate the same impact on longevity or whether the neuroendocrine correlates of hunger play an integral role in mediating CRs effects.

Altered bacterial metabolism, not coenzyme Q content, is responsible for the lifespan extension in Caenorhabditis elegans fed an Escherichia coli diet lacking coenzyme Q.

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Saiki, Ryoichi; Lunceford, Adam L; Bixler, Tarra; Dang, Peter; Lee, Wendy; Furukawa, Satoru; Larsen, Pamela L; Clarke, Catherine F

2008-06-01

Coenzyme Q(n) is a fully substituted benzoquinone containing a polyisoprene tail of distinct numbers (n) of isoprene groups. Caenorhabditis elegans fed Escherichia coli devoid of Q(8) have a significant lifespan extension when compared to C. elegans fed a standard 'Q-replete'E. coli diet. Here we examine possible mechanisms for the lifespan extension caused by the Q-less E. coli diet. A bioassay for Q uptake shows that a water-soluble formulation of Q(10) is effectively taken up by both clk-1 mutant and wild-type nematodes, but does not reverse lifespan extension mediated by the Q-less E. coli diet, indicating that lifespan extension is not due to the absence of dietary Q per se. The enhanced longevity mediated by the Q-less E. coli diet cannot be attributed to dietary restriction, different Qn isoforms, reduced pathogenesis or slowed growth of the Q-less E. coli, and in fact requires E. coli viability. Q-less E. coli have defects in respiratory metabolism. C. elegans fed Q-replete E. coli mutants with similarly impaired respiratory metabolism due to defects in complex V also show a pronounced lifespan extension, although not as dramatic as those fed the respiratory deficient Q-less E. coli diet. The data suggest that feeding respiratory incompetent E. coli, whether Q-less or Q-replete, produces a robust life extension in wild-type C. elegans. We believe that the fermentation-based metabolism of the E. coli diet is an important parameter of C. elegans longevity.

Does SIRT-1 Mediate Calorie Restriction and Prolong Life? – A Mini Review

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Kordala Anna

2014-09-01

Full Text Available Calorie restriction is the only intervention proved to prolong both average and maximum lifespan in yeast, worms, fish, rodents and possibly primates. Not only does the regimen prolong life, but it also reduces the incident of numerous age-related diseases like diabetes, atherosclerosis or cancer and slows down ageing. Mechanisms by which that is thought to occur have not yet been elucidated, but they probably involve reactive oxygen species signaling, insulin growth factor and transcriptional factors. Here, special emphasis is given to SIRT1 - silent information regulator. There is sound evidence showing that SIRT1 is a key player in mediating physiological response to calorie restriction and that its overexpression is correlated with extended lifespan. The possible mechanism leading to its elevated levels is high NAD/NADH ratio, observed in Sir2 in yeast. SIRT1 increases glucose production, enhances fat mobilization, stimulates angiogenesis, prevents neuronal degeneration and rises insulin sensitivity. Therefore, it seems to be a very beneficial factor activated by such a simple intervention that is calorie restriction.

Dietary sodium restriction: a neglected therapeutic opportunity in chronic kidney disease

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Humalda, Jelmer K.; Navis, Gerjan

2014-01-01

Purpose of review Restriction of dietary sodium is recommended at a population level as well as for groups at high cardiovascular risk, and chronic kidney disease (CKD). This review addresses recent evidence for the protective effect of dietary sodium restriction in CKD patients specifically. Recent findings Sodium intake in CKD populations is generally high, and often above population average. Recent data demonstrated that moderately lower sodium intake in CKD patients is associated with substantially better long-term outcome of renin–angiotensin–aldosterone system (RAAS)-blockade, in diabetic and nondiabetic CKD, related to better effects of RAAS-blockade on proteinuria, independent of blood pressure. This is in line with better short-term efficacy of RAAS-blockade during moderate sodium restriction in diabetic and nondiabetic CKD. This effect of sodium restriction is likely mediated by its effects on volume status. Sustainable sodium restriction can be achieved by approaches on the basis of behavioral sciences. Summary Moderate restriction of dietary sodium can substantially improve the protective effects of RAAS-blockade in CKD, by specific renal effects apparent from proteinuria reduction. The latter precludes straightforward extrapolation of data from nonrenal populations to CKD. Concerns regarding the adverse effects of a very low sodium intake should not distract from the protective effects of moderate sodium restriction. Prospective studies should assess the efficacy and sustainability of different strategies to target high sodium intake in CKD, along with measures at population level. Video abstract http://links.lww.com/CONH/A14 PMID:25222815

Catalpol Modulates Lifespan via DAF-16/FOXO and SKN-1/Nrf2 Activation in Caenorhabditis elegans

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Hyun Won Seo

2015-01-01

Full Text Available Catalpol is an effective component of rehmannia root and known to possess various pharmacological properties. The present study was aimed at investigating the potential effects of catalpol on the lifespan and stress tolerance using C. elegans model system. Herein, catalpol showed potent lifespan extension of wild-type nematode under normal culture condition. In addition, survival rate of catalpol-fed nematodes was significantly elevated compared to untreated control under heat and oxidative stress but not under hyperosmolality conditions. We also found that elevated antioxidant enzyme activities and expressions of stress resistance proteins were attributed to catalpol-mediated increased stress tolerance of nematode. We further investigated whether catalpol’s longevity effect is related to aging-related factors including reproduction, food intake, and growth. Interestingly, catalpol exposure could attenuate pharyngeal pumping rate, indicating that catalpol may induce dietary restriction of nematode. Moreover, locomotory ability of aged nematode was significantly improved by catalpol treatment, while lipofuscin levels were attenuated, suggesting that catalpol may affect age-associated changes of nematode. Our mechanistic studies revealed that mek-1, daf-2, age-1, daf-16, and skn-1 are involved in catalpol-mediated longevity. These results indicate that catalpol extends lifespan and increases stress tolerance of C. elegans via DAF-16/FOXO and SKN-1/Nrf activation dependent on insulin/IGF signaling and JNK signaling.

The effect of dietary restriction on reproduction: a meta-analytic perspective.

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Moatt, Joshua P; Nakagawa, Shinichi; Lagisz, Malgorzata; Walling, Craig A

2016-10-07

Dietary restriction (DR), a reduction in the amount of food or particular nutrients eaten, is the most consistent environmental manipulation to extend lifespan and protect against age related diseases. Current evolutionary theory explains this effect as a shift in the resolution of the trade-off between lifespan and reproduction. However, recent studies have questioned the role of reproduction in mediating the effect of DR on longevity and no study has quantitatively investigated the effect of DR on reproduction across species. Here we report a comprehensive comparative meta-analysis of the effect of DR on reproduction. In general, DR reduced reproduction across taxa, but several factors moderated this effect. The effect of DR on reproduction was greater in well-studied model species (yeast, nematode worms, fruit flies and rodents) than non-model species. This mirrors recent results for longevity and, for reproduction, seems to result from a faster rate of decline with decreasing resources in model species. Our results also suggested that not all reproductive traits are affected equally by DR. High and moderate cost reproductive traits suffered a significant reduction with DR, but low cost traits, such as ejaculate production, did not. Although the effect of DR on reproduction was stronger in females than males, this sex difference reduced to near zero when accounting for other co-factors such as the costliness of the reproductive trait. Thus, sex differences in the effect of DR on longevity may be due to a failure to expose males to as complete a range of the costs of reproduction as females. We suggest that to better understand the generality of the effect of DR, future studies should attempt to address the cause of the apparent model species bias and ensure that individuals are exposed to as many of the costs of reproduction as possible. Furthermore, our meta-analytic approach reveals a general shortage of DR studies that record reproduction, particularly in

Functional loss of two ceramide synthases elicits autophagy-dependent lifespan extension in C. elegans.

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Mai-Britt Mosbech

Full Text Available Ceramide and its metabolites constitute a diverse group of lipids, which play important roles as structural entities of biological membranes as well as regulators of cellular growth, differentiation, and development. The C. elegans genome comprises three ceramide synthase genes; hyl-1, hyl-2, and lagr-1. HYL-1 function is required for synthesis of ceramides and sphingolipids containing very long acyl-chains (≥C24, while HYL-2 is required for synthesis of ceramides and sphingolipids containing shorter acyl-chains (≤C22. Here we show that functional loss of HYL-2 decreases lifespan, while loss of HYL-1 or LAGR-1 does not affect lifespan. We show that loss of HYL-1 and LAGR-1 functions extend lifespan in an autophagy-dependent manner, as knock down of the autophagy-associated gene ATG-12 abolishes hyl-1;lagr-1 longevity. The transcription factors PHA-4/FOXA, DAF-16/FOXO, and SKN-1 are also required for the observed lifespan extension, as well as the increased number of autophagosomes in hyl-1;lagr-1 animals. Both autophagic events and the transcription factors PHA-4/FOXA, DAF-16, and SKN-1 have previously been associated with dietary restriction-induced longevity. Accordingly, we find that hyl-1;lagr-1 animals display reduced feeding, increased resistance to heat, and reduced reproduction. Collectively, our data suggest that specific sphingolipids produced by different ceramide synthases have opposing roles in determination of C. elegans lifespan. We propose that loss of HYL-1 and LAGR-1 result in dietary restriction-induced autophagy and consequently prolonged longevity.

Caloric Restriction-Induced Extension of Chronological Lifespan Requires Intact Respiration in Budding Yeast.

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Kwon, Young-Yon; Lee, Sung-Keun; Lee, Cheol-Koo

2017-04-01

Caloric restriction (CR) has been shown to extend lifespan and prevent cellular senescence in various species ranging from yeast to humans. Many effects of CR may contribute to extend lifespan. Specifically, CR prevents oxidative damage from reactive oxygen species (ROS) by enhancing mitochondrial function. In this study, we characterized 33 single electron transport chain (ETC) gene-deletion strains to identify CR-induced chronological lifespan (CLS) extension mechanisms. Interestingly, defects in 17 of these 33 ETC gene-deleted strains showed loss of both respiratory function and CR-induced CLS extension. On the contrary, the other 16 respiration-capable mutants showed increased CLS upon CR along with increased mitochondrial membrane potential (MMP) and intracellular adenosine triphosphate (ATP) levels, with decreased mitochondrial superoxide generation. We measured the same parameters in the 17 non-respiratory mutants upon CR. CR simultaneously increased MMP and mitochondrial superoxide generation without altering intracellular ATP levels. In conclusion, respiration is essential for CLS extension by CR and is important for balancing MMP, ROS, and ATP levels.

p16(INK4a suppression by glucose restriction contributes to human cellular lifespan extension through SIRT1-mediated epigenetic and genetic mechanisms.

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Yuanyuan Li

2011-02-01

Full Text Available Although caloric restriction (CR has been shown to increase lifespan in various animal models, the mechanisms underlying this phenomenon have not yet been revealed. We developed an in vitro system to mimic CR by reducing glucose concentration in cell growth medium which excludes metabolic factors and allows assessment of the effects of CR at the cellular and molecular level. We monitored cellular proliferation of normal WI-38, IMR-90 and MRC-5 human lung fibroblasts and found that glucose restriction (GR can inhibit cellular senescence and significantly extend cellular lifespan compared with cells receiving normal glucose (NG in the culture medium. Moreover, GR decreased expression of p16(INK4a (p16, a well-known senescence-related gene, in all of the tested cell lines. Over-expressed p16 resulted in early replicative senescence in glucose-restricted cells suggesting a crucial role of p16 regulation in GR-induced cellular lifespan extension. The decreased expression of p16 was partly due to GR-induced chromatin remodeling through effects on histone acetylation and methylation of the p16 promoter. GR resulted in an increased expression of SIRT1, a NAD-dependent histone deacetylase, which has positive correlation with CR-induced longevity. The elevated SIRT1 was accompanied by enhanced activation of the Akt/p70S6K1 signaling pathway in response to GR. Furthermore, knockdown of SIRT1 abolished GR-induced p16 repression as well as Akt/p70S6K1 activation implying that SIRT1 may affect p16 repression through direct deacetylation effects and indirect regulation of Akt/p70S6K1 signaling. Collectively, these results provide new insights into interactions between epigenetic and genetic mechanisms on CR-induced longevity that may contribute to anti-aging approaches and also provide a general molecular model for studying CR in vitro in mammalian systems.

A review of associations between family or shared meal frequency and dietary and weight status outcomes across the lifespan.

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Fulkerson, Jayne A; Larson, Nicole; Horning, Melissa; Neumark-Sztainer, Dianne

2014-01-01

To summarize the research literature on associations between family meal frequency and dietary outcomes as well as weight status across the lifespan. Reviewed literature of family or shared meals with dietary and weight outcomes in youth, adults, and older adults. Across the lifespan, eating with others, particularly family, is associated with healthier dietary outcomes. Among children and adolescents, these findings appear to be consistent for both boys and girls, whereas mixed findings are seen by gender for adult men and women. The findings of associations between family or shared meals and weight outcomes across the lifespan are less consistent and more complicated than those of dietary outcomes. Now is the time for the field to improve understanding of the mechanisms involved in the positive associations seen with family meal frequency, and to move forward with implementing interventions aimed at increasing the frequency of, and improving the quality of, food served at family meals, and evaluating their impact. Given the more limited findings of associations between family or shared meals and weight outcomes, capitalizing on the positive benefits of family and shared meals while addressing the types of foods served, portion sizes, and other potential mechanisms may have a significant impact on obesity prevention and reduction. Future research recommendations are provided. Copyright © 2014 Society for Nutrition Education and Behavior. Published by Elsevier Inc. All rights reserved.

Eclampsia despite strict dietary sodium restriction.

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Delemarre, F.M.C.; Steegers, E.A.P.; Berendes, J.N.

2001-01-01

The classic indication for prescribing dietary sodium restriction in pregnancy has been the prevention of eclampsia. We describe a case of intrapartum eclampsia in a 24-year-old nulliparous woman. A strongly sodium restricted diet was prescribed because of pre-eclampsia. Compliance to the diet was

Dietary sodium restriction and β2-adrenergic receptor polymorphism modulate cardiovascular function in humans

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Eisenach, John H; Schroeder, Darrell R; Pike, Tasha L; Johnson, Christopher P; Schrage, William G; Snyder, Eric M; Johnson, Bruce D; Garovic, Vesna D; Turner, Stephen T; Joyner, Michael J

2006-01-01

Dietary Na+ intake influences β2-adrenergic receptor (β2AR) responsiveness. While receiving a normal Na+ diet (150 mmol day−1), subjects homozygous for glycine at amino acid 16 (Gly16) have greater forearm β2AR-mediated vasodilatation than subjects homozygous for arginine (Arg16), an effect that is mediated by endothelial NO. We tested the hypothesis that dietary Na+ restriction eliminates genotype differences in forearm and systemic β2AR-mediated dilatation in these groups. We measured heart rate, mean arterial pressure and cardiac output (CO, acetylene breathing) responses to administration of intravenous terbutaline (TRB) before and after 5 days of low dietary Na+ intake (10 mmol day−1) in healthy Gly16 (n = 17; age, 31 ± 7 year) and Arg16 homozygotes (n = 15; age, 29 ± 8 year). After the low-Na+ diet, a catheter was placed in the brachial artery to measure forearm blood flow (FBF, plethysmography) responses to administration of isoprenaline (isoproterenol) before and after NO inhibition with NG-mono-methyl-l-arginine (l-NMMA). In the Gly16 group, the low-Na+ diet decreased baseline CO from 6.4 ± 1.4 to 5.5 ± 1.2 l min−1 (P = 0.003, paired t test), tended to decrease stroke volume from 97.0 ± 20.6 to 86.9 ± 21.7 ml (P = 0.06) and increased peripheral resistance from 1106 ± 246 to 1246 ± 222 dynes s cm−5 (P = 0.02); significant effects of the low-Na+ diet were not observed in Arg16 subjects. In a repeated measures ANOVA, the responses of all cardiovascular measures to systemic administration of TRB were not influenced by genotype or diet. Additionally, the FBF response to incremenetal doses of isoprenaline did not differ between genotype groups before or after administration of l-NMMA. We conclude that dietary Na+ restriction blunted the increased forearm NO-mediated β2AR responsiveness in Gly16 homozygotes observed in a previous study after normal dietary Na+ intake, while baseline CO decreased and peripheral resistance increased in this

Dietary restriction improves repopulation but impairs lymphoid differentiation capacity of hematopoietic stem cells in early aging

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Tang, Duozhuang; Tao, Si; Chen, Zhiyang; Koliesnik, Ievgen Oleksandrovich; Calmes, Philip Gerald; Hoerr, Verena; Han, Bing; Gebert, Nadja; Zörnig, Martin; Löffler, Bettina

2016-01-01

Dietary restriction (DR) improves health, delays tissue aging, and elongates survival in flies and worms. However, studies on laboratory mice and nonhuman primates revealed ambiguous effects of DR on lifespan despite improvements in health parameters. In this study, we analyzed consequences of adult-onset DR (24 h to 1 yr) on hematopoietic stem cell (HSC) function. DR ameliorated HSC aging phenotypes, such as the increase in number of HSCs and the skewing toward myeloid-biased HSCs during aging. Furthermore, DR increased HSC quiescence and improved the maintenance of the repopulation capacity of HSCs during aging. In contrast to these beneficial effects, DR strongly impaired HSC differentiation into lymphoid lineages and particularly inhibited the proliferation of lymphoid progenitors, resulting in decreased production of peripheral B lymphocytes and impaired immune function. The study shows that DR-dependent suppression of growth factors and interleukins mediates these divergent effects caused by DR. Supplementation of insulin-like growth factor 1 partially reverted the DR-induced quiescence of HSCs, whereas IL-6/IL-7 substitutions rescued the impairment of B lymphopoiesis exposed to DR. Together, these findings delineate positive and negative effects of long-term DR on HSC functionality involving distinct stress and growth signaling pathways. PMID:26951333

Self-Reported Dietary Restrictions and Dietary Patterns in Polish Girls: A Short Research Report (GEBaHealth Study

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Grzegorz Galinski

2016-12-01

Full Text Available Dietary restraint is a commonly reported practice observed among young females. The practice remains controversial and can be interpreted as a beneficial self-regulating behavior or the opposite, an eating disorder that may have a detrimental effect on health. The aim of this short report was to investigate if dietary restrictions are associated with dietary patterns in a representative sample of Polish girls. Analyses were carried out on data from the Girls’ Eating Behavior and Health (GEBaHealth study. The sample included 1107 girls, ranging in age from 13 to 21 years old. Restrictions regarding food quantities and selected food groups were assessed using a standardized interview. Dietary patterns were identified with Principal Component Analysis (PCA, based on dietary data collected with Food Frequency Questionnaires (FFQs. Logistic regression analysis was used to study the associations between self-reported restrictions and each dietary pattern. In the total sample, 30.5% of girls reported following some food restrictions. The most common restrictions regarded consumption of sugar and/or sweets (23.7%, high-fat foods (22.4%, and fats (21.3%. Girls who declared following any restrictions, restrictions in food quantity and restrictions in the consumption of sugar and/or sweets, high-fat foods, fats, cereals and/or bread and/or potatoes were more likely to adhere to the “fruit and vegetables” (considered pro-healthy dietary pattern (adjusted odds ratios (ORs: 1.55, 95% CI: 1.14–2.12; 1.61, 95% CI: 1.17–2.21; 1.81, 95% CI: 1.30–2.52; 1.46, 95% CI: 1.04–2.06; 1.96, 95% CI: 1.38–2.80 and 3.25, 95% CI: 1.97–5.37, respectively, and less likely to adhere to the “fast foods and sweets” (unhealthy and “traditional Polish” (rather unhealthy patterns, compared to girls who declared no restrictions. Declared restrictions in the consumption of foods high in sugar, fat, and starch were observed in girls in the “fruit and

Bicarbonate-sensitive calcification and lifespan of klotho-deficient mice.

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Leibrock, Christina B; Voelkl, Jakob; Kohlhofer, Ursula; Quintanilla-Martinez, Leticia; Kuro-O, Makoto; Lang, Florian

2016-01-01

Klotho, a protein counteracting aging, is a powerful inhibitor of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] formation and regulator of mineral metabolism. In klotho hypomorphic (kl/kl) mice, excessive 1,25(OH)2D3 formation leads to hypercalcemia, hyperphosphatemia and vascular calcification, severe growth deficits, accelerated aging and early death. Kl/kl mice further suffer from extracellular volume depletion and hypotension, leading to the stimulation of antidiuretic hormone and aldosterone release. A vitamin D-deficient diet, restriction of dietary phosphate, inhibition of mineralocorticoid receptors with spironolactone, and dietary NaCl all extend the lifespan of kl/kl mice. Kl/kl mice suffer from acidosis. The present study explored whether replacement of tap drinking water by 150 mM NaHCO3 affects the growth, tissue calcification, and lifespan of kl/kl mice. As a result, NaHCO3 administration to kl/kl mice did not reverse the growth deficit but substantially decreased tissue calcification and significantly increased the average lifespan from 78 to 127 days. NaHCO3 did not significantly affect plasma concentrations of 1,25(OH)2D3 and Ca(2+) but significantly decreased plasma phosphate concentration and plasma aldosterone concentration. The present study reveals a novel effect of bicarbonate, i.e., a favorable influence on vascular calcification and early death of klotho-deficient mice. Copyright © 2016 the American Physiological Society.

Lifespan extension without fertility reduction following dietary addition of the autophagy activator Torin1 in Drosophila melanogaster.

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Mason, Janet S; Wileman, Tom; Chapman, Tracey

2018-01-01

Autophagy is a highly conserved mechanism for cellular repair that becomes progressively down-regulated during normal ageing. Hence, manipulations that activate autophagy could increase lifespan. Previous reports show that manipulations to the autophagy pathway can result in longevity extension in yeast, flies, worms and mammals. Under standard nutrition, autophagy is inhibited by the nutrient sensing kinase Target of Rapamycin (TOR). Therefore, manipulations of TOR that increase autophagy may offer a mechanism for extending lifespan. Ideally, such manipulations should be specific and minimise off-target effects, and it is important to discover additional methods for 'clean' lifespan manipulation. Here we report an initial study into the effect of up-regulating autophagy on lifespan and fertility in Drosophila melanogaster by dietary addition of Torin1. Activation of autophagy using this selective TOR inhibitor was associated with significantly increased lifespan in both sexes. Torin1 induced a dose-dependent increase in lifespan in once-mated females. There was no evidence of a trade-off between longevity and fecundity or fertility. Torin1-fed females exhibited significantly elevated fecundity, but also elevated egg infertility, resulting in no net change in overall fertility. This supports the idea that lifespan can be extended without trade-offs in fertility and suggest that Torin1 may be a useful tool with which to pursue anti-ageing research.

Urinary prostaglandin excretion in pregnancy: the effect of dietary sodium restriction.

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Delemarre, F M; Thomas, C M; van den Berg, R J; Jongsma, H W; Steegers, E A

2000-10-01

Dietary sodium restriction results in activation of the renin-angiotensin-aldosterone-system. In the non-pregnant situation renin release in response to a low sodium diet is mediated by prostaglandins. We studied the effect of dietary sodium restriction on urinary prostaglandin metabolism in pregnancy. In a randomized, longitudinal study the excretion of urinary metabolites of prostacyclin (6-keto-PGF(1 alpha)and 2,3-dinor-6-keto-PGF(1 alpha)) and thromboxane A(2)(TxB(2)and 2,3-dinor-TxB(2)) was determined throughout pregnancy and post partum in 12 women on a low sodium diet and in 12 controls. In pregnancy the excretion of all urinary prostaglandins is increased. The 6-keto-PGF(1 alpha)/ TxB(2)-ratio as well as the 2, 3-dinor-6-keto-PGF(1 alpha)/ 2,3-dinor-TxB(2)-ratio did not significantly change in pregnancy. CONCLUISION Prostacyclin and thromboxane do not seem to play an important role in sodium balance during pregnancy. Copyright 2000 Harcourt Publishers Ltd.

Towards understanding the lifespan extension by reduced insulin signaling: bioinformatics analysis of DAF-16/FOXO direct targets in Caenorhabditis elegans.

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Li, Yan-Hui; Zhang, Gai-Gai

2016-04-12

DAF-16, the C. elegans FOXO transcription factor, is an important determinant in aging and longevity. In this work, we manually curated FOXODB http://lyh.pkmu.cn/foxodb/, a database of FOXO direct targets. It now covers 208 genes. Bioinformatics analysis on 109 DAF-16 direct targets in C. elegans found interesting results. (i) DAF-16 and transcription factor PQM-1 co-regulate some targets. (ii) Seventeen targets directly regulate lifespan. (iii) Four targets are involved in lifespan extension induced by dietary restriction. And (iv) DAF-16 direct targets might play global roles in lifespan regulation.

Effect of dietary protein restriction on renal ammonia metabolism

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Lee, Hyun-Wook; Osis, Gunars; Handlogten, Mary E.; Guo, Hui; Verlander, Jill W.

2015-01-01

Dietary protein restriction has multiple benefits in kidney disease. Because protein intake is a major determinant of endogenous acid production, it is important that net acid excretion change in parallel during protein restriction. Ammonia is the primary component of net acid excretion, and inappropriate ammonia excretion can lead to negative nitrogen balance. Accordingly, we examined ammonia excretion in response to protein restriction and then we determined the molecular mechanism of the changes observed. Wild-type C57Bl/6 mice fed a 20% protein diet and then changed to 6% protein developed an 85% reduction in ammonia excretion within 2 days, which persisted during a 10-day study. The expression of multiple proteins involved in renal ammonia metabolism was altered, including the ammonia-generating enzymes phosphate-dependent glutaminase (PDG) and phosphoenolpyruvate carboxykinase (PEPCK) and the ammonia-metabolizing enzyme glutamine synthetase. Rhbg, an ammonia transporter, increased in expression in the inner stripe of outer medullary collecting duct intercalated cell (OMCDis-IC). However, collecting duct-specific Rhbg deletion did not alter the response to protein restriction. Rhcg deletion did not alter ammonia excretion in response to dietary protein restriction. These results indicate 1) dietary protein restriction decreases renal ammonia excretion through coordinated regulation of multiple components of ammonia metabolism; 2) increased Rhbg expression in the OMCDis-IC may indicate a biological role in addition to ammonia transport; and 3) Rhcg expression is not necessary to decrease ammonia excretion during dietary protein restriction. PMID:25925252

Malate and fumarate extend lifespan in Caenorhabditis elegans.

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Clare B Edwards

Full Text Available Malate, the tricarboxylic acid (TCA cycle metabolite, increased lifespan and thermotolerance in the nematode C. elegans. Malate can be synthesized from fumarate by the enzyme fumarase and further oxidized to oxaloacetate by malate dehydrogenase with the accompanying reduction of NAD. Addition of fumarate also extended lifespan, but succinate addition did not, although all three intermediates activated nuclear translocation of the cytoprotective DAF-16/FOXO transcription factor and protected from paraquat-induced oxidative stress. The glyoxylate shunt, an anabolic pathway linked to lifespan extension in C. elegans, reversibly converts isocitrate and acetyl-CoA to succinate, malate, and CoA. The increased longevity provided by malate addition did not occur in fumarase (fum-1, glyoxylate shunt (gei-7, succinate dehydrogenase flavoprotein (sdha-2, or soluble fumarate reductase F48E8.3 RNAi knockdown worms. Therefore, to increase lifespan, malate must be first converted to fumarate, then fumarate must be reduced to succinate by soluble fumarate reductase and the mitochondrial electron transport chain complex II. Reduction of fumarate to succinate is coupled with the oxidation of FADH2 to FAD. Lifespan extension induced by malate depended upon the longevity regulators DAF-16 and SIR-2.1. Malate supplementation did not extend the lifespan of long-lived eat-2 mutant worms, a model of dietary restriction. Malate and fumarate addition increased oxygen consumption, but decreased ATP levels and mitochondrial membrane potential suggesting a mild uncoupling of oxidative phosphorylation. Malate also increased NADPH, NAD, and the NAD/NADH ratio. Fumarate reduction, glyoxylate shunt activity, and mild mitochondrial uncoupling likely contribute to the lifespan extension induced by malate and fumarate by increasing the amount of oxidized NAD and FAD cofactors.

Biology of Ageing and Role of Dietary Antioxidants

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Cheng Peng

2014-01-01

Full Text Available Interest in relationship between diet and ageing is growing. Research has shown that dietary calorie restriction and some antioxidants extend lifespan in various ageing models. On the one hand, oxygen is essential to aerobic organisms because it is a final electron acceptor in mitochondria. On the other hand, oxygen is harmful because it can continuously generate reactive oxygen species (ROS, which are believed to be the factors causing ageing of an organism. To remove these ROS in cells, aerobic organisms possess an antioxidant defense system which consists of a series of enzymes, namely, superoxide dismutase (SOD, catalase (CAT, glutathione peroxidase (GPx, and glutathione reductase (GR. In addition, dietary antioxidants including ascorbic acid, vitamin A, vitamin C, α-tocopherol, and plant flavonoids are also able to scavenge ROS in cells and therefore theoretically can extend the lifespan of organisms. In this connection, various antioxidants including tea catechins, theaflavins, apple polyphenols, black rice anthocyanins, and blueberry polyphenols have been shown to be capable of extending the lifespan of fruit flies. The purpose of this review is to brief the literature on modern biological theories of ageing and role of dietary antioxidants in ageing as well as underlying mechanisms by which antioxidants can prolong the lifespan with focus on fruit flies as an model.

Cholesterol regulates DAF-16 nuclear localization and fasting-induced longevity in C. elegans.

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Ihara, Akiko; Uno, Masaharu; Miyatake, Koichi; Honjoh, Sakiko; Nishida, Eisuke

2017-01-01

Cholesterol has attracted significant attention as a possible lifespan regulator. It has been reported that serum cholesterol levels have an impact on mortality due to age-related disorders such as cardiovascular disease. Diet is also known to be an important lifespan regulator. Dietary restriction retards the onset of age-related diseases and extends lifespan in various organisms. Although cholesterol and dietary restriction are known to be lifespan regulators, it remains to be established whether cholesterol is involved in dietary restriction-induced longevity. Here, we show that cholesterol deprivation suppresses longevity induced by intermittent fasting, which is one of the dietary restriction regimens that effectively extend lifespan. We also found that cholesterol is required for the fasting-induced upregulation of transcriptional target genes such as the insulin/IGF-1 pathway effector DAF-16 and that cholesterol deprivation suppresses the long lifespan of the insulin/IGF-1 receptor daf-2 mutant. Remarkably, we found that cholesterol plays an important role in the fasting-induced nuclear accumulation of DAF-16. Moreover, knockdown of the cholesterol-binding protein NSBP-1, which has been shown to bind to DAF-16 in a cholesterol-dependent manner and to regulate DAF-16 activity, suppresses both fasting-induced longevity and DAF-16 nuclear accumulation. Furthermore, this suppression was not additive to the cholesterol deprivation-induced suppression, which suggests that NSBP-1 mediates, at least in part, the action of cholesterol to promote fasting-induced longevity and DAF-16 nuclear accumulation. These findings identify a novel role for cholesterol in the regulation of lifespan. Copyright © 2016 Elsevier Inc. All rights reserved.

Null effect of dietary restriction on prostate carcinogenesis in the Wistar-Unilever rat.

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McCormick, David L; Johnson, William D; Haryu, Todd M; Bosland, Maarten C; Lubet, Ronald A; Steele, Vernon E

2007-01-01

Chronic dietary restriction inhibits carcinogenesis in several sites in laboratory animals. To determine the effects of dietary restriction on prostate carcinogenesis, prostate cancers were induced in male Wistar-Unilever rats by a sequential regimen of cyproterone acetate (50 mg/day; 21 days); testosterone propionate (100 mg/kg/day; 3 days); N-methyl-N-nitrosourea [MNU; 30 mg/kg; single dose]; and testosterone (subcutaneous implants of 2 pellets containing 40 mg each). Dietary restriction (0% [ad libitum control], 15%, or 30%) was initiated 2 wk post-MNU, and continued until study termination at 12 mo. Dietary restriction induced a rapid suppression of body weight gain but conferred no protection against prostate carcinogenesis. 74% of carcinogen-treated ad libitum controls developed accessory sex gland cancers, versus cancer incidences of 64% and 72% in groups restricted by 15% and 30%, respectively. Similarly, 44% of dietary controls developed cancers limited to the dorsolateral/prostate, versus incidences of 45% and 53% in groups restricted by 15% and 30%. The results of the present study do not support the hypothesis that prostate carcinogenesis can be prevented by reducing caloric intake. Reducing mean body weight by up to 25% through chronic dietary restriction has no effect on the induction of prostate cancers in the Wistar-Unilever rat model.

Reduced Insulin/Insulin-like Growth Factor-1 Signaling and Dietary Restriction Inhibit Translation but Preserve Muscle Mass in Caenorhabditis elegans

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Depuydt, Geert; Xie, Fang; Petyuk, Vladislav A.; Shanmugam, Nilesh; Smolders, Arne; Dhondt, Ineke; Brewer, Heather M.; Camp, David G.; Smith, Richard D.; Braeckman, Bart P.

2013-09-03

Reduced signaling through the C. elegans insulin/IGF1 like tyrosine kinase receptor daf2 and dietary restriction via bacterial dilution are two well-characterized lifespan-extending interventions that operate in parallel or through (partially) independent mechanisms. Using accurate mass and time tag LCMS/MS quantitative proteomics we detected that the abundance of a large number of ribosomal subunits is decreased in response to dietary restriction as well as in the daf2(e1370) insulin/IGF1 receptor mutant. In addition, general protein synthesis levels in these long-lived worms are repressed. Surprisingly, ribosomal transcript levels were not correlated to actual protein abundance, suggesting that posttranscriptional regulation determines ribosome content. Proteomics also revealed increased presence of many structural muscle cell components in long-lived worms, which appears to result from prioritized preservation of muscle cell volume in nutrient-poor conditions or low insulin-like signaling. Activation of DAF16, but not diet-restriction, stimulates mRNA expression of muscle-related genes to prevent muscle atrophy. Important daf2 specific proteome changes include overexpression of aerobic metabolism enzymes and a general activation of stress responsive and immune defense systems, while increased abundance of many protein subunits of the proteasome core complex is a DR-specific characteristic.

Every-other-day feeding extends lifespan but fails to delay many symptoms of aging in mice.

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Xie, Kan; Neff, Frauke; Markert, Astrid; Rozman, Jan; Aguilar-Pimentel, Juan Antonio; Amarie, Oana Veronica; Becker, Lore; Brommage, Robert; Garrett, Lillian; Henzel, Kristin S; Hölter, Sabine M; Janik, Dirk; Lehmann, Isabelle; Moreth, Kristin; Pearson, Brandon L; Racz, Ildiko; Rathkolb, Birgit; Ryan, Devon P; Schröder, Susanne; Treise, Irina; Bekeredjian, Raffi; Busch, Dirk H; Graw, Jochen; Ehninger, Gerhard; Klingenspor, Martin; Klopstock, Thomas; Ollert, Markus; Sandholzer, Michael; Schmidt-Weber, Carsten; Weiergräber, Marco; Wolf, Eckhard; Wurst, Wolfgang; Zimmer, Andreas; Gailus-Durner, Valerie; Fuchs, Helmut; Hrabě de Angelis, Martin; Ehninger, Dan

2017-07-24

Dietary restriction regimes extend lifespan in various animal models. Here we show that longevity in male C57BL/6J mice subjected to every-other-day feeding is associated with a delayed onset of neoplastic disease that naturally limits lifespan in these animals. We compare more than 200 phenotypes in over 20 tissues in aged animals fed with a lifelong every-other-day feeding or ad libitum access to food diet to determine whether molecular, cellular, physiological and histopathological aging features develop more slowly in every-other-day feeding mice than in controls. We also analyze the effects of every-other-day feeding on young mice on shorter-term every-other-day feeding or ad libitum to account for possible aging-independent restriction effects. Our large-scale analysis reveals overall only limited evidence for a retardation of the aging rate in every-other-day feeding mice. The data indicate that every-other-day feeding-induced longevity is sufficiently explained by delays in life-limiting neoplastic disorders and is not associated with a more general slowing of the aging process in mice.Dietary restriction can extend the life of various model organisms. Here, Xie et al. show that intermittent periods of fasting achieved through every-other-day feeding protect mice against neoplastic disease but do not broadly delay organismal aging in animals.

Cutting back on the essentials: Can manipulating intake of specific amino acids modulate health and lifespan?

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Brown-Borg, Holly M; Buffenstein, Rochelle

2017-10-01

With few exceptions, nutritional and dietary interventions generally impact upon both old-age quality of life and longevity. The life prolonging effects, commonly observed with dietary restriction reportedly are linked to alterations in protein intake and specifically limiting the dietary intake of certain essential amino acids. There is however a paucity of data methodically evaluating the various essential amino acids on health- and lifespan and the mechanisms involved. Rodent diets containing either lower methionine content, or tryptophan, than that found in commercially available chow, appear to elicit beneficial effects. It is unclear whether all of these favorable effects associated with restricted intake of methionine and tryptophan are due to their specific unique properties or if restriction of other essential amino acids, or proteins in general, may produce similar results. Considerably more work remains to be done to elucidate the mechanisms by which limiting these vital molecules may delay the onset of age-associated diseases and improve quality of life at older ages. Copyright © 2016 Elsevier B.V. All rights reserved.

The sensory system acts with a neuromedin U signaling pathway to mediate food type-dependent effects on lifespan

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Adilov, Bakhtiyor

2010-01-01

In order to survive, the animal uses its sensory system to interpret the complexity of its environment. Interestingly, a subset of sensory neurons, which function in taste or olfaction, has been found to influence the lifespan of C. elegans and Drosophila. Although the mechanisms by which these neurons affect lifespan are unknown, the nature of these neurons suggest that the sensory influence on lifespan is mediated by food-derived cues. This thesis shows that sensory neurons r...

Autophagy mediates pharmacological lifespan extension by spermidine and resveratrol.

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Morselli, Eugenia; Galluzzi, Lorenzo; Kepp, Oliver; Criollo, Alfredo; Maiuri, Maria Chiara; Tavernarakis, Nektarios; Madeo, Frank; Kroemer, Guido

2009-12-23

Although autophagy has widely been conceived as a self-destructive mechanism that causes cell death, accumulating evidence suggests that autophagy usually mediates cytoprotection, thereby avoiding the apoptotic or necrotic demise of stressed cells. Recent evidence produced by our groups demonstrates that autophagy is also involved in pharmacological manipulations that increase longevity. Exogenous supply of the polyamine spermidine can prolong the lifespan of (while inducing autophagy in) yeast, nematodes and flies. Similarly, resveratrol can trigger autophagy in cells from different organisms, extend lifespan in nematodes, and ameliorate the fitness of human cells undergoing metabolic stress. These beneficial effects are lost when essential autophagy modulators are genetically or pharmacologically inactivated, indicating that autophagy is required for the cytoprotective and/or anti-aging effects of spermidine and resveratrol. Genetic and functional studies indicate that spermidine inhibits histone acetylases, while resveratrol activates the histone deacetylase Sirtuin 1 to confer cytoprotection/longevity. Although it remains elusive whether the same histones (or perhaps other nuclear or cytoplasmic proteins) act as the downstream targets of spermidine and resveratrol, these results point to an essential role of protein hypoacetylation in autophagy control and in the regulation of longevity.

Zinc Levels Modulate Lifespan through Multiple Longevity Pathways in Caenorhabditis elegans.

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Jitendra Kumar

Full Text Available Zinc is an essential trace metal that has integral roles in numerous biological processes, including enzymatic function, protein structure, and cell signaling pathways. Both excess and deficiency of zinc can lead to detrimental effects on development and metabolism, resulting in abnormalities and disease. We altered the zinc balance within Caenorhabditis elegans to examine how changes in zinc burden affect longevity and healthspan in an invertebrate animal model. We found that increasing zinc levels in vivo with excess dietary zinc supplementation decreased the mean and maximum lifespan, whereas reducing zinc levels in vivo with a zinc-selective chelator increased the mean and maximum lifespan in C. elegans. We determined that the lifespan shortening effects of excess zinc required expression of DAF-16, HSF-1 and SKN-1 proteins, whereas the lifespan lengthening effects of the reduced zinc may be partially dependent upon this set of proteins. Furthermore, reducing zinc levels led to greater nuclear localization of DAF-16 and enhanced dauer formation compared to controls, suggesting that the lifespan effects of zinc are mediated in part by the insulin/IGF-1 pathway. Additionally, zinc status correlated with several markers of healthspan in worms, including proteostasis, locomotion and thermotolerance, with reduced zinc levels always associated with improvements in function. Taken together, these data support a role for zinc in regulating both development and lifespan in C. elegans, and that suggest that regulation of zinc homeostasis in the worm may be an example of antagonistic pleiotropy.

Zinc Levels Modulate Lifespan through Multiple Longevity Pathways in Caenorhabditis elegans

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Kumar, Jitendra; Barhydt, Tracy; Awasthi, Anjali; Lithgow, Gordon J.; Killilea, David W.; Kapahi, Pankaj

2016-01-01

Zinc is an essential trace metal that has integral roles in numerous biological processes, including enzymatic function, protein structure, and cell signaling pathways. Both excess and deficiency of zinc can lead to detrimental effects on development and metabolism, resulting in abnormalities and disease. We altered the zinc balance within Caenorhabditis elegans to examine how changes in zinc burden affect longevity and healthspan in an invertebrate animal model. We found that increasing zinc levels in vivo with excess dietary zinc supplementation decreased the mean and maximum lifespan, whereas reducing zinc levels in vivo with a zinc-selective chelator increased the mean and maximum lifespan in C. elegans. We determined that the lifespan shortening effects of excess zinc required expression of DAF-16, HSF-1 and SKN-1 proteins, whereas the lifespan lengthening effects of the reduced zinc may be partially dependent upon this set of proteins. Furthermore, reducing zinc levels led to greater nuclear localization of DAF-16 and enhanced dauer formation compared to controls, suggesting that the lifespan effects of zinc are mediated in part by the insulin/IGF-1 pathway. Additionally, zinc status correlated with several markers of healthspan in worms, including proteostasis, locomotion and thermotolerance, with reduced zinc levels always associated with improvements in function. Taken together, these data support a role for zinc in regulating both development and lifespan in C. elegans, and that suggest that regulation of zinc homeostasis in the worm may be an example of antagonistic pleiotropy. PMID:27078872

Protein and Amino Acid Restriction, Aging and Disease: from yeast to humans

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Mirzaei, Hamed; Suarez, Jorge A.; Longo, Valter D.

2014-01-01

Many of the effects of dietary restriction (DR) on longevity and health span in model organisms have been linked to reduced protein and amino acid (AA) intake and the stimulation of specific nutrient signaling pathways. Studies in yeast have shown that addition of serine, threonine, and valine in media promotes cellular sensitization and aging by activating different but connected pathways. Protein or essential AA restriction extends both lifespan and healthspan in rodent models. In humans, p...

Calorie for Calorie, Dietary Fat Restriction Results in More Body Fat Loss than Carbohydrate Restriction in People with Obesity.

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Hall, Kevin D; Bemis, Thomas; Brychta, Robert; Chen, Kong Y; Courville, Amber; Crayner, Emma J; Goodwin, Stephanie; Guo, Juen; Howard, Lilian; Knuth, Nicolas D; Miller, Bernard V; Prado, Carla M; Siervo, Mario; Skarulis, Monica C; Walter, Mary; Walter, Peter J; Yannai, Laura

2015-09-01

Dietary carbohydrate restriction has been purported to cause endocrine adaptations that promote body fat loss more than dietary fat restriction. We selectively restricted dietary carbohydrate versus fat for 6 days following a 5-day baseline diet in 19 adults with obesity confined to a metabolic ward where they exercised daily. Subjects received both isocaloric diets in random order during each of two inpatient stays. Body fat loss was calculated as the difference between daily fat intake and net fat oxidation measured while residing in a metabolic chamber. Whereas carbohydrate restriction led to sustained increases in fat oxidation and loss of 53 ± 6 g/day of body fat, fat oxidation was unchanged by fat restriction, leading to 89 ± 6 g/day of fat loss, and was significantly greater than carbohydrate restriction (p = 0.002). Mathematical model simulations agreed with these data, but predicted that the body acts to minimize body fat differences with prolonged isocaloric diets varying in carbohydrate and fat. Copyright © 2015 Elsevier Inc. All rights reserved.

Nutritional Programming of Lifespan by FOXO Inhibition on Sugar-Rich Diets

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Adam J. Dobson

2017-01-01

Full Text Available Consumption of unhealthy diets is exacerbating the burden of age-related ill health in aging populations. Such diets can program mammalian physiology to cause long-term, detrimental effects. Here, we show that, in Drosophila melanogaster, an unhealthy, high-sugar diet in early adulthood programs lifespan to curtail later-life survival despite subsequent dietary improvement. Excess dietary sugar promotes insulin-like signaling, inhibits dFOXO—the Drosophila homolog of forkhead box O (FOXO transcription factors—and represses expression of dFOXO target genes encoding epigenetic regulators. Crucially, dfoxo is required both for transcriptional changes that mark the fly’s dietary history and for nutritional programming of lifespan by excess dietary sugar, and this mechanism is conserved in Caenorhabditis elegans. Our study implicates FOXO factors, the evolutionarily conserved determinants of animal longevity, in the mechanisms of nutritional programming of animal lifespan.

Nitrogen Ion Form and Spatio-temporal Variation in Root Distribution Mediate Nitrogen Effects on Lifespan of Ectomycorrhizal Roots

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Kou, L.; McCormack, M. L.; Chen, W.; Guo, D.; Wang, H.; Li, S.; Gao, W.; Yang, H.

2017-12-01

Background and Aims Absorptive roots active in soil resource uptake are often intimately associated with mycorrhizal fungi, yet it remains unclear how nitrogen (N) loading affects lifespan of absorptive roots associating with ectomycorrhizal (ECM) fungi. Methods Through a three-year minirhizotron experiment, we investigated the responses of ECM lifespan to different rates of N addition and examined the roles of N ion form, rooting depth, seasonal root cohort, and ECM morphotype in mediating the N effects on ECM lifespan in a slash pine (Pinus elliottii) forest in subtropical China. Results High rates of NH4Cl significantly decreased foliar P concentrations and increased foliar N: P ratios, and mean ECM lifespan was negatively correlated to foliar P concentration. N additions generally increased the lifespan of most ectomycorrhizas, but the specific differences were context dependent. N rates and forms exerted significant positive effects on ECM lifespan with stronger effects occurring at high N rates and under ammonium N addition. N additions extended lifespan of ectomycorrhizas in shallower soil and born in spring and autumn, but shortened lifespan of ectomycorrhizas in deeper soil and born in summer and winter. N additions reduced lifespan of dichotomous ectomycorrhizas, but increased lifespan of coralloid ectomycorrhizas. Conclusions The increased ECM lifespan in response to N additions may primarily be driven by the persistent and aggravated P limitation to plants. Our findings highlight the importance of environmental contexts in controlling ECM lifespan and the need to consider potential differences among mycorrhizal morphotypes when studying N—lifespan relationships of absorptive roots in the context of N deposition.

Telomerase-mediated life-span extension of human primary fibroblasts by human artificial chromosome (HAC) vector

International Nuclear Information System (INIS)

Shitara, Shingo; Kakeda, Minoru; Nagata, Keiko; Hiratsuka, Masaharu; Sano, Akiko; Osawa, Kanako; Okazaki, Akiyo; Katoh, Motonobu; Kazuki, Yasuhiro; Oshimura, Mitsuo; Tomizuka, Kazuma

2008-01-01

Telomerase-mediated life-span extension enables the expansion of normal cells without malignant transformation, and thus has been thought to be useful in cell therapies. Currently, integrating vectors including the retrovirus are used for human telomerase reverse transcriptase (hTERT)-mediated expansion of normal cells; however, the use of these vectors potentially causes unexpected insertional mutagenesis and/or activation of oncogenes. Here, we established normal human fibroblast (hPF) clones retaining non-integrating human artificial chromosome (HAC) vectors harboring the hTERT expression cassette. In hTERT-HAC/hPF clones, we observed the telomerase activity and the suppression of senescent-associated SA-β-galactosidase activity. Furthermore, the hTERT-HAC/hPF clones continued growing beyond 120 days after cloning, whereas the hPF clones retaining the silent hTERT-HAC senesced within 70 days. Thus, hTERT-HAC-mediated episomal expression of hTERT allows the extension of the life-span of human primary cells, implying that gene delivery by non-integrating HAC vectors can be used to control cellular proliferative capacity of primary cultured cells

A naturalistic examination of body checking and dietary restriction in women with anorexia nervosa.

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Lavender, Jason M; Wonderlich, Stephen A; Crosby, Ross D; Engel, Scott G; Mitchell, James E; Crow, Scott; Peterson, Carol B; Le Grange, Daniel

2013-08-01

Body checking has been conceptualized as a behavioral manifestation of the core overvaluation of eating, shape, and weight concerns underlying eating disorder psychopathology. Cognitive-behavioral theories suggest that body checking behaviors may function to maintain dietary restriction. The current study examined the association between body checking frequency and dietary restriction among women with anorexia nervosa (AN) in the natural environment. Women (N = 118) with full or partial AN completed baseline clinical interviews and a two-week ecological momentary assessment protocol, during which they reported on body checking behaviors (i.e., checking whether one's thighs touch; checking joints/bones for fat) and dietary restriction (i.e., 8 waking hours without eating; consuming less than 1200 calories per day). Average daily body checking frequency was positively associated with baseline eating disorder symptoms and body mass index. Daily body checking frequency was associated with both forms of dietary restriction on the same day, as well as the following day. Results support the theorized association between body checking and overvaluation of shape and weight, and suggest that targeting such behaviors in treatment may have utility in reducing dietary restriction. Copyright © 2013 Elsevier Ltd. All rights reserved.

Prolongevity effects of a botanical with oregano and cranberry extracts in Mexican fruit flies: examining interactions of diet restriction and age

OpenAIRE

Zou, Sige; Carey, James R.; Liedo, Pablo; Ingram, Donald K.; Yu, Binbing

2011-01-01

Botanicals rich with phytochemicals have numerous health benefits. Dietary restriction (DR) extends lifespan in diverse species. We previously demonstrated that an oregano–cranberry (OC) mixture can promote longevity in the Mexican Fruit fly (Mexfly, Anastrepha ludens Loew). However, little is known about the interaction between botanicals and DR, and the age-dependent effect of botanicals on lifespan and reproduction. Here we investigated these issues by feeding Mexflies a full or DR diet su...

Expectancies related to thinness, dietary restriction, eating, and alcohol consumption in women with bulimia nervosa.

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Bruce, Kenneth; Mansour, Sandra; Steiger, Howard

2009-04-01

To investigate behavior-outcome expectancies relating to thinness, dietary restriction, eating, and alcohol consumption in women with bulimia nervosa (BN). Women with BN (N = 29), women with BN and a co-morbid lifetime alcohol use disorder (AUD; N = 18), and control women (N = 24), completed interviews and questionnaires assessing eating- and alcohol-related symptoms, as well as questionnaires measuring expectancies relating to thinness, dietary restriction, eating, and alcohol consumption. Compared with the control group, both bulimic groups reported greater positive expectancies relating to thinness, dietary restriction and eating; expectancy endorsements were also predictive of the severity of eating-related symptoms. Compared with the other groups, the bulimic group with comorbid lifetime AUD had elevated positive alcohol-related expectancies, and alcohol expectancy endorsements predicted severity of alcohol-related symptoms. Women with BN endorsed more positive expectancies relating to thinness, dietary restriction, and eating, whereas women with BN and a lifetime comorbid AUD endorsed more positive alcohol expectancies. The results are consistent with expectancy theory in that positive expectancy endorsements were associated with symptom severity in a syndrome-specific manner. Expectancies related to thinness, dietary restriction, eating, and alcohol consumption in women with BN. (c) 2008 by Wiley Periodicals, Inc.

Effects of dietary carbohydrate restriction versus low-fat diet on flow-mediated dilation.

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Volek, Jeff S; Ballard, Kevin D; Silvestre, Ricardo; Judelson, Daniel A; Quann, Erin E; Forsythe, Cassandra E; Fernandez, Maria Luz; Kraemer, William J

2009-12-01

We previously reported that a carbohydrate-restricted diet (CRD) ameliorated many of the traditional markers associated with metabolic syndrome and cardiovascular risk compared with a low-fat diet (LFD). There remains concern how CRD affects vascular function because acute meals high in fat have been shown to impair endothelial function. Here, we extend our work and address these concerns by measuring fasting and postprandial vascular function in 40 overweight men and women with moderate hypertriacylglycerolemia who were randomly assigned to consume hypocaloric diets (approximately 1500 kcal) restricted in carbohydrate (percentage of carbohydrate-fat-protein = 12:59:28) or LFD (56:24:20). Flow-mediated dilation of the brachial artery was assessed before and after ingestion of a high-fat meal (908 kcal, 84% fat) at baseline and after 12 weeks. Compared with the LFD, the CRD resulted in a greater decrease in postprandial triacylglycerol (-47% vs -15%, P = .007), insulin (-51% vs -6%, P = .009), and lymphocyte (-12% vs -1%, P = .050) responses. Postprandial fatty acids were significantly increased by the CRD compared with the LFD (P = .033). Serum interleukin-6 increased significantly over the postprandial period; and the response was augmented in the CRD (46%) compared with the LFD (-13%) group (P = .038). After 12 weeks, peak flow-mediated dilation at 3 hours increased from 5.1% to 6.5% in the CRD group and decreased from 7.9% to 5.2% in the LFD group (P = .004). These findings show that a 12-week low-carbohydrate diet improves postprandial vascular function more than a LFD in individuals with atherogenic dyslipidemia.

Ghrelin-AMPK Signaling Mediates the Neuroprotective Effects of Calorie Restriction in Parkinson's Disease

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Bayliss, Jacqueline A.; Lemus, Moyra B.; Stark, Romana; Santos, Vanessa V.; Thompson, Aiysha; Rees, Daniel J.; Galic, Sandra; Elsworth, John D.; Kemp, Bruce E.; Davies, Jeffrey S.

2016-01-01

Calorie restriction (CR) is neuroprotective in Parkinson's disease (PD) although the mechanisms are unknown. In this study we hypothesized that elevated ghrelin, a gut hormone with neuroprotective properties, during CR prevents neurodegeneration in an 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model of PD. CR attenuated the MPTP-induced loss of substantia nigra (SN) dopamine neurons and striatal dopamine turnover in ghrelin WT but not KO mice, demonstrating that ghrelin mediates CR's neuroprotective effect. CR elevated phosphorylated AMPK and ACC levels in the striatum of WT but not KO mice suggesting that AMPK is a target for ghrelin-induced neuroprotection. Indeed, exogenous ghrelin significantly increased pAMPK in the SN. Genetic deletion of AMPKβ1 and 2 subunits only in dopamine neurons prevented ghrelin-induced AMPK phosphorylation and neuroprotection. Hence, ghrelin signaling through AMPK in SN dopamine neurons mediates CR's neuroprotective effects. We consider targeting AMPK in dopamine neurons may recapitulate neuroprotective effects of CR without requiring dietary intervention. SIGNIFICANCE STATEMENT The neuroprotective mechanisms of calorie restriction (CR) in Parkinson's disease are unknown. Indeed, the difficulty to adhere to CR necessitates an alternative method to recapitulate the neuroprotective benefits of CR while bypassing dietary constraints. Here we show that CR increases plasma ghrelin, which targets substantia nigra dopamine to maintain neuronal survival. Selective deletion on AMPK beta1 and beta2 subunits only in DAT cre-expressing neurons shows that the ghrelin-induced neuroprotection requires activation of AMPK in substantia nigra dopamine neurons. We have discovered ghrelin as a key metabolic signal, and AMPK in dopamine neurons as its target, which links calorie restriction with neuroprotection in Parkinson's disease. Thus, targeting AMPK in dopamine neurons may provide novel neuroprotective benefits in Parkinson's disease. PMID

Exercise coupled with dietary restriction reduces oxidative stress in male adolescents with obesity.

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Li, Chunyan; Feng, Feihu; Xiong, Xiaoling; Li, Rui; Chen, Ning

2017-04-01

The increased oxidative stress is usually observed in obese population, but the control of body weight by calorie restriction and/or exercise training can ameliorate oxidative stress. In order to evaluate oxidative stress in response to exercise and dietary restriction in obese adolescents, a total of 20 obese volunteers were enrolled in a 4-week intervention program including exercise training and dietary restriction. Body compositions and blood samples were analysed before and after 4-week intervention, and biomarkers associated with oxidative stress were examined. After 4-week exercise training coupled with dietary restriction, physical composition parameters including body mass, body mass index (BMI), lean body mass, body fat mass and fat mass ratio had obvious reduction by 12.43%, 13.51%, 5.83%, 25.05% and 14.52%, respectively. In addition, the activities of antioxidant enzymes, such as superoxide dismutase (SOD) and glutathione peroxidase (GPx) revealed a remarkable enhancement. On the other hand, protein carbonyls (PC) exhibited an obvious reduction. Moreover, total thiols and nitrites with respect to baseline revealed a reducing trend although no significant difference was observed. Therefore, the 4-week exercise intervention coupled with dietary restriction is benefit for the loss of body weight and the mitigation of oxidative stress in obese population so that it can be a recommendable intervention prescription for the loss of body weight.

Impact of caloric and dietary restriction regimens on markers of health and longevity in humans and animals: a summary of available findings

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Kabir Mohammad M

2011-10-01

Full Text Available Abstract Considerable interest has been shown in the ability of caloric restriction (CR to improve multiple parameters of health and to extend lifespan. CR is the reduction of caloric intake - typically by 20 - 40% of ad libitum consumption - while maintaining adequate nutrient intake. Several alternatives to CR exist. CR combined with exercise (CE consists of both decreased caloric intake and increased caloric expenditure. Alternate-day fasting (ADF consists of two interchanging days; one day, subjects may consume food ad libitum (sometimes equaling twice the normal intake; on the other day, food is reduced or withheld altogether. Dietary restriction (DR - restriction of one or more components of intake (typically macronutrients with minimal to no reduction in total caloric intake - is another alternative to CR. Many religions incorporate one or more forms of food restriction. The following religious fasting periods are featured in this review: 1 Islamic Ramadan; 2 the three principal fasting periods of Greek Orthodox Christianity (Nativity, Lent, and the Assumption; and 3 the Biblical-based Daniel Fast. This review provides a summary of the current state of knowledge related to CR and DR. A specific section is provided that illustrates related work pertaining to religious forms of food restriction. Where available, studies involving both humans and animals are presented. The review includes suggestions for future research pertaining to the topics of discussion.

Impact of caloric and dietary restriction regimens on markers of health and longevity in humans and animals: a summary of available findings

Science.gov (United States)

2011-01-01

Considerable interest has been shown in the ability of caloric restriction (CR) to improve multiple parameters of health and to extend lifespan. CR is the reduction of caloric intake - typically by 20 - 40% of ad libitum consumption - while maintaining adequate nutrient intake. Several alternatives to CR exist. CR combined with exercise (CE) consists of both decreased caloric intake and increased caloric expenditure. Alternate-day fasting (ADF) consists of two interchanging days; one day, subjects may consume food ad libitum (sometimes equaling twice the normal intake); on the other day, food is reduced or withheld altogether. Dietary restriction (DR) - restriction of one or more components of intake (typically macronutrients) with minimal to no reduction in total caloric intake - is another alternative to CR. Many religions incorporate one or more forms of food restriction. The following religious fasting periods are featured in this review: 1) Islamic Ramadan; 2) the three principal fasting periods of Greek Orthodox Christianity (Nativity, Lent, and the Assumption); and 3) the Biblical-based Daniel Fast. This review provides a summary of the current state of knowledge related to CR and DR. A specific section is provided that illustrates related work pertaining to religious forms of food restriction. Where available, studies involving both humans and animals are presented. The review includes suggestions for future research pertaining to the topics of discussion. PMID:21981968

Impact of caloric and dietary restriction regimens on markers of health and longevity in humans and animals: a summary of available findings.

Science.gov (United States)

Trepanowski, John F; Canale, Robert E; Marshall, Kate E; Kabir, Mohammad M; Bloomer, Richard J

2011-10-07

Considerable interest has been shown in the ability of caloric restriction (CR) to improve multiple parameters of health and to extend lifespan. CR is the reduction of caloric intake - typically by 20 - 40% of ad libitum consumption - while maintaining adequate nutrient intake. Several alternatives to CR exist. CR combined with exercise (CE) consists of both decreased caloric intake and increased caloric expenditure. Alternate-day fasting (ADF) consists of two interchanging days; one day, subjects may consume food ad libitum (sometimes equaling twice the normal intake); on the other day, food is reduced or withheld altogether. Dietary restriction (DR) - restriction of one or more components of intake (typically macronutrients) with minimal to no reduction in total caloric intake - is another alternative to CR. Many religions incorporate one or more forms of food restriction. The following religious fasting periods are featured in this review: 1) Islamic Ramadan; 2) the three principal fasting periods of Greek Orthodox Christianity (Nativity, Lent, and the Assumption); and 3) the Biblical-based Daniel Fast. This review provides a summary of the current state of knowledge related to CR and DR. A specific section is provided that illustrates related work pertaining to religious forms of food restriction. Where available, studies involving both humans and animals are presented. The review includes suggestions for future research pertaining to the topics of discussion.

Effect of dietary restriction and hay inclusion in the diet of slow-growing broilers

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Karla P. Picoli

2014-11-01

Full Text Available The objective of this study was to evaluate the effect of dietary restriction and inclusion of alfalfa (Medicago sativa L. and Bermudagrass (Cynodon dactylon cv Coastal hays in the diets of ISA Label JA57 slow-growing male broilers on performance, gastrointestinal tract characteristics, and economic viability. A total of 272 broilers at 21 days old were distributed in a randomized experimental design with four treatments, four replicates, and 17 birds per experimental unit. The treatments consisted of ad libitum concentrated feed (control intake, feed restriction (80% of the control intake, and feed restrictions with supplementation of alfalfa hay (80% of the control intake+20% alfalfa or Bermudagrass hay (80% control intake+20% Bermuda. Dietary restriction, with and without hay inclusion, negatively affected (P<0.05 the weight gain of the birds; however, feed conversion was improved (P<0.05 for animals that underwent only restricted feeding, which also had the best economic indices. Birds subjected to dietary restriction and inclusion of hays showed changes (P<0.05 in the gastrointestinal organs and intestinal morphology.

Chronic Caloric Restriction and Exercise Improve Metabolic Conditions of Dietary-Induced Obese Mice in Autophagy Correlated Manner without Involving AMPK

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Mingxia Cui

2013-01-01

Full Text Available Aim. To investigate the role of AMPK activation and autophagy in mediating the beneficial effects of exercise and caloric restriction in obesity. Methods. Dietary-induced obesity mice were made and divided into 5 groups; one additional group of normal mice serves as control. Mice in each group received different combinations of interventions including low fat diet, caloric restriction, and exercise. Then their metabolic conditions were assessed by measuring serum glucose and insulin, serum lipids, and liver function. AMPK phosphorylation and autophagy activity were detected by western blotting. Results. Obese mice models were successfully induced by high fat diet. Caloric restriction consistently improved the metabolic conditions of the obese mice, and the effects are more prominent than the mice that received only exercise. Also, caloric restriction, exercise, and low fat diet showed a synergistic effect in the improvement of metabolic conditions. Western blotting results showed that this improvement was not related with the activation of AMPK in liver, skeletal muscle, or heart but correlates well with the autophagy activity. Conclusion. Caloric restriction has more prominent beneficial effects than exercise in dietary-induced obese mice. These effects are correlated with the autophagy activity and may be independent of AMPK activation.

Dietary restriction ameliorates haematopoietic ageing independent of telomerase, whilst lack of telomerase and short telomeres exacerbates the ageing phenotype.

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Al-Ajmi, Nouf; Saretzki, Gabriele; Miles, Colin; Spyridopoulos, Ioakim

2014-10-01

Ageing is associated with an overall decline in the functional capacity of tissues and stem cells, including haematopoietic stem and progenitor cells (HSPCs), as well as telomere dysfunction. Dietary restriction (DR) is a recognised anti-ageing intervention that extends lifespan and improves health in several organisms. To investigate the role of telomeres and telomerase in haematopoietic ageing, we compared the HSPC profile and clonogenic capacity of bone marrow cells from wild type with telomerase-deficient mice and the effect of DR on these parameters. Compared with young mice, aged wild type mice demonstrated a significant accumulation of HSPCs (1.3% vs 0.2%, P=0.002) and elevated numbers of granulocyte/macrophage colony forming units (CFU-GM, 26.4 vs 17.3, P=0.0037) consistent with myeloid "skewing" of haematopoiesis. DR was able to restrict the increase in HSPC number as well as the myeloid "skewing" in aged wild type mice. In order to analyse the influence of short telomeres on the ageing phenotype we examined mice lacking the RNA template for telomerase, TERC(-/-). Telomere shortening resulted in a similar bone marrow phenotype to that seen in aged mice, with significantly increased HSPC numbers and an increased formation of all myeloid colony types but at a younger age than wild type mice. However, an additional increase in erythroid colonies (BFU-E) was also evident. Mice lacking telomerase reverse transcriptase without shortened telomeres, TERT(-/-), also presented with augmented haematopoietic ageing which was ameliorated by DR, demonstrating that the effect of DR was not dependent on the presence of telomerase in HSPCs. We conclude that whilst shortened telomeres mimic some aspects of haematopoietic ageing, both shortened telomeres and the lack of telomerase produce specific phenotypes, some of which can be prevented by dietary restriction. Copyright © 2014 Elsevier Inc. All rights reserved.

DAF-2/insulin-like signaling in C. elegans modifies effects of dietary restriction and nutrient stress on aging, stress and growth.

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Wendy B Iser

2007-11-01

Full Text Available Dietary restriction (DR and reduced insulin/IGF-I-like signaling (IIS are two regimens that promote longevity in a variety of organisms. Genetic analysis in C. elegans nematodes has shown that DR and IIS couple to distinct cellular signaling pathways. However, it is not known whether these pathways ultimately converge on overlapping or distinct targets to extend lifespan.We investigated this question by examining additional effects of DR in wildtype animals and in daf-2 mutants with either moderate or severe IIS deficits. Surprisingly, DR and IIS had opposing effects on these physiological processes. First, DR induced a stress-related change in intestinal vesicle trafficking, termed the FIRE response, which was suppressed in daf-2 mutants. Second, DR did not strongly affect expression of a daf-2- and stress-responsive transcriptional reporter. Finally, DR-related growth impairment was suppressed in daf-2 mutants.These findings reveal that an important biological function of DAF-2/IIS is to enhance growth and survival under nutrient-limited conditions. However, we also discovered that levels of DAF-2 pathway activity modified the effects of DR on longevity. Thus, while DR and IIS clearly affect lifespan through independent targets, there may also be some prolongevity targets that are convergently regulated by these pathways.

DAF-2/insulin-like signaling in C. elegans modifies effects of dietary restriction and nutrient stress on aging, stress and growth.

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Iser, Wendy B; Wolkow, Catherine A

2007-11-28

Dietary restriction (DR) and reduced insulin/IGF-I-like signaling (IIS) are two regimens that promote longevity in a variety of organisms. Genetic analysis in C. elegans nematodes has shown that DR and IIS couple to distinct cellular signaling pathways. However, it is not known whether these pathways ultimately converge on overlapping or distinct targets to extend lifespan. We investigated this question by examining additional effects of DR in wildtype animals and in daf-2 mutants with either moderate or severe IIS deficits. Surprisingly, DR and IIS had opposing effects on these physiological processes. First, DR induced a stress-related change in intestinal vesicle trafficking, termed the FIRE response, which was suppressed in daf-2 mutants. Second, DR did not strongly affect expression of a daf-2- and stress-responsive transcriptional reporter. Finally, DR-related growth impairment was suppressed in daf-2 mutants. These findings reveal that an important biological function of DAF-2/IIS is to enhance growth and survival under nutrient-limited conditions. However, we also discovered that levels of DAF-2 pathway activity modified the effects of DR on longevity. Thus, while DR and IIS clearly affect lifespan through independent targets, there may also be some prolongevity targets that are convergently regulated by these pathways.

Mannan-Binding Lectin Is Involved in the Protection against Renal Ischemia/Reperfusion Injury by Dietary Restriction.

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Shushimita Shushimita

Full Text Available Preoperative fasting and dietary restriction offer robust protection against renal ischemia/reperfusion injury (I/RI in mice. We recently showed that Mannan-binding lectin (MBL, the initiator of the lectin pathway of complement activation, plays a pivotal role in renal I/RI. Based on these findings, we investigated the effect of short-term DR (30% reduction of total food intake or three days of water only fasting on MBL in 10-12 weeks old male C57/Bl6 mice. Both dietary regimens significantly reduce the circulating levels of MBL as well as its mRNA expression in liver, the sole production site of MBL. Reconstitution of MBL abolished the protection afforded by dietary restriction, whereas in the fasting group the protection persisted. These data show that modulation of MBL is involved in the protection against renal I/RI induced by dietary restriction, and suggest that the mechanisms of protection induced by dietary restriction and fasting may be different.

Benefits of dietary sodium restriction in the management of chronic kidney disease

NARCIS (Netherlands)

Krikken, Jan A.; Laverman, Gozewijn D.; Navis, Gerjan

2009-01-01

Purpose of review To evaluate the role of restricting dietary sodium intake in chronic kidney disease (CKD) and its complications. Recent findings A consistent line of evidence shows that high dietary sodium intake is a determinant of therapy resistance to blockade of the

The clinical efficacy of dietary fat restriction in treatment of dogs with intestinal lymphangiectasia.

Science.gov (United States)

Okanishi, H; Yoshioka, R; Kagawa, Y; Watari, T

2014-01-01

Intestinal lymphangiectasia (IL), a type of protein-losing enteropathy (PLE), is a dilatation of lymphatic vessels within the gastrointestinal tract. Dietary fat restriction previously has been proposed as an effective treatment for dogs with PLE, but limited objective clinical data are available on the efficacy of this treatment. To investigate the clinical efficacy of dietary fat restriction in dogs with IL that were unresponsive to prednisolone treatment or showed relapse of clinical signs and hypoalbuminemia when the prednisolone dosage was decreased. Twenty-four dogs with IL. Retrospective study. Body weight, clinical activity score, and hematologic and biochemical variables were compared before and 1 and 2 months after treatment. Furthermore, the data were compared between the group fed only an ultra low-fat (ULF) diet and the group fed ULF and a low-fat (LF) diet. Nineteen of 24 (79%) dogs responded satisfactorily to dietary fat restriction, and the prednisolone dosage could be decreased. Clinical activity score was significantly decreased after dietary treatment compared with before treatment. In addition, albumin (ALB), total protein (TP), and blood urea nitrogen (BUN) concentration were significantly increased after dietary fat restriction. At 2 months posttreatment, the ALB concentrations in the ULF group were significantly higher than that of the ULF + LF group. Dietary fat restriction appears to be an effective treatment in dogs with IL that are unresponsive to prednisolone treatment or that have recurrent clinical signs and hypoalbuminemia when the dosage of prednisolone is decreased. © 2014 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of American College of Veterinary Internal Medicine.

A novel dietary restriction method for group-housed rats: weight gain and clinical chemistry characterization.

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Kasanen, I H E; Inhilä, K J; Nevalainen, J I; Väisänen, S B; Mertanen, A M O; Mering, S M; Nevalainen, T O

2009-04-01

Laboratory rodents are usually fed ad libitum. Moderate dietary restriction decreases mortality and morbidity compared with ad libitum feeding. There are, however, problems in achieving dietary restriction. Traditional methods of restricted feeding may interfere with the diurnal rhythms of the animals and are not compatible with group-housing of rodents. We have invented a novel method, the diet board, for restricting the feed intake of laboratory rats. The use of the diet board moderately decreased weight gain of rats when compared with ad libitum-fed animals. The diet board retarded skeletal growth only minimally, whereas major differences were found in body fat depositions. Serum free fatty acid, triglyceride and cholesterol values were lower in diet-restricted rats, while the opposite was true for serum creatine kinase. There were no differences in total protein, albumin or alanine aminotransferase. Moreover, differences in interindividual variances in parameters were not detected between the groups; hence this study could not combine the diet board with reduction potential. The diet board provides mild to moderate dietary restriction for group-housed rats and is unlikely to interfere with the diurnal eating rhythm. The diet board can also be seen as a cage furniture item, dividing the open cage space and increasing the structural complexity of the environment. In conclusion, the diet board appears to possess refinement potential when compared with traditional methods of dietary restriction.

Physiogenomic analysis of weight loss induced by dietary carbohydrate restriction

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Wood Richard J

2006-05-01

Full Text Available Abstract Background Diets that restrict carbohydrate (CHO have proven to be a successful dietary treatment of obesity for many people, but the degree of weight loss varies across individuals. The extent to which genetic factors associate with the magnitude of weight loss induced by CHO restriction is unknown. We examined associations among polymorphisms in candidate genes and weight loss in order to understand the physiological factors influencing body weight responses to CHO restriction. Methods We screened for genetic associations with weight loss in 86 healthy adults who were instructed to restrict CHO to a level that induced a small level of ketosis (CHO ~10% of total energy. A total of 27 single nucleotide polymorphisms (SNPs were selected from 15 candidate genes involved in fat digestion/metabolism, intracellular glucose metabolism, lipoprotein remodeling, and appetite regulation. Multiple linear regression was used to rank the SNPs according to probability of association, and the most significant associations were analyzed in greater detail. Results Mean weight loss was 6.4 kg. SNPs in the gastric lipase (LIPF, hepatic glycogen synthase (GYS2, cholesteryl ester transfer protein (CETP and galanin (GAL genes were significantly associated with weight loss. Conclusion A strong association between weight loss induced by dietary CHO restriction and variability in genes regulating fat digestion, hepatic glucose metabolism, intravascular lipoprotein remodeling, and appetite were detected. These discoveries could provide clues to important physiologic adaptations underlying the body mass response to CHO restriction.

Differential control of ageing and lifespan by isoforms and splice variants across the mTOR network.

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Razquin Navas, Patricia; Thedieck, Kathrin

2017-07-15

Ageing can be defined as the gradual deterioration of physiological functions, increasing the incidence of age-related disorders and the probability of death. Therefore, the term ageing not only reflects the lifespan of an organism but also refers to progressive functional impairment and disease. The nutrient-sensing kinase mTOR (mammalian target of rapamycin) is a major determinant of ageing. mTOR promotes cell growth and controls central metabolic pathways including protein biosynthesis, autophagy and glucose and lipid homoeostasis. The concept that mTOR has a crucial role in ageing is supported by numerous reports on the lifespan-prolonging effects of the mTOR inhibitor rapamycin in invertebrate and vertebrate model organisms. Dietary restriction increases lifespan and delays ageing phenotypes as well and mTOR has been assigned a major role in this process. This may suggest a causal relationship between the lifespan of an organism and its metabolic phenotype. More than 25 years after mTOR's discovery, a wealth of metabolic and ageing-related effects have been reported. In this review, we cover the current view on the contribution of the different elements of the mTOR signalling network to lifespan and age-related metabolic impairment. We specifically focus on distinct roles of isoforms and splice variants across the mTOR network. The comprehensive analysis of mouse knockout studies targeting these variants does not support a tight correlation between lifespan prolongation and improved metabolic phenotypes and questions the strict causal relationship between them. © 2017 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

The reno-protective effects of dietary caloric restriction against ...

African Journals Online (AJOL)

Studies have shown that dietary caloric restriction (CR) without malnutrition can increase longevity. This study aims to evaluate the protective effects of CR on oxidative stress, lipid peroxidation and inflammatory cytokines in the kidney of streptozotocin-induced diabetic rats. Forty 12-week old male Wistar rats, weighing ...

Sirtuins as Mediator of the Anti-Ageing Effects of Calorie Restriction in Skeletal and Cardiac Muscle

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Alberto Zullo

2018-03-01

Full Text Available Fighting diseases and controlling the signs of ageing are the major goals of biomedicine. Sirtuins, enzymes with mainly deacetylating activity, could be pivotal targets of novel preventive and therapeutic strategies to reach such aims. Scientific proofs are accumulating in experimental models, but, to a minor extent, also in humans, that the ancient practice of calorie restriction could prove an effective way to prevent several degenerative diseases and to postpone the detrimental signs of ageing. In the present review, we summarize the evidence about the central role of sirtuins in mediating the beneficial effects of calorie restriction in skeletal and cardiac muscle since these tissues are greatly damaged by diseases and advancing years. Moreover, we entertain the possibility that the identification of sirtuin activators that mimic calorie restriction could provide the benefits without the inconvenience of this dietary style.

COCOA (Theobroma cacao) Polyphenol-Rich Extract Increases the Chronological Lifespan of Saccharomyces cerevisiae.

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Baiges, I; Arola, L

2016-01-01

BACKGROUND: Saccharomyces cerevisiae is a model organism with conserved aging pathways. Yeast chronological lifespan experiments mimic the processes involved in human non-dividing tissues, such as the nervous system or skeletal muscle, and can speed up the search for biomolecules with potential anti-aging effects before proceeding to animal studies. OBJECTIVE: To test the effectiveness of a cocoa polyphenol-rich extract (CPE) in expanding the S. cerevisiae chronological lifespan in two conditions: in the stationary phase reached after glucose depletion and under severe caloric restriction. MEASUREMENTS: Using a high-throughput method, wild-type S. cerevisiae and its mitochondrial manganese-dependent superoxide dismutase null mutant (sod2Δ) were cultured in synthetic complete dextrose medium. After 2 days, 0, 5 and 20 mg/ml of CPE were added, and viability was measured throughout the stationary phase. The effects of the major components of CPE were also evaluated. To determine yeast lifespan under severe caloric restriction conditions, cultures were washed with water 24 h after the addition of 0 and 20 mg/ml of CPE, and viability was followed over time. RESULTS : CPE increased the chronological lifespan of S. cerevisiae during the stationary phase in a dose-dependent manner. A similar increase was also observed in (sod2Δ). None of the major CPE components (theobromine, caffeine, maltodextrin, (-)-epicatechin, (+)-catechin and procyanidin B2) was able to increase the yeast lifespan. CPE further increased the yeast lifespan under severe caloric restriction. CONCLUSION: CPE increases the chronological lifespan of S. cerevisiae through a SOD2-independent mechanism. The extract also extends yeast lifespan under severe caloric restriction conditions. The high-throughput assay used makes it possible to simply and rapidly test the efficacy of a large number of compounds on yeast aging, requiring only small amounts, and is thus a convenient screening assay to accelerate

CONCENTRATION-DEPENDENT LINKAGE OF DIETARY METHIONINE RESTRICTION TO THE COMPONENTS OF ITS METABOLIC PHENOTYPE

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Forney, Laura A.; Wanders, Desiree; Stone, Kirsten P.; Pierse, Alicia; Gettys, Thomas W.

2017-01-01

Objective Restricting dietary methionine to 0.17% produces a series of physiological responses through coordinated transcriptional effects in liver and adipose tissue. The goal of the present work was to determine the threshold concentrations above and below 0.17% at which the beneficial responses to 0.17% dietary methionine are preserved. Methods Diets were formulated to restrict methionine to different degrees, followed by evaluation of the transcriptional and physiological responses to the...

Effect of Intermittent Energy Restriction on Flow Mediated Dilatation, a Measure of Endothelial Function: A Short Report.

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Headland, Michelle L; Clifton, Peter M; Keogh, Jennifer B

2018-06-04

Intermittent energy restriction is a popular alternative to daily energy restriction for weight loss; however, it is unknown if endothelial function, a risk factor for cardiovascular disease, is altered by periods of severe energy restriction. The objective of the study was to determine the impact of two consecutive very low energy intake days, which is the core component of the 5:2 intermittent energy restriction diet strategy, on endothelial function compared to consecutive ad libitum eating days. The secondary objective was to explore the effects of these dietary conditions on fasting glucose concentrations. This was a 4-week randomized, single-blinded, crossover study of 35 participants. Participants consumed a very low energy diet (500 calories for women, 600 calories for men) on two consecutive days per week and 5 days of habitual eating. In weeks 3 and 4 of the trial, participants had measurements of flow mediated dilatation (FMD) and blood samples taken following either 2 habitual eating days or 2 energy restricted days in a randomized order. FMD values were not different after the two eating states (8.6% vs. 8.3%, p = 0.7). All other outcome variables were unchanged. Endothelial function, as measured by flow mediated dilatation, was not altered by two consecutive very low energy intake days. Further investigations assessing the impact in specific population groups as well as different testing conditions would be beneficial.

Acidic Food pH Increases Palatability and Consumption and Extends Drosophila Lifespan.

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Deshpande, Sonali A; Yamada, Ryuichi; Mak, Christine M; Hunter, Brooke; Soto Obando, Alina; Hoxha, Sany; Ja, William W

2015-12-01

Despite the prevalent use of Drosophila as a model in studies of nutrition, the effects of fundamental food properties, such as pH, on animal health and behavior are not well known. We examined the effect of food pH on adult Drosophila lifespan, feeding behavior, and microbiota composition and tested the hypothesis that pH-mediated changes in palatability and total consumption are required for modulating longevity. We measured the effect of buffered food (pH 5, 7, or 9) on male gustatory responses (proboscis extension), total food intake, and male and female lifespan. The effect of food pH on germfree male lifespan was also assessed. Changes in fly-associated microbial composition as a result of food pH were determined by 16S ribosomal RNA gene sequencing. Male gustatory responses, total consumption, and male and female longevity were additionally measured in the taste-defective Pox neuro (Poxn) mutant and its transgenic rescue control. An acidic diet increased Drosophila gustatory responses (40-230%) and food intake (5-50%) and extended survival (10-160% longer median lifespan) compared with flies on either neutral or alkaline pH food. Alkaline food pH shifted the composition of fly-associated bacteria and resulted in greater lifespan extension (260% longer median survival) after microbes were eliminated compared with flies on an acidic (50%) or neutral (130%) diet. However, germfree flies lived longer on an acidic diet (5-20% longer median lifespan) compared with those on either neutral or alkaline pH food. Gustatory responses, total consumption, and longevity were unaffected by food pH in Poxn mutant flies. Food pH can directly influence palatability and feeding behavior and affect parameters such as microbial growth to ultimately affect Drosophila lifespan. Fundamental food properties altered by dietary or drug interventions may therefore contribute to changes in animal physiology, metabolism, and survival. © 2015 American Society for Nutrition.

The effects of age and dietary restriction on the tissue-specific metabolome of Drosophila.

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Laye, Matthew J; Tran, ViLinh; Jones, Dean P; Kapahi, Pankaj; Promislow, Daniel E L

2015-10-01

Dietary restriction (DR) is a robust intervention that extends lifespan and slows the onset of age-related diseases in diverse organisms. While significant progress has been made in attempts to uncover the genetic mechanisms of DR, there are few studies on the effects of DR on the metabolome. In recent years, metabolomic profiling has emerged as a powerful technology to understand the molecular causes and consequences of natural aging and disease-associated phenotypes. Here, we use high-resolution mass spectroscopy and novel computational approaches to examine changes in the metabolome from the head, thorax, abdomen, and whole body at multiple ages in Drosophila fed either a nutrient-rich ad libitum (AL) or nutrient-restricted (DR) diet. Multivariate analysis clearly separates the metabolome by diet in different tissues and different ages. DR significantly altered the metabolome and, in particular, slowed age-related changes in the metabolome. Interestingly, we observed interacting metabolites whose correlation coefficients, but not mean levels, differed significantly between AL and DR. The number and magnitude of positively correlated metabolites was greater under a DR diet. Furthermore, there was a decrease in positive metabolite correlations as flies aged on an AL diet. Conversely, DR enhanced these correlations with age. Metabolic set enrichment analysis identified several known (e.g., amino acid and NAD metabolism) and novel metabolic pathways that may affect how DR effects aging. Our results suggest that network structure of metabolites is altered upon DR and may play an important role in preventing the decline of homeostasis with age. © 2015 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

The MDT-15 subunit of mediator interacts with dietary restriction to modulate longevity and fluoranthene toxicity in Caenorhabditis elegans.

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Jennifer Schleit

Full Text Available Dietary restriction (DR, the limitation of calorie intake while maintaining proper nutrition, has been found to extend life span and delay the onset of age-associated disease in a wide range of species. Previous studies have suggested that DR can reduce the lethality of environmental toxins. To further examine the role of DR in toxin response, we measured life spans of the nematode Caenorhabditis elegans treated with the mutagenic polyaromatic hydrocarbon, fluoranthene (FLA. FLA is a direct byproduct of combustion, and is one of U.S. Environmental Protection Agency's sixteen priority environmental toxins. Treatment with 5 µg/ml FLA shortened the life spans of ad libitum fed nematodes, and DR resulted in increased sensitivity to FLA. To determine the role of detoxifying enzymes in the toxicity of FLA, we tested nematodes with mutations in the gene encoding the MDT-15 subunit of mediator, a transcriptional coactivator that regulates genes involved in fatty acid metabolism and detoxification. Mutation of mdt-15 increased the life span of FLA treated animals compared to wild-type animals with no difference observed between DR and ad libitum fed mdt-15 animals. We also examined mutants with altered insulin-IGF-1-like signaling (IIS, which is known to modulate life span and stress resistance in C. elegans independently of DR. Mutation of the genes coding for the insulin-like receptor DAF-2 or the FOXO-family transcription factor DAF16 did not alter the animals' susceptibility to FLA compared to wild type. Taken together, our results suggest that certain compounds have increased toxicity when combined with a DR regimen through increased metabolic activation. This increased metabolic activation appears to be mediated through the MDT-15 transcription factor and is independent of the IIS pathway.

Effects of fluctuating temperature and food availability on reproduction and lifespan.

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Schwartz, Tonia S; Pearson, Phillip; Dawson, John; Allison, David B; Gohlke, Julia M

2016-12-15

Experimental studies on energetics and aging often remove two major factors that in part regulate the energy budget in a normal healthy individual: reproduction and fluctuating environmental conditions that challenge homeostasis. Here we use the cyclical parthenogenetic Daphnia pulex to evaluate the role of a fluctuating thermal environment on both reproduction and lifespan across six food concentrations. We test the hypotheses that (1) caloric restriction extends lifespan; (2) maximal reproduction will come with a cost of shortened lifespan; and (3) at a given food concentration, relative to a metabolically equivalent constant temperature environment a diel fluctuating thermal environment will alter the allocation of energy to reproduction and lifespan to maintain homeostasis. We did not identify a level of food concentration that extended lifespan in response to caloric restriction, and we found no cost of reproduction in terms of lifespan. Rather, the individuals at the highest food levels generally had the highest reproductive output and the longest lifespans, the individuals at the intermediate food level decreased reproduction and maintained lifespan, and the individuals at the three lower food concentrations had a decrease in reproduction and lifespan as would be predicted with increasing levels of starvation. Fluctuating temperature had no effect on lifespan at any food concentration, but delayed time to reproductive maturity and decreased early reproductive output at all food concentrations. This suggests that a fluctuating temperature regimen activates molecular pathways that alter energy allocation. The costs of fluctuating temperature on reproduction were not consistent across the lifespan. Statistical interactions for age of peak reproduction and lifetime fecundity suggest that senescence of the reproductive system may vary between temperature regimens at the different food concentrations. Copyright © 2016 Elsevier Inc. All rights reserved.

Transcriptome analysis of a long-lived natural Drosophila variant: a prominent role of stress- and reproduction-genes in lifespan extension

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Doroszuk Agnieszka

2012-05-01

Full Text Available Abstract Background While studying long-lived mutants has advanced our understanding of the processes involved in ageing, the mechanisms underlying natural variation in lifespan and ageing rate remain largely unknown. Here, we characterise genome-wide expression patterns of a long-lived, natural variant of Drosophila melanogaster resulting from selection for starvation resistance (SR and compare it with normal-lived control flies (C. We do this at two time points representing middle age (90% survival and old age (10% survival respectively, in three adult diets (malnutrition, optimal food, and overfeeding. Results We found profound differences between Drosophila lines in their age-related expression. Most of the age-associated changes in normal-lived flies were abrogated in long-lived Drosophila. The stress-related genes, including those involved in proteolysis and cytochrome P450, were generally higher expressed in SR flies and showed a smaller increase in expression with age compared to C flies. The genes involved in reproduction showed a lower expression in middle-aged SR than in C flies and, unlike C flies, a lack of their downregulation with age. Further, we found that malnutrition strongly affected age-associated transcript patterns overriding the differences between the lines. However, under less stressful dietary conditions, line and diet affected age-dependent expression similarly. Finally, we present lists of candidate markers of ageing and lifespan extension. Conclusions Our study unveils transcriptional changes associated with lifespan extension in SR Drosophila. The results suggest that natural genetic variation for SR and lifespan can operate through similar transcriptional mechanisms as those of dietary restriction and life-extending mutations.

Effect of Intermittent Energy Restriction on Flow Mediated Dilatation, a Measure of Endothelial Function: A Short Report

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Michelle L. Headland

2018-06-01

Full Text Available Intermittent energy restriction is a popular alternative to daily energy restriction for weight loss; however, it is unknown if endothelial function, a risk factor for cardiovascular disease, is altered by periods of severe energy restriction. The objective of the study was to determine the impact of two consecutive very low energy intake days, which is the core component of the 5:2 intermittent energy restriction diet strategy, on endothelial function compared to consecutive ad libitum eating days. The secondary objective was to explore the effects of these dietary conditions on fasting glucose concentrations. This was a 4-week randomized, single-blinded, crossover study of 35 participants. Participants consumed a very low energy diet (500 calories for women, 600 calories for men on two consecutive days per week and 5 days of habitual eating. In weeks 3 and 4 of the trial, participants had measurements of flow mediated dilatation (FMD and blood samples taken following either 2 habitual eating days or 2 energy restricted days in a randomized order. FMD values were not different after the two eating states (8.6% vs. 8.3%, p = 0.7. All other outcome variables were unchanged. Endothelial function, as measured by flow mediated dilatation, was not altered by two consecutive very low energy intake days. Further investigations assessing the impact in specific population groups as well as different testing conditions would be beneficial.

Dietary salt restriction improves cardiac and adipose tissue pathology independently of obesity in a rat model of metabolic syndrome.

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Hattori, Takuya; Murase, Tamayo; Takatsu, Miwa; Nagasawa, Kai; Matsuura, Natsumi; Watanabe, Shogo; Murohara, Toyoaki; Nagata, Kohzo

2014-12-02

Metabolic syndrome (MetS) enhances salt sensitivity of blood pressure and is an important risk factor for cardiovascular disease. The effects of dietary salt restriction on cardiac pathology associated with metabolic syndrome remain unclear. We investigated whether dietary salt restriction might ameliorate cardiac injury in DahlS.Z-Lepr(fa)/Lepr(fa) (DS/obese) rats, which are derived from a cross between Dahl salt-sensitive and Zucker rats and represent a model of metabolic syndrome. DS/obese rats were fed a normal-salt (0.36% NaCl in chow) or low-salt (0.0466% NaCl in chow) diet from 9 weeks of age and were compared with similarly treated homozygous lean littermates (DahlS.Z-Lepr(+)/Lepr(+), or DS/lean rats). DS/obese rats fed the normal-salt diet progressively developed hypertension and showed left ventricular hypertrophy, fibrosis, and diastolic dysfunction at 15 weeks. Dietary salt restriction attenuated all of these changes in DS/obese rats. The levels of cardiac oxidative stress and inflammation and the expression of cardiac renin-angiotensin-aldosterone system genes were increased in DS/obese rats fed the normal-salt diet, and dietary salt restriction downregulated these parameters in both DS/obese and DS/lean rats. In addition, dietary salt restriction attenuated the increase in visceral adipose tissue inflammation and the decrease in insulin signaling apparent in DS/obese rats without reducing body weight or visceral adipocyte size. Dietary salt restriction did not alter fasting serum glucose levels but it markedly decreased the fasting serum insulin concentration in DS/obese rats. Dietary salt restriction not only prevents hypertension and cardiac injury but also ameliorates insulin resistance, without reducing obesity, in this model of metabolic syndrome. © 2014 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Effect of dietary restriction and subsequent re-alimentation on the transcriptional profile of bovine jejunal epithelium.

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Keogh, Kate; Waters, Sinead M; Cormican, Paul; Kelly, Alan K; Kenny, David A

2018-01-01

Compensatory growth (CG), an accelerated growth phenomenon which occurs following a period of dietary restriction is utilised worldwide in animal production systems as a management practise to lower feed costs. The objective of this study was to evaluate the contribution of jejunal epithelial to CG in cattle through transcriptional profiling following a period of dietary restriction as well as subsequent re-alimentation induced CG. Sixty Holstein Friesian bulls were separated into two groups; RES and ADLIB, with 30 animals in each. RES animals were offered a restricted diet for 125 days (Period 1) followed by ad libitum feeding for 55 days (Period 2). ADLIB animals had ad libitum access to feed across both periods 1 and 2. At the end of each period, 15 animals from each treatment group were slaughtered, jejunal epithelium collected and RNAseq analysis performed. Animals that were previously diet restricted underwent CG, gaining 1.8 times the rate of their non-restricted counterparts. Twenty-four genes were differentially expressed in RES compared to ADLIB animals at the end of Period 1, with only one gene, GSTA1, differentially expressed between the two groups at the end of Period 2. When analysed within treatment (RES, Period 2 v Period 1), 31 genes were differentially expressed between diet restricted and animals undergoing CG. Dietary restriction and subsequent re-alimentation were associated with altered expression of genes involved in digestion and metabolism as well as those involved in cellular division and growth. Compensatory growth was also associated with greater expression of genes involved in cellular protection and detoxification in jejunal epithelium. This study highlights some of the molecular mechanisms regulating the response to dietary restriction and subsequent re-alimentation induced CG in cattle; however the gene expression results suggest that most of the CG in jejunal epithelium had occurred by day 55 of re-alimentation.

Evaluation of a Theory-Based Intervention Aimed at Reducing Intention to Use Restrictive Dietary Behaviors Among Adolescent Female Athletes.

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Laramée, Catherine; Drapeau, Vicky; Valois, Pierre; Goulet, Claude; Jacob, Raphaëlle; Provencher, Véronique; Lamarche, Benoît

2017-06-01

To evaluate the effectiveness of a theory-based intervention to reduce the intention to use restrictive dietary behaviors for losing weight among adolescent female athletes involved in aesthetic sports. Cluster-randomized controlled trial. Aesthetic sport teams of adolescent female athletes aged 12-17 years. Two teams (n = 37 athletes) in the intervention group and 3 teams (n = 33) in the comparison group. The 2 groups received nutrition education during 3 weekly 60-minute sessions. The intervention group was further exposed to a theory-based intervention targeting the specific determinant of intention to use restrictive dietary behaviors for losing weight, namely attitude. Difference over time between groups in intention to use restrictive dietary behaviors for losing weight and in nutrition knowledge. Mixed models for repeated measures. The theory-based intervention contributed to maintaining a low intention of using restrictive dietary behaviors for losing weight over time in the intervention group compared with the comparison group (P theory-based behavior change intervention may help maintain a low intention of using restrictive dietary behaviors for losing weight among female high school athletes involved in aesthetic sports. Copyright © 2017. Published by Elsevier Inc.

Distinct patterns of IFITM-mediated restriction of filoviruses, SARS coronavirus, and influenza A virus.

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I-Chueh Huang

2011-01-01

Full Text Available Interferon-inducible transmembrane proteins 1, 2, and 3 (IFITM1, 2, and 3 are recently identified viral restriction factors that inhibit infection mediated by the influenza A virus (IAV hemagglutinin (HA protein. Here we show that IFITM proteins restricted infection mediated by the entry glycoproteins (GP(1,2 of Marburg and Ebola filoviruses (MARV, EBOV. Consistent with these observations, interferon-β specifically restricted filovirus and IAV entry processes. IFITM proteins also inhibited replication of infectious MARV and EBOV. We observed distinct patterns of IFITM-mediated restriction: compared with IAV, the entry processes of MARV and EBOV were less restricted by IFITM3, but more restricted by IFITM1. Moreover, murine Ifitm5 and 6 did not restrict IAV, but efficiently inhibited filovirus entry. We further demonstrate that replication of infectious SARS coronavirus (SARS-CoV and entry mediated by the SARS-CoV spike (S protein are restricted by IFITM proteins. The profile of IFITM-mediated restriction of SARS-CoV was more similar to that of filoviruses than to IAV. Trypsin treatment of receptor-associated SARS-CoV pseudovirions, which bypasses their dependence on lysosomal cathepsin L, also bypassed IFITM-mediated restriction. However, IFITM proteins did not reduce cellular cathepsin activity or limit access of virions to acidic intracellular compartments. Our data indicate that IFITM-mediated restriction is localized to a late stage in the endocytic pathway. They further show that IFITM proteins differentially restrict the entry of a broad range of enveloped viruses, and modulate cellular tropism independently of viral receptor expression.

Dietary management of chronic kidney disease: protein restriction and beyond.

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Goraya, Nimrit; Wesson, Donald E

2012-11-01

More kidney protective strategies are needed to reduce the burden of complete kidney failure from chronic kidney disease (CKD). Clinicians sometimes use protein restriction as kidney protection despite its demonstrated lack of effectiveness in the only large-scale study. Small-scale studies support that dietary acid reduction is kidney-protective, including when done with base-inducing foods like fruits and vegetables. We review these studies in light of current kidney-protective recommendations. Animal models of CKD show that acid-inducing dietary protein exacerbates and base-inducing protein ameliorates nephropathy progression, and that increased intake of acid-inducing but not base-inducing dietary protein exacerbates progression. Clinical studies show that dietary acid reduction with Na-based alkali reduces kidney injury and slows nephropathy progression in patients with CKD and reduced glomerular filtration rate (GFR); base-inducing fruits and vegetables reduce kidney injury in patients with reduced GFR; and base-inducing fruits and vegetables improve metabolic acidosis in CKD. Protein type rather than amount might more importantly affect nephropathy progression. Base-inducing foods might be another way to reduce dietary acid, a strategy shown in small studies to slow nephropathy progression. Further studies will determine if CKD patients should be given base-inducing food as part of their management.

10-Hydroxy-2-decenoic Acid, the Major Lipid Component of Royal Jelly, Extends the Lifespan of Caenorhabditis elegans through Dietary Restriction and Target of Rapamycin Signaling

OpenAIRE

Honda, Yoko; Araki, Yoko; Hata, Taketoshi; Ichihara, Kenji; Ito, Masafumi; Tanaka, Masashi; Honda, Shuji

2015-01-01

Royal jelly (RJ) produced by honeybees has been reported to possess diverse health-beneficial properties and has been implicated to have a function in longevity across diverse species as well as honeybees. 10-Hydroxy-2-decenoic acid (10-HDA), the major lipid component of RJ produced by honeybees, was previously shown to increase the lifespan of Caenorhabditis elegans. The objective of this study is to elucidate signaling pathways that are involved in the lifespan extension by 10-HDA. 10-HDA f...

Polyphenol-Rich Diets Exacerbate AMPK-Mediated Autophagy, Decreasing Proliferation of Mosquito Midgut Microbiota, and Extending Vector Lifespan.

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Rodrigo Dutra Nunes

2016-10-01

Full Text Available Mosquitoes feed on plant-derived fluids such as nectar and sap and are exposed to bioactive molecules found in this dietary source. However, the role of such molecules on mosquito vectorial capacity is unknown. Weather has been recognized as a major determinant of the spread of dengue, and plants under abiotic stress increase their production of polyphenols.Here, we show that including polyphenols in mosquito meals promoted the activation of AMP-dependent protein kinase (AMPK. AMPK positively regulated midgut autophagy leading to a decrease in bacterial proliferation and an increase in vector lifespan. Suppression of AMPK activity resulted in a 6-fold increase in midgut microbiota. Similarly, inhibition of polyphenol-induced autophagy induced an 8-fold increase in bacterial proliferation. Mosquitoes maintained on the polyphenol diet were readily infected by dengue virus.The present findings uncover a new direct route by which exacerbation of autophagy through activation of the AMPK pathway leads to a more efficient control of mosquito midgut microbiota and increases the average mosquito lifespan. Our results suggest for the first time that the polyphenol content and availability of the surrounding vegetation may increase the population of mosquitoes prone to infection with arboviruses.

Epigenetic aging signatures in mice livers are slowed by dwarfism, calorie restriction and rapamycin treatment.

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Wang, Tina; Tsui, Brian; Kreisberg, Jason F; Robertson, Neil A; Gross, Andrew M; Yu, Michael Ku; Carter, Hannah; Brown-Borg, Holly M; Adams, Peter D; Ideker, Trey

2017-03-28

Global but predictable changes impact the DNA methylome as we age, acting as a type of molecular clock. This clock can be hastened by conditions that decrease lifespan, raising the question of whether it can also be slowed, for example, by conditions that increase lifespan. Mice are particularly appealing organisms for studies of mammalian aging; however, epigenetic clocks have thus far been formulated only in humans. We first examined whether mice and humans experience similar patterns of change in the methylome with age. We found moderate conservation of CpG sites for which methylation is altered with age, with both species showing an increase in methylome disorder during aging. Based on this analysis, we formulated an epigenetic-aging model in mice using the liver methylomes of 107 mice from 0.2 to 26.0 months old. To examine whether epigenetic aging signatures are slowed by longevity-promoting interventions, we analyzed 28 additional methylomes from mice subjected to lifespan-extending conditions, including Prop1 df/df dwarfism, calorie restriction or dietary rapamycin. We found that mice treated with these lifespan-extending interventions were significantly younger in epigenetic age than their untreated, wild-type age-matched controls. This study shows that lifespan-extending conditions can slow molecular changes associated with an epigenetic clock in mice livers.

Gender differences in depression and anxiety across the adult lifespan: the role of psychosocial mediators.

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Leach, Liana S; Christensen, Helen; Mackinnon, Andrew J; Windsor, Timothy D; Butterworth, Peter

2008-12-01

There is robust epidemiological and clinical evidence that a greater number of women than men experience depression and anxiety. This study investigated a number of socio-demographic, health and lifestyle, psychological and social factors as possible mediators for the gender difference in depression and anxiety in three cohorts (20-24, 40-44, 60-64). Responses were from a representative, community based survey (n = 7,485) conducted in Canberra and Queanbeyan (NSW), in Australia. Depression and anxiety were measured using the self-report Goldberg Anxiety and Depression Scales. The analyses initially identified gender differences in the potential mediators, followed by univariate and multivariate mediation models. The results indicated several shared mediators for depression and anxiety across the three age groups including: childhood adversity, mastery, behavioural inhibition, ruminative style, neuroticism, physical health, physical activity, and perceived interpersonal and employment problems. There was a decrease in the number of social mediators as age increased. The multivariate models accounted for gender differences in both conditions for all age groups, except for anxiety in the 20-24 years old. This suggests further important unmeasured mediators for this age group. These findings add to the literature surrounding gender differences in depression and anxiety, and provide a basis for future research exploring variation in these gender disparities over the adult lifespan.

The Relationship Between Social Support and Adherence of Dietary and Fluids Restrictions among Hemodialysis Patients in Iran

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Shahnaz Ahrari

2014-02-01

Full Text Available Introduction: Patient’s noncompliance dietary and fluids intake can lead to a build-up of toxic fluids and metabolic end-products in the blood stream which may result in an increased morbidity and premature death. The aim of the study is investigate relationship between the social support and adherence to dietary and fluid restrictions in hemodialysis patients. Methods: In this correlational study upon 237 hemodialysis patients, the data was collected with the dialysis diet and fluids non-adherences hemodialysis questionnaire (DDFQ, and the multidimensional scale of perceived Social Support (MSP. Interdialytic weight gain, predialytic serum potassium levels, and predialytic serum phosphate levels was considered as biochemical indicators of dietary and fluid adherence. Data were analyzed by SPSS Ver.11.5. Results: About 41.1% of patients reported non-adherence to diet and 45.2% of them reported non-adherence to fluid. Frequency of non-adherence to fluid was more common in patients. The highest level of perceived support was the family support 11.19 (1.34. There was a significant relationship between social support and adherence to dietary and fluid restrictions. Noncompliances to dietary and fluid restrictions were related to laboratory results. Conclusion: This way those patients who more supported had more adherences of diet and fluid restrictions and had lower level of phosphorus and potassium in laboratory results. Nurses have the main role to identify different methods providing social support for patients, also to encourage the families to support their hemodialysis patients.

Intermittent food restriction initiated late in life prolongs lifespan and retards the onset of age-related markers in the annual fish Nothobranchius guentheri.

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Wang, Xia; Du, Xiaoyuan; Zhou, Yang; Wang, Su; Su, Feng; Zhang, Shicui

2017-06-01

Two of the most studied and widely accepted conjectures on possible aging mechanisms are the oxidative stress hypothesis and the insulin/insulin-like growth factor 1 (IGF-1) signaling (IIS) pathway. Intermittent fasting (IF) is known to modulate aging and to prolong lifespan in a variety of organisms, but the mechanisms are still under debate. In this study, we first demonstrated that late-onset two consecutive days a week fasting, a form of IF, termed intermittent food restriction (IFR), exhibited a time-dependent effect, and long-term late-onset IFR extended the mean lifespan and maximum lifespan by approximately 3.5 and 3 weeks, respectively, in the annual fish Nothobranchius guentheri. We also showed that IFR reduced the accumulation of lipofuscin in the gills and the protein oxidation and lipid peroxidation levels in the muscles. Moreover, IFR was able to enhance the activities of antioxidant enzymes catalase, glutathione peroxidase, and superoxide dismutase in the fish. Finally, IFR was also able to decelerate the decrease of SirT1 and Foxo3A, but accelerate the decrease of IGF-1. Collectively, our findings suggest that late-onset IFR can retard the onset of age-related markers, and prolong the lifespan of the aging fish, via a synergistic action of an anti-oxidant system and the IIS pathway. It also proposes that the combined assessment of anti-oxidant system and IIS pathway will contribute to providing a more comprehensive view of anti-aging process.

Protective effects of short-term dietary restriction in surgical stress and chemotherapy.

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Brandhorst, Sebastian; Harputlugil, Eylul; Mitchell, James R; Longo, Valter D

2017-10-01

Reduced caloric intake including fasting, as well as the dietary composition or the timing of food intake, impact longevity, likely through a modification in the onset or the severity of chronic aging-related diseases such as cancer. As with pre- and post-operative dietary recommendations, evidence-based nutritional advice from healthcare professionals during and after cancer treatment is often vague or conflicting. We hypothesize that preventive dietary recommendations can help in the context of both chronic cancer treatment efficacy and the avoidance of development of secondary malignancies, as well as in the context of protection from the acute stress of surgery. In this perspective review, we will discuss the latest findings on the potential role of short-term dietary restriction in cancer treatment and improvement of surgical outcome. Copyright © 2017. Published by Elsevier B.V.

Effect of Dietary Restriction and Subsequent Re-Alimentation on the Transcriptional Profile of Bovine Skeletal Muscle.

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Keogh, Kate; Kenny, David A; Cormican, Paul; McCabe, Matthew S; Kelly, Alan K; Waters, Sinead M

2016-01-01

Compensatory growth (CG), an accelerated growth phenomenon which occurs following a period of dietary restriction is exploited worldwide in animal production systems as a method to lower feed costs. However the molecular mechanisms regulated CG expression remain to be elucidated fully. This study aimed to uncover the underlying biology regulating CG in cattle, through an examination of skeletal muscle transcriptional profiles utilising next generation mRNA sequencing technology. Twenty Holstein Friesian bulls were fed either a restricted diet for 125 days, with a target growth rate of 0.6 kg/day (Period 1), following which they were allowed feed ad libitum for a further 55 days (Period 2) or fed ad libitum for the entirety of the trial. M. longissimus dorsi biopsies were harvested from all bulls on days 120 and 15 of periods 1 and 2 respectively and RNAseq analysis was performed. During re-alimentation in Period 2, previously restricted animals displayed CG, growing at 1.8 times the rate of the ad libitum control animals. Compensating animals were also more feed efficient during re-alimentation and compensated for 48% of their previous dietary restriction. 1,430 and 940 genes were identified as significantly differentially expressed (Benjamini Hochberg adjusted P < 0.1) in periods 1 and 2 respectively. Additionally, 2,237 genes were differentially expressed in animals undergoing CG relative to dietary restriction. Dietary restriction in Period 1 was associated with altered expression of genes involved in lipid metabolism and energy production. CG expression in Period 2 occurred in association with greater expression of genes involved in cellular function and organisation. This study highlights some of the molecular mechanisms regulating CG in cattle. Differentially expressed genes identified are potential candidate genes for the identification of biomarkers for CG and feed efficiency, which may be incorporated into future breeding programmes.

Effect of Dietary Restriction and Subsequent Re-Alimentation on the Transcriptional Profile of Bovine Skeletal Muscle.

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Kate Keogh

Full Text Available Compensatory growth (CG, an accelerated growth phenomenon which occurs following a period of dietary restriction is exploited worldwide in animal production systems as a method to lower feed costs. However the molecular mechanisms regulated CG expression remain to be elucidated fully. This study aimed to uncover the underlying biology regulating CG in cattle, through an examination of skeletal muscle transcriptional profiles utilising next generation mRNA sequencing technology. Twenty Holstein Friesian bulls were fed either a restricted diet for 125 days, with a target growth rate of 0.6 kg/day (Period 1, following which they were allowed feed ad libitum for a further 55 days (Period 2 or fed ad libitum for the entirety of the trial. M. longissimus dorsi biopsies were harvested from all bulls on days 120 and 15 of periods 1 and 2 respectively and RNAseq analysis was performed. During re-alimentation in Period 2, previously restricted animals displayed CG, growing at 1.8 times the rate of the ad libitum control animals. Compensating animals were also more feed efficient during re-alimentation and compensated for 48% of their previous dietary restriction. 1,430 and 940 genes were identified as significantly differentially expressed (Benjamini Hochberg adjusted P < 0.1 in periods 1 and 2 respectively. Additionally, 2,237 genes were differentially expressed in animals undergoing CG relative to dietary restriction. Dietary restriction in Period 1 was associated with altered expression of genes involved in lipid metabolism and energy production. CG expression in Period 2 occurred in association with greater expression of genes involved in cellular function and organisation. This study highlights some of the molecular mechanisms regulating CG in cattle. Differentially expressed genes identified are potential candidate genes for the identification of biomarkers for CG and feed efficiency, which may be incorporated into future breeding programmes.

Protein restriction and cancer.

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Yin, Jie; Ren, Wenkai; Huang, Xingguo; Li, Tiejun; Yin, Yulong

2018-03-26

Protein restriction without malnutrition is currently an effective nutritional intervention known to prevent diseases and promote health span from yeast to human. Recently, low protein diets are reported to be associated with lowered cancer incidence and mortality risk of cancers in human. In murine models, protein restriction inhibits tumor growth via mTOR signaling pathway. IGF-1, amino acid metabolic programing, FGF21, and autophagy may also serve as potential mechanisms of protein restriction mediated cancer prevention. Together, dietary intervention aimed at reducing protein intake can be beneficial and has the potential to be widely adopted and effective in preventing and treating cancers. Copyright © 2018 Elsevier B.V. All rights reserved.

Insulin secretion and signaling in response to dietary restriction and subsequent re-alimentation in cattle.

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Keogh, Kate; Kenny, David A; Kelly, Alan K; Waters, Sinéad M

2015-08-01

The objectives of this study were to examine systemic insulin response to a glucose tolerance test (GTT) and transcript abundance of genes of the insulin signaling pathway in skeletal muscle, during both dietary restriction and re-alimentation-induced compensatory growth. Holstein Friesian bulls were blocked to one of two groups: 1) restricted feed allowance for 125 days (period 1) (RES, n = 15) followed by ad libitum feeding for 55 days (period 2) or 2) ad libitum access to feed throughout (periods 1 and 2) (ADLIB, n = 15). On days 90 and 36 of periods 1 and 2, respectively, a GTT was performed. M. longissimus dorsi biopsies were harvested from all bulls on days 120 and 15 of periods 1 and 2, respectively, and RNA-Seq analysis was performed. RES displayed a lower growth rate during period 1 (RES: 0.6 kg/day, ADLIB: 1.9 kg/day; P alimentation (RES: 2.5 kg/day, ADLIB: 1.4 kg/day; P alimentation (P > 0.05). Genes differentially expressed in the insulin signaling pathway suggested a greater sensitivity to insulin in skeletal muscle, with pleiotropic effects of insulin signaling interrupted during dietary restriction. Collectively, these results indicate increased sensitivity to glucose clearance and skeletal muscle insulin signaling during dietary restriction; however, no overall role for insulin was apparent in expressing compensatory growth. Copyright © 2015 the American Physiological Society.

Role of HIV-2 envelope in Lv2-mediated restriction

International Nuclear Information System (INIS)

Reuter, Sandra; Kaumanns, Patrick; Buschhorn, Sabine B.; Dittmar, Matthias T.

2005-01-01

We have characterized envelope protein pseudotyped HIV-2 particles derived from two HIV-2 isolates termed prCBL23 and CBL23 in order to define the role of the envelope protein for the Lv2-mediated restriction to infection. Previously, it has been described that the primary isolate prCBL23 is restricted to infection of several human cell types, whereas the T cell line adapted isolate CBL23 is not restricted in these cell types. Molecular cloning of the two isolates revealed that the env and the gag gene are responsible for the observed phenotype and that this restriction is mediated by Lv2, which is distinct from Ref1/Lv1 (Schmitz, C., Marchant, D., Neil, S.J., Aubin, K., Reuter, S., Dittmar, M.T., McKnight, A., Kizhatil, K., Albritton, L.M., 2004. Lv2, a novel postentry restriction, is mediated by both capsid and envelope. J. Virol. 78 (4), 2006-2016). We generated pseudotyped viruses consisting of HIV-2 (ROD-AΔenv-GFP, ROD-AΔenv-RFP, or ROD-AΔenv-REN) and the prCBL23 or CBL23 envelope proteins as well as chimeric proteins between these envelopes. We demonstrate that a single amino acid exchange at position 74 in the surface unit of CBL23-Env confers restriction to infection. This single point mutation causes tighter CD4 binding, resulting in a less efficient fusion into the cytosol of the restricted cell line. Prevention of endosome formation and prevention of endosome acidification enhance infectivity of the restricted particles for GHOST/X4 cells indicating a degradative lysosomal pathway as a cause for the reduced cytosolic entry. The described restriction to infection of the primary isolate prCBL23 is therefore largely caused by an entry defect. A remaining restriction to infection (19-fold) is preserved when endosomal acidification is prevented. This restriction to infection is also dependent on the presence of the point mutation at position 74 (G74E)

Effects of fluctuating temperature and food availability on reproduction and lifespan

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Schwartz, Tonia S.; Pearson, Phillip; Dawson, John; Allison, David B.; Gohlke, Julia M.

2016-01-01

Experimental studies on energetics and aging often remove two major factors that in part regulate the energy budget in a normal healthy individual: reproduction and fluctuating environmental conditions that challenge homeostasis. Here we use the cyclical parthenogenetic Daphnia pulex to evaluate the role of a fluctuating thermal environment on both reproduction and lifespan across six food concentrations. We test the hypotheses that (1) caloric restriction extends lifespan; (2) maximal reprod...

Molar macrowear reveals Neanderthal eco-geographic dietary variation.

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Luca Fiorenza

Full Text Available Neanderthal diets are reported to be based mainly on the consumption of large and medium sized herbivores, while the exploitation of other food types including plants has also been demonstrated. Though some studies conclude that early Homo sapiens were active hunters, the analyses of faunal assemblages, stone tool technologies and stable isotopic studies indicate that they exploited broader dietary resources than Neanderthals. Whereas previous studies assume taxon-specific dietary specializations, we suggest here that the diet of both Neanderthals and early Homo sapiens is determined by ecological conditions. We analyzed molar wear patterns using occlusal fingerprint analysis derived from optical 3D topometry. Molar macrowear accumulates during the lifespan of an individual and thus reflects diet over long periods. Neanderthal and early Homo sapiens maxillary molar macrowear indicates strong eco-geographic dietary variation independent of taxonomic affinities. Based on comparisons with modern hunter-gatherer populations with known diets, Neanderthals as well as early Homo sapiens show high dietary variability in Mediterranean evergreen habitats but a more restricted diet in upper latitude steppe/coniferous forest environments, suggesting a significant consumption of high protein meat resources.

Dietary non-esterified oleic Acid decreases the jejunal levels of anorectic N-acylethanolamines

DEFF Research Database (Denmark)

Diep, Thi Ai; Madsen, Andreas N; Krogh-Hansen, Sandra

2014-01-01

mice respond to dietary fat (olive oil) by reducing levels of anorectic NAEs, and 3) whether dietary non-esterified oleic acid also can decrease levels of anorectic NAEs in mice. We are searching for the fat sensor in the intestine, which mediates the decreased levels of anorectic NAEs. METHODS: Male...... of anorectic NAEs in mice. CONCLUSIONS: These results suggest that the down-regulation of the jejunal level of anorectic NAEs by dietary fat is not restricted to rats, and that the fatty acid component oleic acid, in dietary olive oil may be sufficient to mediate this regulation. Thus, a fatty acid sensor may...

A reduction in age-enhanced gluconeogenesis extends lifespan.

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Hachinohe, Mayumi; Yamane, Midori; Akazawa, Daiki; Ohsawa, Kazuhiro; Ohno, Mayumi; Terashita, Yuzu; Masumoto, Hiroshi

2013-01-01

The regulation of energy metabolism, such as calorie restriction (CR), is a major determinant of cellular longevity. Although augmented gluconeogenesis is known to occur in aged yeast cells, the role of enhanced gluconeogenesis in aged cells remains undefined. Here, we show that age-enhanced gluconeogenesis is suppressed by the deletion of the tdh2 gene, which encodes glyceraldehyde-3-phosphate dehydrogenase (GAPDH), a protein that is involved in both glycolysis and gluconeogenesis in yeast cells. The deletion of TDH2 restores the chronological lifespan of cells with deletions of both the HST3 and HST4 genes, which encode yeast sirtuins, and represses the activation of gluconeogenesis. Furthermore, the tdh2 gene deletion can extend the replicative lifespan in a CR pathway-dependent manner. These findings demonstrate that the repression of enhanced gluconeogenesis effectively extends the cellular lifespan.

A reduction in age-enhanced gluconeogenesis extends lifespan.

Directory of Open Access Journals (Sweden)

Mayumi Hachinohe

Full Text Available The regulation of energy metabolism, such as calorie restriction (CR, is a major determinant of cellular longevity. Although augmented gluconeogenesis is known to occur in aged yeast cells, the role of enhanced gluconeogenesis in aged cells remains undefined. Here, we show that age-enhanced gluconeogenesis is suppressed by the deletion of the tdh2 gene, which encodes glyceraldehyde-3-phosphate dehydrogenase (GAPDH, a protein that is involved in both glycolysis and gluconeogenesis in yeast cells. The deletion of TDH2 restores the chronological lifespan of cells with deletions of both the HST3 and HST4 genes, which encode yeast sirtuins, and represses the activation of gluconeogenesis. Furthermore, the tdh2 gene deletion can extend the replicative lifespan in a CR pathway-dependent manner. These findings demonstrate that the repression of enhanced gluconeogenesis effectively extends the cellular lifespan.

Modified lingguizhugan decoction incorporated with dietary restriction and exercise ameliorates hyperglycemia, hyperlipidemia and hypertension in a rat model of the metabolic syndrome.

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Yao, Limei; Wei, Jingjing; Shi, Si; Guo, Kunbin; Wang, Xiangyu; Wang, Qi; Chen, Dingsheng; Li, Weirong

2017-02-28

Modified Lingguizhugan Decoction (MLD) came from famous Chinese medicine Linggui Zhugan Decoction. The MLD is used for the treatment of metabolic syndrome in the clinical setting. Our study focuses on the comprehensive treatment of MLD incorporated with dietary restriction and exercise in a rat model of the metabolic syndrome (MS). Rats were divided into five groups: control group (Cont), high-fat diet group (HFD), high-fat diet incorporated with dietary restriction group (HFD-DR), exercise incorporated with dietary restriction group (HFD-DR-Ex) and MLD incorporated with dietary restriction and exercise group (HFD-DR-Ex-MLD). Treatments were conducted for 1 week after feeding high-fat diet for 12 weeks. The effects of treatments on high fat diet-induced obesity, hyperglycemia, hyperlipidemia, hypertension, hepatic injury and insulin resistance in rats of MS were examined. In addition, the tumor necrosis factor-α (TNF-α), leptin and protein kinase B (PKB) in rats serum and liver were also examined by enzyme-linked immunosorbent assay (ELISA). After a week's intervention by dietary restriction, dietary restriction incorporated with exercise or MLD, compared with HFD rats, the relative weight of liver and fat, levels of triglyceride, total cholesterol, low-density lipoprotein, free fatty acid, aspartate aminotransferase, glutamic-pyruvic transaminase and alkaline phosphatase, insulin, were significantly decreased (p exercise treatment exhibit effects in alleviating high-fat diet-induced obesity, hyperglycemia, hyperlipidemia, hypertension, hepatic injury and insulin resistance, which are possibly due to the down-regulation of TNF-α, leptin and PKB.

Role of Dietary Restriction in the Prevention of Infection in Leukaemia

African Journals Online (AJOL)

1974-09-28

Sep 28, 1974 ... to compare the results with the bacterial content of cooked foods as supplied in a general medical ward in our hospital. in order to assess the validity of strict dietary restriction. METHODS. A spot test sample of a variety of cooked food was taken from the food trolley usually used for distribution of meals to the ...

Regulation of longevity and oxidative stress by nutritional interventions: role of methionine restriction.

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Sanchez-Roman, Ines; Barja, Gustavo

2013-10-01

Comparative studies indicate that long-lived mammals have low rates of mitochondrial reactive oxygen species production (mtROSp) and oxidative damage in their mitochondrial DNA (mtDNA). Dietary restriction (DR), around 40%, extends the mean and maximum life span of a wide range of species and lowers mtROSp and oxidative damage to mtDNA, which supports the mitochondrial free radical theory of aging (MFRTA). Regarding the dietary factor responsible for the life extension effect of DR, neither carbohydrate nor lipid restriction seems to modify maximum longevity. However protein restriction (PR) and methionine restriction (at least 80% MetR) increase maximum lifespan in rats and mice. Interestingly, only 7weeks of 40% PR (at least in liver) or 40% MetR (in all the studied organs, heart, brain, liver or kidney) is enough to decrease mtROSp and oxidative damage to mtDNA in rats, whereas neither carbohydrate nor lipid restriction changes these parameters. In addition, old rats also conserve the capacity to respond to 7weeks of 40% MetR with these beneficial changes. Most importantly, 40% MetR, differing from what happens during both 40% DR and 80% MetR, does not decrease growth rate and body size of rats. All the available studies suggest that the decrease in methionine ingestion that occurs during DR is responsible for part of the aging-delaying effect of this intervention likely through the decrease of mtROSp and ensuing DNA damage that it exerts. We conclude that lowering mtROS generation is a conserved mechanism, shared by long-lived species and dietary, protein, and methionine restricted animals, that decreases damage to macromolecules situated near the complex I mtROS generator, especially mtDNA. This would decrease the accumulation rate of somatic mutations in mtDNA and maybe finally also in nuclear DNA. Copyright © 2013 Elsevier Inc. All rights reserved.

Differences in Sirtuin Regulation in Response to Calorie Restriction in Cryptococcus neoformans.

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Bouklas, Tejas; Masone, Lindsey; Fries, Bettina C

2018-02-18

Cryptococcus neoformans successfully replicates in low glucose in infected patients. In the serotype A strain, H99, growth in this condition prolongs lifespan regulated by SIR2, and can be modulated with SIR2-specific drugs. Previous studies show that lifespan modulation of a cryptococcal population affects its sensitivity to antifungals, and survival in an infection model. Sirtuins and their role in longevity are conserved among fungi; however, the effect of glucose starvation is not confirmed even in Saccharomyces cerevisiae. Lifespan analysis of C. neoformans strains in low glucose showed that 37.5% exhibited pro-longevity, and lifespan of a serotype D strain, RC2, was shortened. Transcriptome comparison of H99 and RC2 under calorie restriction demonstrated differences, confirmed by real-time PCR showing that SIR2 , TOR1 , SCH9 , and PKA1 expression correlated with lifespan response to calorie restriction. As expected, RC2 -sir2 Δ cells exhibited a shortened lifespan, which was reconstituted. However, shortened lifespan from calorie restriction was independent of SIR2 . In contrast to H99 but consistent with altered SIR2 regulation, SIR2 -specific drugs did not affect outcome of RC2 infection. These data suggest that SIR2 regulation and response to calorie restriction varies in C. neoformans, which should be considered when Sirtuins are investigated as potential therapy targets for fungal infections.

Patterns of intraspecific variability in the response to caloric restriction

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Gribble, Kristin E.; Kaido, Oksana; Jarvis, George; Mark Welch, David B.

2014-01-01

Caloric restriction (CR) is cited as the most robust means of increasing lifespan across a range of taxa, yet there is a high degree of variability in the response to CR, both within and between species. To examine the intraspecific evolutionary conservation of lifespan extension by CR, we tested the effects of chronic caloric restriction (CCR) at multiple food levels and of intermittent fasting (IF) in twelve isolates from the Brachionus plicatilis species complex of monogonont rotifers. While CCR generally increased or did not change lifespan and total fecundity, IF caused increased, unchanged, or decreased lifespan, depending upon the isolate, and decreased total fecundity in all but one isolate. Lifespan under ad libitum (AL) feeding varied among isolates and predicted the lifespan response to CR: longer-lived isolates under AL were less likely to have a significant increase in lifespan under CCR and were more likely to have a significantly shortened lifespan under IF. Lifespan under AL conditions and the response to CR were not correlated with hydroperiodicity of native habitat or with time in culture. Lack of trade-off between lifespan and fecundity under CCR, and differences in lifespan and fecundity under CCR and IF, even when average food intake was similar, suggest that longevity changes are not always directly determined by energy intake and that CCR and IF regimens extend lifespan through diverse genetic mechanisms. PMID:24384399

Biochemical responses to dietary α-linolenic acid restriction proceed differently among brain regions in mice.

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Miyazawa, Daisuke; Yasui, Yuko; Yamada, Kazuyo; Ohara, Naoki; Okuyama, Harumi

2011-08-01

Previously, we noted that the dietary restriction of α-linolenic acid (ALA, n-3) for 4 weeks after weaning brought about significant decreases in the BDNF content and p38 MAPK activity in the striatum of mice, but not in the other regions of the brain, compared with an ALA- and linoleic acid (LNA, n-6)-adequate diet. In this study, we examined whether a prolonged dietary manipulation induces biochemical changes in other regions of the brain as well. Mice were fed a safflower oil (SAF) diet (ALA-restricted, LNA-adequate) or a perilla oil (PER) diet (containing adequate amounts of ALA and LNA) for 8 weeks from weaning. The docosahexaenoic acid (DHA, 22:6n-3) contents and p38 MAPK activities in the cerebral cortex, striatum and hippocampus were significantly lower in the SAF group. The BDNF contents and protein kinase C (PKC) activities in the cerebral cortex as well as in the striatum, but not in the hippocampus, were significantly lower in the SAF group. These data indicate that the biochemical changes induced by the dietary restriction of ALA have a time lag in the striatum and cortex, suggesting that the signal is transmitted through decreased p38 MAPK activity and BDNF content and ultimately decreased PKC activity.

Epigenetic regulation of caloric restriction in aging

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Daniel Michael

2011-08-01

Full Text Available Abstract The molecular mechanisms of aging are the subject of much research and have facilitated potential interventions to delay aging and aging-related degenerative diseases in humans. The aging process is frequently affected by environmental factors, and caloric restriction is by far the most effective and established environmental manipulation for extending lifespan in various animal models. However, the precise mechanisms by which caloric restriction affects lifespan are still not clear. Epigenetic mechanisms have recently been recognized as major contributors to nutrition-related longevity and aging control. Two primary epigenetic codes, DNA methylation and histone modification, are believed to dynamically influence chromatin structure, resulting in expression changes of relevant genes. In this review, we assess the current advances in epigenetic regulation in response to caloric restriction and how this affects cellular senescence, aging and potential extension of a healthy lifespan in humans. Enhanced understanding of the important role of epigenetics in the control of the aging process through caloric restriction may lead to clinical advances in the prevention and therapy of human aging-associated diseases.

Age- and calorie-independent life span extension from dietary restriction by bacterial deprivation in Caenorhabditis elegans

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Sager Jennifer

2008-05-01

Full Text Available Abstract Background Dietary restriction (DR increases life span and delays age-associated disease in many organisms. The mechanism by which DR enhances longevity is not well understood. Results Using bacterial food deprivation as a means of DR in C. elegans, we show that transient DR confers long-term benefits including stress resistance and increased longevity. Consistent with studies in the fruit fly and in mice, we demonstrate that DR also enhances survival when initiated late in life. DR by bacterial food deprivation significantly increases life span in worms when initiated as late as 24 days of adulthood, an age at which greater than 50% of the cohort have died. These survival benefits are, at least partially, independent of food consumption, as control fed animals are no longer consuming bacterial food at this advanced age. Animals separated from the bacterial lawn by a barrier of solid agar have a life span intermediate between control fed and food restricted animals. Thus, we find that life span extension from bacterial deprivation can be partially suppressed by a diffusible component of the bacterial food source, suggesting a calorie-independent mechanism for life span extension by dietary restriction. Conclusion Based on these findings, we propose that dietary restriction by bacterial deprivation increases longevity in C. elegans by a combination of reduced food consumption and decreased food sensing.

Metabolomics of Dietary Fatty Acid Restriction in Patients with Phenylketonuria

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Mütze, Ulrike; Beblo, Skadi; Kortz, Linda; Matthies, Claudia; Koletzko, Berthold; Bruegel, Mathias; Rohde, Carmen; Thiery, Joachim; Kiess, Wieland; Ceglarek, Uta

2012-01-01

Background Patients with phenylketonuria (PKU) have to follow a lifelong phenylalanine restricted diet. This type of diet markedly reduces the intake of saturated and unsaturated fatty acids especially long chain polyunsaturated fatty acids (LC-PUFA). Long-chain saturated fatty acids are substrates of mitochondrial fatty acid oxidation for acetyl-CoA production. LC-PUFA are discussed to affect inflammatory and haemostaseological processes in health and disease. The influence of the long term PKU diet on fatty acid metabolism with a special focus on platelet eicosanoid metabolism has been investigated in the study presented here. Methodology/Principal Findings 12 children with PKU under good metabolic control and 8 healthy controls were included. Activated fatty acids (acylcarnitines C6–C18) in dried blood and the cholesterol metabolism in serum were analyzed by liquid chromatographic tandem mass spectrometry (LC-MS/MS). Fatty acid composition of plasma glycerophospholipids was determined by gas chromatography. LC-PUFA metabolites were analyzed in supernatants by LC-MS/MS before and after platelet activation and aggregation using a standardized protocol. Patients with PKU had significantly lower free carnitine and lower activated fatty acids in dried blood compared to controls. Phytosterols as marker of cholesterol (re-) absorption were not influenced by the dietary fatty acid restriction. Fatty acid composition in glycerophospholipids was comparable to that of healthy controls. However, patients with PKU showed significantly increased concentrations of y-linolenic acid (C18:3n-6) a precursor of arachidonic acid. In the PKU patients significantly higher platelet counts were observed. After activation with collagen platelet aggregation and thromboxane B2 and thromboxane B3 release did not differ from that of healthy controls. Conclusion/Significance Long-term dietary fatty acid restriction influenced the intermediates of mitochondrial beta-oxidation. No functional

Metabolomics of dietary fatty acid restriction in patients with phenylketonuria.

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Ulrike Mütze

Full Text Available BACKGROUND: Patients with phenylketonuria (PKU have to follow a lifelong phenylalanine restricted diet. This type of diet markedly reduces the intake of saturated and unsaturated fatty acids especially long chain polyunsaturated fatty acids (LC-PUFA. Long-chain saturated fatty acids are substrates of mitochondrial fatty acid oxidation for acetyl-CoA production. LC-PUFA are discussed to affect inflammatory and haemostaseological processes in health and disease. The influence of the long term PKU diet on fatty acid metabolism with a special focus on platelet eicosanoid metabolism has been investigated in the study presented here. METHODOLOGY/PRINCIPAL FINDINGS: 12 children with PKU under good metabolic control and 8 healthy controls were included. Activated fatty acids (acylcarnitines C6-C18 in dried blood and the cholesterol metabolism in serum were analyzed by liquid chromatographic tandem mass spectrometry (LC-MS/MS. Fatty acid composition of plasma glycerophospholipids was determined by gas chromatography. LC-PUFA metabolites were analyzed in supernatants by LC-MS/MS before and after platelet activation and aggregation using a standardized protocol. Patients with PKU had significantly lower free carnitine and lower activated fatty acids in dried blood compared to controls. Phytosterols as marker of cholesterol (re- absorption were not influenced by the dietary fatty acid restriction. Fatty acid composition in glycerophospholipids was comparable to that of healthy controls. However, patients with PKU showed significantly increased concentrations of y-linolenic acid (C18:3n-6 a precursor of arachidonic acid. In the PKU patients significantly higher platelet counts were observed. After activation with collagen platelet aggregation and thromboxane B(2 and thromboxane B(3 release did not differ from that of healthy controls. CONCLUSION/SIGNIFICANCE: Long-term dietary fatty acid restriction influenced the intermediates of mitochondrial beta

Myricetin-Mediated Lifespan Extension in Caenorhabditis elegans Is Modulated by DAF-16

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Wim Wätjen

2013-06-01

Full Text Available Myricetin is a naturally occurring flavonol found in many plant based food sources. It increases the lifespan of Caenorhabditis elegans, but the molecular mechanisms are not yet fully understood. We have investigated the impact of this flavonoid on the transcription factors DAF-16 (C. elegans FoxO homologue and SKN-1 (Nrf2 homologue, which have crucial functions in the regulation of ageing. Myricetin is rapidly assimilated by the nematode, causes a nuclear translocation of DAF-16 but not of SKN-1, and finally prolongs the mean adult lifespan of C. elegans by 32.9%. The lifespan prolongation was associated with a decrease in the accumulation of reactive oxygen species (ROS detected by DCF. Myricetin also decreases the formation of lipofuscin, a pigment consisting of highly oxidized and cross-linked proteins that is considered as a biomarker of ageing in diverse species. The lifespan extension was completely abolished in a daf-16 loss-of-function mutant strain (CF1038. Consistently with this result, myricetin was also not able to diminish stress-induced ROS accumulation in the mutant. These results strongly indicate that the pro-longevity effect of myricetin is dependent on DAF-16 and not on direct anti-oxidative effects of the flavonoid.

A review of methionine dependency and the role of methionine restriction in cancer growth control and life-span extension.

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Cavuoto, Paul; Fenech, Michael F

2012-10-01

Methionine is an essential amino acid with many key roles in mammalian metabolism such as protein synthesis, methylation of DNA and polyamine synthesis. Restriction of methionine may be an important strategy in cancer growth control particularly in cancers that exhibit dependence on methionine for survival and proliferation. Methionine dependence in cancer may be due to one or a combination of deletions, polymorphisms or alterations in expression of genes in the methionine de novo and salvage pathways. Cancer cells with these defects are unable to regenerate methionine via these pathways. Defects in the metabolism of folate may also contribute to the methionine dependence phenotype in cancer. Selective killing of methionine dependent cancer cells in co-culture with normal cells has been demonstrated using culture media deficient in methionine. Several animal studies utilizing a methionine restricted diet have reported inhibition of cancer growth and extension of a healthy life-span. In humans, vegan diets, which can be low in methionine, may prove to be a useful nutritional strategy in cancer growth control. The development of methioninase which depletes circulating levels of methionine may be another useful strategy in limiting cancer growth. The application of nutritional methionine restriction and methioninase in combination with chemotherapeutic regimens is the current focus of clinical studies. Copyright © 2012 Elsevier Ltd. All rights reserved.

Dietary Restriction Behaviors and Binge Eating in Anorexia Nervosa, Bulimia Nervosa and Binge Eating Disorder: Trans-diagnostic Examination of the Restraint Model.

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Elran-Barak, Roni; Sztainer, Maya; Goldschmidt, Andrea B; Crow, Scott J; Peterson, Carol B; Hill, Laura L; Crosby, Ross D; Powers, Pauline; Mitchell, James E; Le Grange, Daniel

2015-08-01

To compare dietary restriction behaviors among adults with eating disorders involving binge eating, including anorexia nervosa-binge/purge subtype (AN-BE/P), bulimia nervosa (BN), and binge eating disorder (BED), and to examine whether dietary restriction behaviors impact binge eating frequency across diagnoses. Participants included 845 treatment seeking adults (M=30.42+10.76years) who met criteria for DSM-5 AN-BE/P (7.3%;n=62), BN (59.7%;n=504), and BED (33.0%;n=279). All participants self-reported their past and current eating disorder symptoms on the Eating Disorder Questionnaire. Adults with AN-BE/P and BN reported significantly more dietary restriction behaviors (e.g. eating fewer meals per day, higher frequency of fasting, consuming small and low calorie meals) in comparison to adults with BED. Adults with AN-BE/P and BN who reported restricting food intake via eating fewer meals per day had more frequent binge eating episodes. However, adults with BN who reported restricting food intake via eating small meals and low calorie meals had less frequent binge eating episodes. This study provides mixed support for the restraint model by suggesting that not all dietary restriction behaviors are associated with higher levels of binge eating. It may be that adults with BN who report a higher frequency of eating small and low calorie meals display more control over their eating in general, and therefore also have lower frequency of binge eating. Clinicians should assess for dietary restriction behaviors at the start of treatment prior to assuming that all forms of strict dieting and weight control behaviors similarly impact binge eating. Copyright © 2015. Published by Elsevier Ltd.

Dietary restriction alters fine motor function in rats.

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Smith, Lori K; Metz, Gerlinde A

2005-08-07

A number of standard behavioral tasks in animal research utilize food rewards for positive reinforcement. In order to enhance the motivation to participate in these tasks, animals are usually placed on a restricted diet. While dietary restriction (DR) has been shown to have beneficial effects on recovery after brain injury, life span and aging processes, it might also represent a stressor. Since stress can influence a broad range of behaviors, the purpose of this study was to assess whether DR may have similar effects on skilled movement. Adult male Long-Evans rats were trained and tested in a skilled reaching task both prior to and during a mild food restriction regimen that maintained their body weights at 90-95% of baseline weight for eight days. The observations revealed that DR decreased reaching success and increased the number of attempts to grasp a single food pellet. The animals appeared to be more frantic when attempting to reach for food pellets, and the time taken to reach for 20 pellets decreased following the onset of DR. A second experiment investigating behaviors that do not require food rewards, including a ladder rung walking task and an open field test, confirmed that rats on DR display deficits in skilled movements and are hyperactive. These findings suggest that results obtained in motor tasks using food rewards need to be interpreted with caution. The findings are discussed with respect to stress associated with DR.

Dietary -carbamylglutamate and rumen-protected -arginine supplementation ameliorate fetal growth restriction in undernourished ewes.

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Zhang, H; Sun, L W; Wang, Z Y; Deng, M T; Zhang, G M; Guo, R H; Ma, T W; Wang, F

2016-05-01

This study was conducted with an ovine intrauterine growth restriction (IUGR) model to test the hypothesis that dietary -carbamylglutamate (NCG) and rumen-protected -Arg (RP-Arg) supplementation are effective in ameliorating fetal growth restriction in undernourished ewes. Beginning on d 35 of gestation, ewes were fed a diet providing 100% of NRC-recommended nutrient requirements, 50% of NRC recommendations (50% NRC), 50% of NRC recommendations supplemented with 20 g/d RP-Arg (providing 10 g/d of Arg), and 50% of NRC recommendations supplemented with 5 g/d NCG product (providing 2.5 g/d of NCG). On d 110, maternal, fetal, and placental tissues and fluids were collected and weighed. Ewe weights were lower ( ewes compared with adequately fed ewes. Maternal RP-Arg or NCG supplementation did not alter ( = 0.26) maternal BW in nutrient-restricted ewes. Weights of most fetal organs were increased ( ewes compared with 50% NRC-fed ewes. Supplementation of RP-Arg or NCG reduced ( ewes but had no effect on concentrations of lactate and GH. Maternal RP-Arg or NCG supplementation markedly improved ( ewes. These novel results indicate that dietary NCG and RP-Arg supplementation to underfed ewes ameliorated fetal growth restriction, at least in part, by increasing the availability of AA in the conceptus and provide support for its clinical use to ameliorate IUGR in humans and sheep industry production.

Effects of dietary caffeine on mood when rested and sleep restricted.

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James, Jack E; Gregg, M Elizabeth

2004-07-01

Prolonged use of caffeine can lead to physical dependence evidenced by characteristic withdrawal symptoms during abstinence. Debate exists as to whether mood enhancement by caffeine represents a net effect or merely the restoration of abstinence-induced mood decrements. One aim of this study was to determine the net effects on mood of dietary caffeine compared with prolonged abstinence. In addition, the study aimed to determine whether caffeine restores mood degraded by a non-caffeine source, namely, sleep restriction. A double-blind placebo-controlled cross-over design was employed in which 48 male and female volunteers alternated weekly between ingesting placebo and caffeine (1.75 mg/kg) three times daily for 4 consecutive weeks, while being either rested or sleep restricted. Mood was assessed using a computerized version of the profile of mood states (POMS), giving scores for overall mood and six mood dimensions. Gender had small effects on mood, whereas all mood dimensions were markedly adversely affected by sleep restriction. Caffeine had no significant net enhancing effects on mood when participants were rested, and produced no net restorative effects when mood was degraded by sleep restriction. On the contrary, caffeine-induced decrements in mood were observed during both conditions of rest and sleep restriction. Copyright 2004 John Wiley & Sons, Ltd.

Dietary fat and carbohydrates differentially alter insulin sensitivity during caloric restriction.

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Kirk, Erik; Reeds, Dominic N; Finck, Brian N; Mayurranjan, S Mitra; Mayurranjan, Mitra S; Patterson, Bruce W; Klein, Samuel

2009-05-01

We determined the effects of acute and chronic calorie restriction with either a low-fat, high-carbohydrate (HC) diet or a low-carbohydrate (LC) diet on hepatic and skeletal muscle insulin sensitivity. Twenty-two obese subjects (body mass index, 36.5 +/- 0.8 kg/m2) were randomized to an HC (>180 g/day) or LC (vs 8.9% +/- 1.4%; P vs 7.2% +/- 1.4%; P vs 7.9% +/- 1.2%; P < .05). Insulin-mediated glucose uptake did not change at 48 hours but increased similarly in both groups after 7% weight loss (48.4% +/- 14.3%; P < .05). In both groups, insulin-stimulated phosphorylation of c-Jun-N-terminal kinase decreased by 29% +/- 13% and phosphorylation of Akt and insulin receptor substrate 1 increased by 35% +/- 9% and 36% +/- 9%, respectively, after 7% weight loss (all P < .05). Moderate calorie restriction causes temporal changes in liver and skeletal muscle metabolism; 48 hours of calorie restriction affects the liver (IHTG content, hepatic insulin sensitivity, and glucose production), whereas moderate weight loss affects muscle (insulin-mediated glucose uptake and insulin signaling).

Dietary restriction of choline reduces hippocampal acetylcholine release in rats: in vivo microdialysis study.

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Nakamura, A; Suzuki, Y; Umegaki, H; Ikari, H; Tajima, T; Endo, H; Iguchi, A

2001-12-01

We fed rats with a diet deficient in choline for 12 weeks and studied how dietary choline deficiency affected their behavior and their ability to release acetylcholine in discrete regions of rat brain using step-through passive avoidance task and in vivo microdialysis. In comparison with the control, rats fed the choline-deficient diet showed poorer retention of nociceptive memory in the passive avoidance task. Average choline level in cerebrospinal fluid in the choline-deficient group was significantly less (33.1%) than that of control rats. In vivo microdialysis showed no difference in the pattern of acetylcholine release enhanced by intraperitoneal administration of scopolamine hydrochloride (2 mg/kg) in the striatum between the two groups, whereas in the hippocampus, the maximum and subsequent increase of acetylcholine from the baseline by scopolamine injection was significantly lower in the choline-deficient group than in the control. From the results of our study, we speculate that long-term dietary restriction of choline can affect extra- and intracellular sources of substrates required for acetylcholine synthesis, and eventually limit the ability to release acetylcholine in the hippocampus. Reduced capacity to release acetylcholine in the hippocampus implies that the mechanism, maintaining acetylcholine synthesis on increased neuronal demand, may vary in discrete regions of the brain in response to dietary manipulation. The vulnerability of the mechanism in the hippocampus to dietary choline restriction is indicated by impaired mnemonic performance we observed.

The Gcn4 transcription factor reduces protein synthesis capacity and extends yeast lifespan.

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Mittal, Nitish; Guimaraes, Joao C; Gross, Thomas; Schmidt, Alexander; Vina-Vilaseca, Arnau; Nedialkova, Danny D; Aeschimann, Florian; Leidel, Sebastian A; Spang, Anne; Zavolan, Mihaela

2017-09-06

In Saccharomyces cerevisiae, deletion of large ribosomal subunit protein-encoding genes increases the replicative lifespan in a Gcn4-dependent manner. However, how Gcn4, a key transcriptional activator of amino acid biosynthesis genes, increases lifespan, is unknown. Here we show that Gcn4 acts as a repressor of protein synthesis. By analyzing the messenger RNA and protein abundance, ribosome occupancy and protein synthesis rate in various yeast strains, we demonstrate that Gcn4 is sufficient to reduce protein synthesis and increase yeast lifespan. Chromatin immunoprecipitation reveals Gcn4 binding not only at genes that are activated, but also at genes, some encoding ribosomal proteins, that are repressed upon Gcn4 overexpression. The promoters of repressed genes contain Rap1 binding motifs. Our data suggest that Gcn4 is a central regulator of protein synthesis under multiple perturbations, including ribosomal protein gene deletions, calorie restriction, and rapamycin treatment, and provide an explanation for its role in longevity and stress response.The transcription factor Gcn4 is known to regulate yeast amino acid synthesis. Here, the authors show that Gcn4 also acts as a repressor of protein biosynthesis in a range of conditions that enhance yeast lifespan, such as ribosomal protein knockout, calorie restriction or mTOR inhibition.

QUANTIFYING LIFE STYLE IMPACT ON LIFESPAN

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Antonello Lorenzini

2012-12-01

Full Text Available A healthy diet, physical activity and avoiding dangerous habits such as smoking are effective ways of increasing health and lifespan. Although a significant portion of the world's population still suffers from malnutrition, especially children, the most common cause of death in the world today is non-communicable diseases. Overweight and obesity significantly increase the relative risk for the most relevant non communicable diseases: cardiovascular disease, type II diabetes and some cancers. Childhood overweight also seems to increase the likelihood of disease in adulthood through epigenetic mechanisms. This worrisome trend now termed "globesity" will deeply impact society unless preventive strategies are put into effect. Researchers of the basic biology of aging have clearly established that animals with short lifespans live longer when their diet is calorie restricted. Although similar experiments carried on rhesus monkeys, a longer-lived species more closely related to humans, yielded mixed results, overall the available scientific data suggest keeping the body mass index in the "normal" range increases the chances of living a longer, healthier life. This can be successfully achieved both by maintaining a healthy diet and by engaging in physical activity. In this review we will try to quantify the relative impact of life style choices on lifespan.

The role of MAP4K3 in lifespan regulation of Caenorhabditiselegans

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Khan, Maruf H.; Hart, Matthew J.; Rea, Shane L.

2012-01-01

Highlights: ► Inhibition of MAP4K3 by RNAi leads to increased mean lifespan in Caenorhabditis elegans. ► Mutation in the citron homology domain of MAP4K3 leads to increased mean lifespan. ► Mutation in the kinase domain of MAP4K3 has no significant effect on mean lifespan. -- Abstract: The TOR pathway is a kinase signaling pathway that regulates cellular growth and proliferation in response to nutrients and growth factors. TOR signaling is also important in lifespan regulation – when this pathway is inhibited, either naturally, by genetic mutation, or by pharmacological means, lifespan is extended. MAP4K3 is a Ser/Thr kinase that has recently been found to be involved in TOR activation. Unexpectedly, the effect of this protein is not mediated via Rheb, the more widely known TOR activation pathway. Given the role of TOR in growth and lifespan control, we looked at how inhibiting MAP4K3 in Caenorhabditiselegans affects lifespan. We used both feeding RNAi and genetic mutants to look at the effect of MAP4K3 deficiency. Our results show a small but significant increase in mean lifespan in MAP4K3 deficient worms. MAP4K3 thus represents a new target in the TOR pathway that can be targeted for pharmacological intervention to control lifespan.

The role of MAP4K3 in lifespan regulation of Caenorhabditiselegans

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Khan, Maruf H. [Barshop Institute for Longevity and Aging Studies, Department of Physiology, University of Texas Health Science Center, San Antonio, TX 78240 (United States); Hart, Matthew J., E-mail: HartMJ@uthscsa.edu [Barshop Institute for Longevity and Aging Studies, Department of Molecular Medicine, University of Texas Health Science Center, San Antonio, TX 78240 (United States); Rea, Shane L., E-mail: reas3@uthscsa.edu [Barshop Institute for Longevity and Aging Studies, Department of Physiology, University of Texas Health Science Center, San Antonio, TX 78240 (United States)

2012-08-24

Highlights: Black-Right-Pointing-Pointer Inhibition of MAP4K3 by RNAi leads to increased mean lifespan in Caenorhabditis elegans. Black-Right-Pointing-Pointer Mutation in the citron homology domain of MAP4K3 leads to increased mean lifespan. Black-Right-Pointing-Pointer Mutation in the kinase domain of MAP4K3 has no significant effect on mean lifespan. -- Abstract: The TOR pathway is a kinase signaling pathway that regulates cellular growth and proliferation in response to nutrients and growth factors. TOR signaling is also important in lifespan regulation - when this pathway is inhibited, either naturally, by genetic mutation, or by pharmacological means, lifespan is extended. MAP4K3 is a Ser/Thr kinase that has recently been found to be involved in TOR activation. Unexpectedly, the effect of this protein is not mediated via Rheb, the more widely known TOR activation pathway. Given the role of TOR in growth and lifespan control, we looked at how inhibiting MAP4K3 in Caenorhabditiselegans affects lifespan. We used both feeding RNAi and genetic mutants to look at the effect of MAP4K3 deficiency. Our results show a small but significant increase in mean lifespan in MAP4K3 deficient worms. MAP4K3 thus represents a new target in the TOR pathway that can be targeted for pharmacological intervention to control lifespan.

Role of the GH/IGF-1 axis in lifespan and healthspan: lessons from animal models.

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Berryman, Darlene E; Christiansen, Jens Sandahl; Johannsson, Gudmundur; Thorner, Michael O; Kopchick, John J

2008-12-01

Animal models are fundamentally important in our quest to understand the genetic, epigenetic, and environmental factors that contribute to human aging. In comparison to humans, relatively short-lived mammals are useful models as they allow for rapid assessment of both genetic manipulation and environmental intervention as related to longevity. These models also allow for the study of clinically relevant pathologies as a function of aging. Data associated with more distant species offers additional insight and critical consideration of the basic physiological processes and molecular mechanisms that influence lifespan. Consistently, two interventions, caloric restriction and repression of the growth hormone (GH)/insulin-like growth factor-1/insulin axis, have been shown to increase lifespan in both invertebrates and vertebrate animal model systems. Caloric restriction (CR) is a nutrition intervention that robustly extends lifespan whether it is started early or later in life. Likewise, genes involved in the GH/IGF-1 signaling pathways can lengthen lifespan in vertebrates and invertebrates, implying evolutionary conservation of the molecular mechanisms. Specifically, insulin and insulin-like growth factor-1 (IGF-1)-like signaling and its downstream intracellular signaling molecules have been shown to be associated with lifespan in fruit flies and nematodes. More recently, mammalian models with reduced growth hormone (GH) and/or IGF-1 signaling have also been shown to have extended lifespans as compared to control siblings. Importantly, this research has also shown that these genetic alterations can keep the animals healthy and disease-free for longer periods and can alleviate specific age-related pathologies similar to what is observed for CR individuals. Thus, these mutations may not only extend lifespan but may also improve healthspan, the general health and quality of life of an organism as it ages. In this review, we will provide an overview of how the

Adipose gene expression response of lean and obese mice to short-term dietary restriction.

NARCIS (Netherlands)

Schothorst, Evert M van; Keijer, Jaap; Pennings, Jeroen L A; Opperhuizen, Antoon; Brom, Charissa E van den; Kohl, Thomas; Franssen-van Hal, Nicole L W; Hoebee, Barbara

2006-01-01

Overweight and obesity lead to higher morbidity risks, which are alleviated even by mild weight loss. To gain insight in the molecular effects of weight loss in adipose tissue, we analyzed the effects of short-term dietary restriction (DR) on mice fed a low-fat diet (lean mice) or a high-fat diet

Prolongevity effects of a botanical with oregano and cranberry extracts in Mexican fruit flies: examining interactions of diet restriction and age.

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Zou, Sige; Carey, James R; Liedo, Pablo; Ingram, Donald K; Yu, Binbing

2012-04-01

Botanicals rich with phytochemicals have numerous health benefits. Dietary restriction (DR) extends lifespan in diverse species. We previously demonstrated that an oregano-cranberry (OC) mixture can promote longevity in the Mexican Fruit fly (Mexfly, Anastrepha ludens Loew). However, little is known about the interaction between botanicals and DR, and the age-dependent effect of botanicals on lifespan and reproduction. Here we investigated these issues by feeding Mexflies a full or DR diet supplemented with or without 2% OC. Lifespan and daily egg production of individual flies were recorded. The effect of short-term OC supplementation was evaluated by implementing the supplementation at three age intervals-young, middle, and old age. We found that OC increased lifespan of Mexflies on the full or DR diet when compared to their respective controls. OC increased reproduction of females on the full diet and, to a lesser extent, on the DR diet. Short-term OC supplementation was not sufficient to extend lifespan for males at all three age intervals nor for females at young and old age intervals. However, OC supplementation at the middle age interval was sufficient to extend lifespan in females, while only OC supplementation at the young age interval increased reproduction in females. Our findings suggest that OC extends lifespan and promotes reproduction partly through DR-independent pathways, and short-term supplementation have varied impact on longevity and reproduction. This also suggests a positive interaction between non-genetic interventions in promoting longevity and provides guidance for using botanicals as aging interventions in humans.

Calorie Restriction Attenuates Terminal Differentiation of Immune Cells.

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White, Matthew J; Beaver, Charlotte M; Goodier, Martin R; Bottomley, Christian; Nielsen, Carolyn M; Wolf, Asia-Sophia F M; Boldrin, Luisa; Whitmore, Charlotte; Morgan, Jennifer; Pearce, Daniel J; Riley, Eleanor M

2016-01-01

Immune senescence is a natural consequence of aging and may contribute to frailty and loss of homeostasis in later life. Calorie restriction increases healthy life-span in C57BL/6J (but not DBA/2J) mice, but whether this is related to preservation of immune function, and how it interacts with aging, is unclear. We compared phenotypic and functional characteristics of natural killer (NK) cells and T cells, across the lifespan, of calorie-restricted (CR) and control C57BL/6 and DBA/2 mice. Calorie restriction preserves a naïve T cell phenotype and an immature NK cell phenotype as mice age. The splenic T cell populations of CR mice had higher proportions of CD11a - CD44 lo cells, lower expression of TRAIL, KLRG1, and CXCR3, and higher expression of CD127, compared to control mice. Similarly, splenic NK cells from CR mice had higher proportions of less differentiated CD11b - CD27 + cells and correspondingly lower proportions of highly differentiated CD11b + CD27 - NK cells. Within each of these subsets, cells from CR mice had higher expression of CD127, CD25, TRAIL, NKG2A/C/E, and CXCR3 and lower expression of KLRG1 and Ly49 receptors compared to controls. The effects of calorie restriction on lymphoid cell populations in lung, liver, and lymph nodes were identical to those seen in the spleen, indicating that this is a system-wide effect. The impact of calorie restriction on NK cell and T cell maturation is much more profound than the effect of aging and, indeed, calorie restriction attenuates these age-associated changes. Importantly, the effects of calorie restriction on lymphocyte maturation were more marked in C57BL/6 than in DBA/2J mice indicating that delayed lymphocyte maturation correlates with extended lifespan. These findings have implications for understanding the interaction between nutritional status, immunity, and healthy lifespan in aging populations.

Cardiometabolic and reproductive benefits of early dietary energy restriction and voluntary exercise in an obese PCOS-prone rodent model.

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Diane, Abdoulaye; Kupreeva, Maria; Borthwick, Faye; Proctor, Spencer D; Pierce, W David; Vine, Donna F

2015-09-01

Polycystic ovary syndrome (PCOS) is one of the most common endocrine-metabolic disorders in women of reproductive age characterized by ovulatory dysfunction, hyperandrogenism and cardiometabolic risk. The overweight-obese PCOS phenotype appears to have exacerbated reproductive dysfunction and cardiometabolic risk. In overweight-obese adult women with PCOS, exercise and energy restricted diets have shown limited and inconsistent effects on both cardiometabolic indices and reproductive outcomes. We hypothesized that an early lifestyle intervention involving exercise and dietary energy restriction to prevent or reduce the propensity for adiposity would modulate reproductive indices and cardiometabolic risk in an obese PCOS-prone rodent model. Weanling obese PCOS-prone and Lean-Control JCR:LA-cp rodents were given a chow diet ad libitum or an energy-restricted diet combined with or without voluntary exercise (4  h/day) for 8 weeks. Dietary energy restriction and exercise lowered total body weight gain and body fat mass by 30% compared to free-fed sedentary or exercising obese PCOS-prone animals (Pexercise intensity compared to free-feeding plus exercise conditions. Energy restriction and exercise decreased fasting plasma triglycerides and apoB48 concentrations in obese PCOS-prone animals compared to free-fed and exercise or sedentary groups. The energy restriction and exercise combination in obese PCOS-prone animals significantly increased plasma sex-hormone binding globulin, hypothalamic cocaine-and amphetamine-regulated transcript (CART) and Kisspeptin mRNA expression to levels of the Lean-Control group, and this was further associated with improvements in estrous cyclicity. The combination of exercise and dietary energy restriction when initiated in early life exerts beneficial effects on cardiometabolic and reproductive indices in an obese PCOS-prone rodent model, and this may be associated with normalization of the hypothalamic neuropeptides, Kisspeptin and CART

Effects of Dietary Sodium Restriction in Kidney Transplant Recipients Treated With Renin-Angiotensin-Aldosterone System Blockade: A Randomized Clinical Trial.

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de Vries, Laura V; Dobrowolski, Linn C; van den Bosch, Jacqueline J O N; Riphagen, Ineke J; Krediet, C T Paul; Bemelman, Frederike J; Bakker, Stephan J L; Navis, Gerjan

2016-06-01

In patients with chronic kidney disease receiving renin-angiotensin-aldosterone system (RAAS) blockade, dietary sodium restriction is an often-used treatment strategy to reduce blood pressure (BP) and albuminuria. Whether these effects extend to kidney transplant recipients is unknown. We therefore studied the effects of dietary sodium restriction on BP and urinary albumin excretion (UAE) in kidney transplant recipients receiving RAAS blockade. Two-center randomized crossover trial. Stable outpatient kidney transplant recipients with creatinine clearance > 30mL/min, BP ≥120/80mmHg, receiving stable RAAS blockade therapy. 6-week regular-sodium diet (target, 150mmol/24 h) and a 6-week low-sodium diet (target, 50mmol/24 h). Main outcome parameters were systolic and diastolic BP, UAE, and estimated glomerular filtration rate (eGFR) at the end of each diet period. Dietary adherence was assessed by 24-hour urinary sodium excretion. We randomly assigned 23 kidney transplant recipients, of whom 22 (mean age, 58±8 [SD] years; 50% men; mean eGFR, 51±21mL/min/1.73m(2)) completed the study. One patient withdrew from the study because of concerns regarding orthostatic hypotension on the low-sodium diet. Sodium excretion decreased from 164±50mmol/24 h during the regular-sodium diet to 87±55mmol/24 h during the low-sodium diet (mean difference, -77 [95% CI, -110 to -44] mmol/24 h; Padherence to sodium diet was achieved in 86% of patients. In stable kidney transplant recipients receiving RAAS blockade, dietary sodium restriction effectively reduces BP without affecting eGFR. Dietary sodium restriction is relevant to BP management in kidney transplant recipients receiving RAAS blockade. Copyright © 2016 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Socioeconomic status and risk factors for cardiovascular disease: Impact of dietary mediators.

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Psaltopoulou, Theodora; Hatzis, George; Papageorgiou, Nikolaos; Androulakis, Emmanuel; Briasoulis, Alexandros; Tousoulis, Dimitris

It is well known that cardiovascular disease is the leading cause of mortality in the western societies. A number of risk factors such as family history, diabetes, hypertension, obesity, diabetes, smoking and physical inactivity are responsible for a significant proportion of the overall cardiovascular risk. Interestingly, recent data suggest there is a gradient in the incidence, morbidity and mortality of cardiovascular disease across the spectrum of socioeconomic status, as this is defined by educational level, occupation or income. Additionally, dietary mediators seem to play significant role in the pathogenesis of cardiovascular disease, mediating some of the discrepancies in atherosclerosis among different socioeconomic layers. Therefore, in the present article, we aim to review the association between socioeconomic status and cardiovascular disease risk factors and the role of different dietary mediators. Copyright © 2017 Hellenic Society of Cardiology. Published by Elsevier B.V. All rights reserved.

Intermittent fasting dissociates beneficial effects of dietary restriction on glucose metabolism and neuronal resistance to injury from calorie intake

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Anson, R. Michael; Guo, Zhihong; de Cabo, Rafael; Iyun, Titilola; Rios, Michelle; Hagepanos, Adrienne; Ingram, Donald K.; Lane, Mark A.; Mattson, Mark P.

2003-01-01

Dietary restriction has been shown to have several health benefits including increased insulin sensitivity, stress resistance, reduced morbidity, and increased life span. The mechanism remains unknown, but the need for a long-term reduction in caloric intake to achieve these benefits has been assumed. We report that when C57BL/6 mice are maintained on an intermittent fasting (alternate-day fasting) dietary-restriction regimen their overall food intake is not decreased and their body weight is maintained. Nevertheless, intermittent fasting resulted in beneficial effects that met or exceeded those of caloric restriction including reduced serum glucose and insulin levels and increased resistance of neurons in the brain to excitotoxic stress. Intermittent fasting therefore has beneficial effects on glucose regulation and neuronal resistance to injury in these mice that are independent of caloric intake. PMID:12724520

Small nucleoli are a cellular hallmark of longevity.

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Tiku, Varnesh; Jain, Chirag; Raz, Yotam; Nakamura, Shuhei; Heestand, Bree; Liu, Wei; Späth, Martin; Suchiman, H Eka D; Müller, Roman-Ulrich; Slagboom, P Eline; Partridge, Linda; Antebi, Adam

2016-08-30

Animal lifespan is regulated by conserved metabolic signalling pathways and specific transcription factors, but whether these pathways affect common downstream mechanisms remains largely elusive. Here we show that NCL-1/TRIM2/Brat tumour suppressor extends lifespan and limits nucleolar size in the major C. elegans longevity pathways, as part of a convergent mechanism focused on the nucleolus. Long-lived animals representing distinct longevity pathways exhibit small nucleoli, and decreased expression of rRNA, ribosomal proteins, and the nucleolar protein fibrillarin, dependent on NCL-1. Knockdown of fibrillarin also reduces nucleolar size and extends lifespan. Among wildtype C. elegans, individual nucleolar size varies, but is highly predictive for longevity. Long-lived dietary restricted fruit flies and insulin-like-peptide mutants exhibit small nucleoli and fibrillarin expression, as do long-lived dietary restricted and IRS1 knockout mice. Furthermore, human muscle biopsies from individuals who underwent modest dietary restriction coupled with exercise also display small nucleoli. We suggest that small nucleoli are a cellular hallmark of longevity and metabolic health conserved across taxa.

Dietary restrictions in healing among speakers of Iquito, an endangered language of the Peruvian Amazon

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Jernigan Kevin A

2011-07-01

Full Text Available Abstract Background Ethnobotanical research was carried out with speakers of Iquito, a critically endangered Amazonian language of the Zaparoan family. The study focused on the concept of "dieting" (siyan++ni in Iquito, a practice involving prohibitions considered necessary to the healing process. These restrictions include: 1 foods and activities that can exacerbate illness, 2 environmental influences that conflict with some methods of healing (e.g. steam baths or enemas and 3 foods and activities forbidden by the spirits of certain powerful medicinal plants. The study tested the following hypotheses: H1 - Each restriction will correlate with specific elements in illness explanatory models and H2 - Illnesses whose explanatory models have personalistic elements will show a greater number and variety of restrictions than those based on naturalistic reasoning. Methods The work was carried out in 2009 and 2010 in the Alto Nanay region of Peru. In structured interviews, informants gave explanatory models for illness categories, including etiologies, pathophysiologies, treatments and dietary restrictions necessary for 49 illnesses. Seventeen botanical vouchers for species said to have powerful spirits that require diets were also collected. Results All restrictions found correspond to some aspect of illness explanatory models. Thirty-five percent match up with specific illness etiologies, 53% correspond to particular pathophysiologies, 18% correspond with overall seriousness of the illness and 18% are only found with particular forms of treatment. Diets based on personalistic reasoning have a significantly higher average number of restrictions than those based on naturalistic reasoning. Conclusions Dieting plays a central role in healing among Iquito speakers. Specific prohibitions can be explained in terms of specific aspects of illness etiologies, pathophysiologies and treatments. Although the Amazonian literature contains few studies focusing on

Mannan-binding lectin is involved in the protection against renal ischemia/ reperfusion injury by dietary restriction

NARCIS (Netherlands)

Shushimita; P. van der Pol (Pieter); R.W.F. de Bruin (Ron); J.N.M. IJzermans (Jan); C. van Kooten (Cees); F.J.M.F. Dor (Frank)

2015-01-01

textabstractPreoperative fasting and dietary restriction offer robust protection against renal ischemia/ reperfusion injury (I/RI) in mice.We recently showed that Mannan-binding lectin (MBL), the initiator of the lectin pathway of complement activation, plays a pivotal role in renal I/RI. Based on

Oleanolic acid activates daf-16 to increase lifespan in Caenorhabditis elegans

International Nuclear Information System (INIS)

Zhang, Jiaolong; Lu, Lulu; Zhou, Lijun

2015-01-01

Oleanolic acid (OA) is an active ingredient in natural plants. It has been reported to possess a variety of pharmacological activities, but very little is known about its effects of anti-aging. We investigate here whether OA has an impact on longevity in vivo, and more specifically, we have examined effects of OA on the lifespan and stress tolerance in Caenorhabditis elegans (C. elegans). Our results showed that OA could extend the lifespan, increase its stress resistance and reduce the intracellular reactive oxygen species (ROS) in wild-type worms. Moreover, we have found that OA-induced longevity may not be associated with the calorie restriction (CR) mechanism. Our mechanistic studies using daf-16 loss-of-function mutant strains (GR1307) indicated that the extension of lifespan by OA requires daf-16. In addition, OA treatment could also modulate the nuclear localization, and the quantitative real-time PCR results revealed that up-regulation of daf-16 target genes such as sod-3, hsp-16.2 and ctl-1 could prolong lifespan and increase stress response in C. elegans. This study overall uncovers the longevity effect of OA and its underpinning mechanisms. - Graphical abstract: Oleanolic acid modulates the activity of DAF-16 to promote longevity and increase stress resistance in Caenorhabditis elegans. - Highlights: • OA extends the lifespan of wild-type Caenorhabditis elegans. • OA improves the stress resistance and reduces the intracellular ROS level in C. elegans. • OA induces lifespan extension may not proceed through the CR mechanism. • OA extends the lifespan in C. elegans is modulated by daf-16.

Oleanolic acid activates daf-16 to increase lifespan in Caenorhabditis elegans

Energy Technology Data Exchange (ETDEWEB)

Zhang, Jiaolong; Lu, Lulu; Zhou, Lijun, E-mail: lijunzhou@tju.edu.cn

2015-12-25

Oleanolic acid (OA) is an active ingredient in natural plants. It has been reported to possess a variety of pharmacological activities, but very little is known about its effects of anti-aging. We investigate here whether OA has an impact on longevity in vivo, and more specifically, we have examined effects of OA on the lifespan and stress tolerance in Caenorhabditis elegans (C. elegans). Our results showed that OA could extend the lifespan, increase its stress resistance and reduce the intracellular reactive oxygen species (ROS) in wild-type worms. Moreover, we have found that OA-induced longevity may not be associated with the calorie restriction (CR) mechanism. Our mechanistic studies using daf-16 loss-of-function mutant strains (GR1307) indicated that the extension of lifespan by OA requires daf-16. In addition, OA treatment could also modulate the nuclear localization, and the quantitative real-time PCR results revealed that up-regulation of daf-16 target genes such as sod-3, hsp-16.2 and ctl-1 could prolong lifespan and increase stress response in C. elegans. This study overall uncovers the longevity effect of OA and its underpinning mechanisms. - Graphical abstract: Oleanolic acid modulates the activity of DAF-16 to promote longevity and increase stress resistance in Caenorhabditis elegans. - Highlights: • OA extends the lifespan of wild-type Caenorhabditis elegans. • OA improves the stress resistance and reduces the intracellular ROS level in C. elegans. • OA induces lifespan extension may not proceed through the CR mechanism. • OA extends the lifespan in C. elegans is modulated by daf-16.

Dietary sodium restriction in the prophylaxis of hypertensive disorders of pregnancy: effects on the intake of other nutrients.

Science.gov (United States)

van Buul, B J; Steegers, E A; Jongsma, H W; Rijpkema, A L; Eskes, T K; Thomas, C M; Baadenhuysen, H; Hein, P R

1995-07-01

Dietary sodium restriction is used in the Netherlands in the prophylaxis of preeclampsia. To study the effects of long-term sodium restriction on the intake of other nutrients and the outcome of pregnancy, 68 healthy nulliparous pregnant women were randomly assigned to either a low-sodium diet (20 mmol/24 h) or an unrestricted diet. The diet was consumed between week 14 of gestation and delivery. The dietary intakes of energy, fat, protein, carbohydrate, sodium, potassium, and calcium were estimated with the dietary-history technique. A low-sodium diet reduced the intake of protein (by approximately 15 g/24 h), fat (by 20 g/24 h), and calcium (by 350 mg/24 h) and tended to decrease the energy intake (by approximately 0.7 MJ/24 h). The intakes of carbohydrate and potassium did not differ between the groups. The maternal weight gain was less in the low-sodium group (6.0 +/- 3.7 compared with 11.7 +/- 4.7 kg). Mean birth weight was not significantly different (3.2 +/- 0.5 compared with 3.4 +/- 0.5 kg).

Combined treatment of rapamycin and dietary restriction has a larger effect on the transcriptome and metabolome of liver.

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Fok, Wilson C; Bokov, Alex; Gelfond, Jonathan; Yu, Zhen; Zhang, Yiqiang; Doderer, Mark; Chen, Yidong; Javors, Martin; Wood, William H; Zhang, Yongqing; Becker, Kevin G; Richardson, Arlan; Pérez, Viviana I

2014-04-01

Rapamycin (Rapa) and dietary restriction (DR) have consistently been shown to increase lifespan. To investigate whether Rapa and DR affect similar pathways in mice, we compared the effects of feeding mice ad libitum (AL), Rapa, DR, or a combination of Rapa and DR (Rapa + DR) on the transcriptome and metabolome of the liver. The principal component analysis shows that Rapa and DR are distinct groups. Over 2500 genes are significantly changed with either Rapa or DR when compared with mice fed AL; more than 80% are unique to DR or Rapa. A similar observation was made when genes were grouped into pathways; two-thirds of the pathways were uniquely changed by DR or Rapa. The metabolome shows an even greater difference between Rapa and DR; no metabolites in Rapa-treated mice were changed significantly from AL mice, whereas 173 metabolites were changed in the DR mice. Interestingly, the number of genes significantly changed by Rapa + DR when compared with AL is twice as large as the number of genes significantly altered by either DR or Rapa alone. In summary, the global effects of DR or Rapa on the liver are quite different and a combination of Rapa and DR results in alterations in a large number of genes and metabolites that are not significantly changed by either manipulation alone, suggesting that a combination of DR and Rapa would be more effective in extending longevity than either treatment alone. © 2013 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

Dietary sodium restriction reverses vascular endothelial dysfunction in middle-aged/older adults with moderately elevated systolic blood pressure

Science.gov (United States)

Jablonski, Kristen L.; Racine, Matthew L.; Geolfos, Candace J.; Gates, Phillip E.; Chonchol, Michel; McQueen, Matthew B.; Seals, Douglas R.

2013-01-01

Objectives We determined the efficacy of dietary sodium restriction (DSR) for improving vascular endothelial dysfunction in middle-aged/older adults with moderately elevated systolic blood pressure (SBP; 130–159 mmHg) and the associated physiological mechanisms. Background Vascular endothelial dysfunction develops with advancing age and elevated SBP, contributing to increased cardiovascular risk. DSR lowers BP, but its effect on vascular endothelial function and mechanisms involved are unknown. Methods Seventeen subjects (11M/6F; 62±7 yrs, mean±S.D.) completed a randomized, crossover study of 4 weeks of both low and normal sodium intake. Vascular endothelial function (endothelium-dependent dilation; EDD), nitric oxide (NO)/tetrahydrobiopterin (BH4) bioavailability and oxidative stress-associated mechanisms were assessed following each condition. Results Urinary sodium excretion was reduced by ~50% (to 70±30 mmol/day), and conduit (brachial artery flow-mediated dilation [FMDBA]) and resistance (forearm blood flow responses to acetylcholine [FBFACh]) artery EDD were 68% and 42% (peak FBFACh) higher following the low sodium diet (psodium markedly enhanced NO- mediated EDD (greater ΔFBFACh with endothelial NO synthase [eNOS] inhibition) without changing eNOS expression/activation (Ser1177 phosphorylation), restored BH4 bioactivity (less ΔFMDBA with acute BH4), abolished tonic superoxide suppression of EDD (less ΔFMDBA and ΔFBFACh with ascorbic acid infusion), and increased circulating superoxide dismutase activity (p<0.05). These effects were independent of ΔSBP. Other subject characteristics/dietary factors and endothelium-independent dilation were unchanged. Conclusions DSR largely reverses both macro- and microvascular endothelial dysfunction by enhancing NO and BH4 bioavailability and reducing oxidative stress. Our findings support the emerging concept that DSR induces “vascular protection” beyond that attributable to its BP-lowering effects. PMID

Temporary dietary iron restriction affects the process of thrombus resolution in a rat model of deep vein thrombosis.

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Makiko Oboshi

Full Text Available Deep vein thrombosis (DVT is a major cause of pulmonary thromboembolism and sudden death. Thus, it is important to consider the pathophysiology of DVT. Recently, iron has been reported to be associated with thrombotic diseases. Hence, in this study, we investigate the effects of dietary iron restriction on the process of thrombus resolution in a rat model of DVT.We induced DVT in 8-week-old male Sprague-Dawley rats by performing ligations of their inferior venae cavae. The rats were then given either a normal diet (DVT group or an iron-restricted diet (DVT+IR group. Thrombosed inferior venae cavae were harvested at 5 days after ligation.The iron-restricted diet reduced venous thrombus size compared to the normal diet. Intrathrombotic collagen content was diminished in the DVT+IR group compared to the DVT group. In addition, intrathrombotic gene expression and the activity of matrix metalloproteinase-9 were increased in the DVT+IR group compared to the DVT group. Furthermore, the DVT+IR group had greater intrathrombotic neovascularization as well as higher gene expression levels of urokinase-type plasminogen activator and tissue-type plasminogen activator than the DVT group. The iron-restricted diet decreased intrathrombotic superoxide production compared to the normal diet.These results suggest that dietary iron restriction affects the process of thrombus resolution in DVT.

Temporary dietary iron restriction affects the process of thrombus resolution in a rat model of deep vein thrombosis.

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Oboshi, Makiko; Naito, Yoshiro; Sawada, Hisashi; Hirotani, Shinichi; Iwasaku, Toshihiro; Okuhara, Yoshitaka; Morisawa, Daisuke; Eguchi, Akiyo; Nishimura, Koichi; Fujii, Kenichi; Mano, Toshiaki; Ishihara, Masaharu; Masuyama, Tohru

2015-01-01

Deep vein thrombosis (DVT) is a major cause of pulmonary thromboembolism and sudden death. Thus, it is important to consider the pathophysiology of DVT. Recently, iron has been reported to be associated with thrombotic diseases. Hence, in this study, we investigate the effects of dietary iron restriction on the process of thrombus resolution in a rat model of DVT. We induced DVT in 8-week-old male Sprague-Dawley rats by performing ligations of their inferior venae cavae. The rats were then given either a normal diet (DVT group) or an iron-restricted diet (DVT+IR group). Thrombosed inferior venae cavae were harvested at 5 days after ligation. The iron-restricted diet reduced venous thrombus size compared to the normal diet. Intrathrombotic collagen content was diminished in the DVT+IR group compared to the DVT group. In addition, intrathrombotic gene expression and the activity of matrix metalloproteinase-9 were increased in the DVT+IR group compared to the DVT group. Furthermore, the DVT+IR group had greater intrathrombotic neovascularization as well as higher gene expression levels of urokinase-type plasminogen activator and tissue-type plasminogen activator than the DVT group. The iron-restricted diet decreased intrathrombotic superoxide production compared to the normal diet. These results suggest that dietary iron restriction affects the process of thrombus resolution in DVT.

Testing the Effects of DL-Alpha-Tocopherol Supplementation on Oxidative Damage, Total Antioxidant Protection and the Sex-Specific Responses of Reproductive Effort and Lifespan to Dietary Manipulation in Australian Field Crickets (Teleogryllus commodus

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C. Ruth Archer

2015-12-01

Full Text Available The oxidative stress theory predicts that the accumulation of oxidative damage causes aging. More generally, oxidative damage could be a cost of reproduction that reduces survival. Both of these hypotheses have mixed empirical support. To better understand the life-history consequences of oxidative damage, we fed male and female Australian field crickets (Teleogryllus commodus four diets differing in their protein and carbohydrate content, which have sex-specific effects on reproductive effort and lifespan. We supplemented half of these crickets with the vitamin E isoform DL-alpha-tocopherol and measured the effects of nutrient intake on lifespan, reproduction, oxidative damage and antioxidant protection. We found a clear trade-off between reproductive effort and lifespan in females but not in males. In direct contrast to the oxidative stress theory, crickets fed diets that improved their lifespan had high levels of oxidative damage to proteins. Supplementation with DL-alpha-tocopherol did not significantly improve lifespan or reproductive effort. However, males fed diets that increased their reproductive investment experienced high oxidative damage to proteins. While this suggests that male reproductive effort could elevate oxidative damage, this was not associated with reduced male survival. Overall, these results provide little evidence that oxidative damage plays a central role in mediating life-history trade-offs in T. commodus.

Toxicokinetics of chloral hydrate in ad libitum-fed, dietary-controlled, and calorically restricted male B6C3F1 mice following short-term exposure

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Seng, John E.; Agrawal, Nalini; Horsley, Elizabeth T.M.; Leakey, Tatiana I.; Scherer, Erin M.; Xia, Shijun; Allaben, William T.; Leakey, Julian E.A.

2003-01-01

Chloral hydrate is widely used as a sedative in pediatric medicine and is a by-product of water chlorination and a metabolic intermediate in the biotransformation of trichloroethylene. Chloral hydrate and its major metabolite, trichloroacetic acid, induce liver tumors in B6C3F 1 mice, a strain that can exhibit high rates of background liver tumor incidence, which is associated with increased body weight. This report describes the influence of diet and body weight on the acute toxicity, hepatic enzyme response, and toxickinetics of chloral hydrate as part of a larger study investigating the carcinogenicity of chloral hydrate in ad libitum-fed and dietary controlled mice. Dietary control involves moderate food restriction to maintain the test animals at an idealized body weight. Mice were dosed with chloral hydrate at 0, 50, 100, 250, 500, and 1000 mg/kg daily, 5 days/week, by aqueous gavage for 2 weekly dosing cycles. Three diet groups were used: ad libitum, dietary control, and 40% caloric restriction. Both dietary control and caloric restriction slightly reduced acute toxicity of high doses of chloral hydrate and potentiated the induction of hepatic enzymes associated with peroxisome proliferation. Chloral hydrate toxicokinetics were investigated using blood samples obtained by sequential tail clipping and a microscale gas chromatography technique. It was rapidly cleared from serum within 3 h of dosing. Trichloroacetate was the major metabolite in serum in all three diet groups. Although the area under the curve values for serum trichloroacetate were slightly greater in the dietary controlled and calorically restricted groups than in the ad libitum-fed groups, this increase did not appear to completely account for the potentiation of hepatic enzyme induction by dietary restriction

Reduced costs of reproduction in females mediate a shift from a male-biased to a female-biased lifespan in humans

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Bolund, Elisabeth; Lummaa, Virpi; Smith, Ken R.; Hanson, Heidi A.; Maklakov, Alexei A.

2016-01-01

The causes underlying sex differences in lifespan are strongly debated. While females commonly outlive males in humans, this is generally less pronounced in societies before the demographic transition to low mortality and fertility rates. Life-history theory suggests that reduced reproduction should benefit female lifespan when females pay higher costs of reproduction than males. Using unique longitudinal demographic records on 140,600 reproducing individuals from the Utah Population Database, we demonstrate a shift from male-biased to female-biased adult lifespans in individuals born before versus during the demographic transition. Only women paid a cost of reproduction in terms of shortened post-reproductive lifespan at high parities. Therefore, as fertility decreased over time, female lifespan increased, while male lifespan remained largely stable, supporting the theory that differential costs of reproduction in the two sexes result in the shifting patterns of sex differences in lifespan across human populations. Further, our results have important implications for demographic forecasts in human populations and advance our understanding of lifespan evolution. PMID:27087670

Natural thioallyl compounds increase oxidative stress resistance and lifespan in Caenorhabditis elegans by modulating SKN-1/Nrf.

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Ogawa, Takahiro; Kodera, Yukihiro; Hirata, Dai; Blackwell, T Keith; Mizunuma, Masaki

2016-02-22

Identification of biologically active natural compounds that promote health and longevity, and understanding how they act, will provide insights into aging and metabolism, and strategies for developing agents that prevent chronic disease. The garlic-derived thioallyl compounds S-allylcysteine (SAC) and S-allylmercaptocysteine (SAMC) have been shown to have multiple biological activities. Here we show that SAC and SAMC increase lifespan and stress resistance in Caenorhabditis elegans and reduce accumulation of reactive oxygen species (ROS). These compounds do not appear to activate DAF-16 (FOXO orthologue) or mimic dietary restriction (DR) effects, but selectively induce SKN-1 (Nrf1/2/3 orthologue) targets involved in oxidative stress defense. Interestingly, their treatments do not facilitate SKN-1 nuclear accumulation, but slightly increased intracellular SKN-1 levels. Our data also indicate that thioallyl structure and the number of sulfur atoms are important for SKN-1 target induction. Our results indicate that SAC and SAMC may serve as potential agents that slow aging.

Active Hexose Correlated Compound Extends the Lifespan and Increases the Thermotolerance of Nematodes

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Tetsuya Okuyama

2013-06-01

Full Text Available ABSTRACTBackground: Active hexose correlated compound (AHCC is the extract from cultured mycelia of Lentinula edodes, a species of Basidiomycetes mushroom. AHCC contains various polysaccharides, including partially acylated -1,4-glucan, which is one of its major constituents. The application of AHCC has been markedly increased in complementary and alternative medicine as a functional food because AHCC improved the prognosis of postoperative hepatocellular carcinoma patients. AHCC has anti-inflammatory and antioxidant effects, such as the suppression of nitric oxide production in hepatocytes. AHCC might affect resistance to environmental stress, which is assumed to play a pivotal role in the longevity of many organisms.Objective: To investigate the effect of AHCC on longevity, we measured the lifespan of the nematode Caenorhabditis elegans, a model animal that is widely used to assess longevity. We also examined the effect of AHCC on resistance to heat stress, i.e., thermotolerance.Methods: The lifespan of C. elegans animals grown on media in the absence or presence of AHCC at 20°C was evaluated. Thermotolerance assays were performed at 35°C, the restrictive temperature of the animals. The effects of AHCC on lifespan and thermotolerance were analyzed with longevity mutants. Expression levels of stress-related genes, including heat shock genes, were measured by strand-specific reverse transcription-polymerase chain reaction after heat shock.Results: Wild-type C. elegans animals exhibited a longer mean lifespan by up to 10% in the presence of AHCC in the growth media than animals in the absence of AHCC. Furthermore, AHCC markedly increased thermotolerance at 35°C. Epistasis analyses showed that lifespan extension by AHCC at least partly required two longevity-promoting transcription factors: DAF-16 (C. elegans homolog of FOXO and HSF-1 (C. elegans homolog of heat shock transcription factor 1. After heat shock, AHCC activated the transcription

Dietary and fluid restrictions in CKD: a thematic synthesis of patient views from qualitative studies.

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Palmer, Suetonia C; Hanson, Camilla S; Craig, Jonathan C; Strippoli, Giovanni F M; Ruospo, Marinella; Campbell, Katrina; Johnson, David W; Tong, Allison

2015-04-01

Managing the complex fluid and diet requirements of chronic kidney disease (CKD) is challenging for patients. We aimed to summarize patients' perspectives of dietary and fluid management in CKD to inform clinical practice and research. Systematic review of qualitative studies. Adults with CKD who express opinions about dietary and fluid management. MEDLINE, EMBASE, PsycINFO, CINAHL, Google Scholar, reference lists, and PhD dissertations were searched to May 2013. Thematic synthesis. We included 46 studies involving 816 patients living in middle- to high-income countries. Studies involved patients treated with facility-based and home hemodialysis (33 studies; 462 patients), peritoneal dialysis (10 studies; 112 patients), either hemodialysis or peritoneal dialysis (3 studies; 73 patients), kidney transplant recipients (9 studies; 89 patients), and patients with non-dialysis-dependent CKD stages 1 to 5 (5 studies; 80 patients). Five major themes were identified: preserving relationships (interference with roles, social limitations, and being a burden), navigating change (feeling deprived, disrupting held truths, breaking habits and norms, being overwhelmed by information, questioning efficacy, and negotiating priorities), fighting temptation (resisting impositions, experiencing mental invasion, and withstanding physiologic needs), optimizing health (accepting responsibility, valuing self-management, preventing disease progression, and preparing for and protecting a transplant), and becoming empowered (comprehending paradoxes, finding solutions, and mastering change and demands). Limited data in non-English languages and low-income settings and for adults with CKD not treated with hemodialysis. Dietary and fluid restrictions are disorienting and an intense burden for patients with CKD. Patient-prioritized education strategies, harnessing patients' motivation to stay well for a transplant or to avoid dialysis, and viewing adaptation to restrictions as a collaborative

Impact of caloric and dietary restriction regimens on markers of health and longevity in humans and animals: a summary of available findings

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Trepanowski, John F; Canale, Robert E; Marshall, Kate E; Kabir, Mohammad M; Bloomer, Richard J

2011-01-01

Abstract Considerable interest has been shown in the ability of caloric restriction (CR) to improve multiple parameters of health and to extend lifespan. CR is the reduction of caloric intake - typically by 20 - 40% of ad libitum consumption - while maintaining adequate nutrient intake. Several alternatives to CR exist. CR combined with exercise (CE) consists of both decreased caloric intake and increased caloric expenditure. Alternate-day fasting (ADF) consists of two interchanging days; one...

The Yang-Tonifying Herbal Medicine Cynomorium songaricum Extends Lifespan and Delays Aging in Drosophila

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Hsin-Ping Liu

2012-01-01

Full Text Available Aging is highly correlated with the progressive loss of physiological function, including cognitive behavior and reproductive capacity, as well as an increased susceptibility to diseases; therefore, slowing age-related degeneration could greatly contribute to human health. Cynomorium songaricum Rupr. (CS is traditionally used to improve sexual function and treat kidney dysfunction in traditional Chinese medicine, although little is known about whether CS has effects on longevity. Here, we show that CS supplementation in the diet extends both the mean and maximum lifespan of adult female flies. The increase in lifespan with CS was correlated with higher resistance to oxidative stress and starvation and lower lipid hydroperoxides (LPO levels. Additionally, the lifespan extension was accompanied by beneficial effects, such as improved mating readiness, increased fecundity, and suppression of age-related learning impairment in aged flies. These findings demonstrate the important antiaging effects of CS and indicate the potential applicability of dietary intervention with CS to enhance health and prevent multiple age-related diseases.

Epigenetic Effects of Diet on Fruit Fly Lifespan: An Investigation to Teach Epigenetics to Biology Students

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Billingsley, James; Carlson, Kimberly A.

2010-01-01

Do our genes exclusively control us, or are other factors at play? Epigenetics can provide a means for students to use inquiry-based methods to understand a complex biological concept. Students research and design an experiment testing whether dietary supplements affect the lifespan of Drosophila melanogaster over multiple generations.

Mitochondrial Respiratory Thresholds Regulate Yeast Chronological Lifespan and its Extension by Caloric Restriction

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Ocampo, Alejandro; Liu, Jingjing; Schroeder, Elizabeth A.; Shadel, Gerald S.; Barrientos, Antoni

2012-01-01

We have explored the role of mitochondrial function in aging by genetically and pharmacologically modifying yeast cellular respiration production during the exponential and/or stationary growth phases, and determining how this affects chronological lifespan (CLS). Our results demonstrate that respiration is essential during both growth phases for standard CLS, but that yeast have a large respiratory capacity and only deficiencies below a threshold (~40% of wild-type) significantly curtail CLS...

Oleanolic acid activates daf-16 to increase lifespan in Caenorhabditis elegans.

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Zhang, Jiaolong; Lu, Lulu; Zhou, Lijun

2015-12-25

Oleanolic acid (OA) is an active ingredient in natural plants. It has been reported to possess a variety of pharmacological activities, but very little is known about its effects of anti-aging. We investigate here whether OA has an impact on longevity in vivo, and more specifically, we have examined effects of OA on the lifespan and stress tolerance in Caenorhabditis elegans (C. elegans). Our results showed that OA could extend the lifespan, increase its stress resistance and reduce the intracellular reactive oxygen species (ROS) in wild-type worms. Moreover, we have found that OA-induced longevity may not be associated with the calorie restriction (CR) mechanism. Our mechanistic studies using daf-16 loss-of-function mutant strains (GR1307) indicated that the extension of lifespan by OA requires daf-16. In addition, OA treatment could also modulate the nuclear localization, and the quantitative real-time PCR results revealed that up-regulation of daf-16 target genes such as sod-3, hsp-16.2 and ctl-1 could prolong lifespan and increase stress response in C. elegans. This study overall uncovers the longevity effect of OA and its underpinning mechanisms. Copyright © 2015 Elsevier Inc. All rights reserved.

Dietary Sodium Restriction and Association with Urinary Marinobufagenin, Blood Pressure, and Aortic Stiffness

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Fedorova, Olga V.; Racine, Matthew L.; Geolfos, Candace J.; Gates, Phillip E.; Chonchol, Michel; Fleenor, Bradley S.; Lakatta, Edward G.; Bagrov, Alexei Y.; Seals, Douglas R.

2013-01-01

Summary Background and objectives Systolic BP and large elastic artery stiffness both increase with age and are reduced by dietary sodium restriction. Production of the natriuretic hormone marinobufagenin, an endogenous α1 Na+,K+-ATPase inhibitor, is increased in salt-sensitive hypertension and contributes to the rise in systolic BP during sodium loading. Design, setting, participants, & measurements The hypothesis was that dietary sodium restriction performed in middle-aged/older adults (eight men and three women; 60±2 years) with moderately elevated systolic BP (139±2/83±2 mmHg) would reduce urinary marinobufagenin excretion as well as systolic BP and aortic pulse-wave velocity (randomized, placebo-controlled, and crossover design). This study also explored the associations among marinobufagenin excretion with systolic BP and aortic pulse-wave velocity across conditions of 5 weeks of a low-sodium (77±9 mmol/d) and 5 weeks of a normal-sodium (144±7 mmol/d) diet. Results Urinary marinobufagenin excretion (weekly measurements; 25.4±1.8 versus 30.7±2.1 pmol/kg per day), systolic BP (127±3 versus 138±5 mmHg), and aortic pulse-wave velocity (700±40 versus 843±36 cm/s) were lower during the low- versus normal-sodium condition (all Psodium excretion (slope=0.46, Psodium condition (both Psodium restriction reduces urinary marinobufagenin excretion and that urinary marinobufagenin excretion is positively associated with systolic BP, aortic stiffness (aortic pulse-wave velocity), and endothelial cell expression of the oxidant enzyme NAD(P)H oxidase. Importantly, marinobufagenin excretion is positively related to systolic BP over ranges of sodium intake typical of an American diet, extending previous observations in rodents and humans fed experimentally high-sodium diets. PMID:23929930

Long-term dietary restriction up-regulates activity and expression of renal arginase II in aging mice.

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Majaw, T; Sharma, R

2017-06-01

Arginase II is a mitochondrial enzyme that catalyses the hydrolysis of L-arginine into urea and ornithine. It is present in other extra-hepatic tissues that lack urea cycle. Therefore, it is plausible that arginase II has a physiological role other than urea cycle which includes polyamine, proline, glutamate synthesis and regulation of nitric oxide production. The high expression of arginase II in kidney, among extrahepatic tissues, might have an important role associated with kidney functions. The present study is aimed to determine the age-associated alteration in the activity and expression of arginase II in the kidney of mice of different ages. The effect of dietary restriction to modulate the agedependent changes of arginase II was also studied. Results showed that renal arginase II activity declines significantly with the progression of age (p less than 0.01 and p less than 0.001 in 6- and 18-month-old mice, respectively as compared to 2-month old mice) and is due to the reduction in its protein as well as the mRNA level (p less than 0.001 in both 6- and 18-month-old mice as compared to 2-month-old mice). Long-term dietary restriction for three months has significantly up-regulated arginase II activity and expression level in both 2- and 18-month-old mice (p less than 0.01 and p less than 0.001, respectively as compared to AL group). These findings clearly indicate that the reducing level of arginase II during aging might have an impact on the declining renal functions. This age-dependent down-regulation of arginase II in the kidney can be attenuated by dietary restriction which may help in the maintenance of such functions.

Testing theories of dietary behavior change in youth using the mediating variable model with intervention programs

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Our purpose was to review and critique current experimentally based evidence of theoretical mechanisms of dietary behavior change in youth, and provide recommendations on ways to enhance theory evaluation. Interventions that examined mediators of dietary behavior change in youth (age 5-18 years) wer...

Adherence to dietary recommendations in diabetes mellitus: disease acceptance as a potential mediator.

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Jaworski, Mariusz; Panczyk, Mariusz; Cedro, Małgorzata; Kucharska, Alicja

2018-01-01

Adherence by diabetic patients to dietary recommendations is important for effective therapy. Considering patients' expectations in case of diet is significant in this regard. The aim of this paper was to analyze the relationship between selected independent variables (eg, regular blood glucose testing) and patients' adherence to dietary recommendations, bearing in mind that the degree of disease acceptance might play a mediation role. A cross-sectional study was conducted in 91 patients treated for type 2 diabetes mellitus in a public medical facility. Paper-and-pencil interviewing was administered ahead of the planned visit with a diabetes specialist. Two measures were applied in the study: the Acceptance and Action Diabetes Questionnaire and the Patient Diet Adherence in Diabetes Scale. Additionally, data related to sociodemographic characteristics, lifestyle-related factors, and the course of the disease (management, incidence of complications, and dietician's supervision) were also collected. The regression method was used in the analysis, and Cohen's methodology was used to estimate partial mediation. Significance of the mediation effect was assessed by the Goodman test. P -values of diet and concomitant oral medicines and/or insulin therapy. Effective dietary education should include activities promoting a more positive attitude toward the disease. This may be obtained by individual counseling, respecting the patient's needs, and focus on regular blood glucose testing.

Prolonged calorie restriction downregulates skeletal muscle mTORC1 signaling independent of dietary protein intake and associated microRNA expression

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Lee M Margolis

2016-10-01

Full Text Available Short-term (5-10 days calorie restriction (CR downregulates muscle protein synthesis, with consumption of a high protein-based diet attenuating this decline. Benefit of increase protein intake is believed to be due to maintenance of amino acid-mediated anabolic signaling through the mechanistic target of rapamycin complex 1 (mTORC1, however, there is limited evidence to support this contention. The purpose of this investigation was to determine the effects of prolonged CR and high protein diets on skeletal muscle mTORC1 signaling and expression of associated microRNA (miR. 12-wk old male Sprague Dawley rats consumed ad libitum (AL or calorie restricted (CR; 40% adequate (10%, AIN-93M or high (32% protein milk-based diets for 16 weeks. Body composition was determined using dual energy X-ray absorptiometry and muscle protein content was calculated from muscle homogenate protein concentrations expressed relative to fat-free mass to estimate protein content. Western blot and RT-qPCR were used to determine mTORC1 signaling and mRNA and miR expression in fasted mixed gastrocnemius. Independent of dietary protein intake, muscle protein content was 38% lower (P < 0.05 in CR compared to AL. Phosphorylation and total Akt, mTOR, rpS6 and p70S6K were lower (P < 0.05 in CR versus AL, and total rpS6 was associated with muscle protein content (r = 0.64, r2 = 0.36. Skeletal muscle miR expression was not altered by either energy or protein intake. This study provides evidence that chronic CR attenuates muscle protein content by downregulating mTORC1 signaling. This response is independent of skeletal muscle miR and dietary protein.

Resistance to oxidative stress induced by paraquat correlates well with both decreased and increased lifespan in Drosophila melanogaster

NARCIS (Netherlands)

Vermeulen, CJ; Van De Zande, L; Bijlsma, R

2005-01-01

There is increasing support for the notion that genetic variation for lifespan, both within and between species, is correlated with variation in the efficiency of the free radical scavenging system and the ability to withstand oxidative stress. In Drosophila, resistance to dietary paraquat, a free

Testing Theories of Dietary Behavior Change in Youth Using the Mediating Variable Model with Intervention Programs

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Cerin, Ester; Barnett, Anthony; Baranowski, Tom

2009-01-01

Objective: To review and critique current experimentally-based evidence of theoretical mechanisms of dietary behavior change in youth and provide recommendations on ways to enhance theory evaluation. Methods: Interventions that examined mediators of dietary behavior change in youth (age 5-18 years) were identified via electronic database searches…

Short-term weight loss and hepatic triglyceride reduction: evidence of a metabolic advantage with dietary carbohydrate restriction123

OpenAIRE

Browning, Jeffrey D; Baker, Jonathan A; Rogers, Thomas; Davis, Jeannie; Satapati, Santhosh; Burgess, Shawn C

2011-01-01

Background: Individuals with nonalcoholic fatty liver disease (NAFLD) have excess intrahepatic triglycerides. This is due, in part, to increased hepatic synthesis of fat from carbohydrates via lipogenesis. Although weight loss is currently recommended to treat NAFLD, little attention has been given to dietary carbohydrate restriction.

Calorie restriction in rodents: Caveats to consider.

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Ingram, Donald K; de Cabo, Rafael

2017-10-01

The calorie restriction paradigm has provided one of the most widely used and most useful tools for investigating mechanisms of aging and longevity. By far, rodent models have been employed most often in these endeavors. Over decades of investigation, claims have been made that the paradigm produces the most robust demonstration that aging is malleable. In the current review of the rodent literature, we present arguments that question the robustness of the paradigm to increase lifespan and healthspan. Specifically, there are several questions to consider as follows: (1) At what age does CR no longer produce benefits? (2) Does CR attenuate cognitive decline? (3) Are there negative effects of CR, including effects on bone health, wound healing, and response to infection? (4) How important is schedule of feeding? (5) How long does CR need to be imposed to be effective? (6) How do genotype and gender influence CR? (7) What role does dietary composition play? Consideration of these questions produce many caveats that should guide future investigations to move the field forward. Published by Elsevier B.V.

Extension of lifespan in C. elegans by naphthoquinones that act through stress hormesis mechanisms.

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Piper R Hunt

Full Text Available Hormesis occurs when a low level stress elicits adaptive beneficial responses that protect against subsequent exposure to severe stress. Recent findings suggest that mild oxidative and thermal stress can extend lifespan by hormetic mechanisms. Here we show that the botanical pesticide plumbagin, while toxic to C. elegans nematodes at high doses, extends lifespan at low doses. Because plumbagin is a naphthoquinone that can generate free radicals in vivo, we investigated whether it extends lifespan by activating an adaptive cellular stress response pathway. The C. elegans cap'n'collar (CNC transcription factor, SKN-1, mediates protective responses to oxidative stress. Genetic analysis showed that skn-1 activity is required for lifespan extension by low-dose plumbagin in C. elegans. Further screening of a series of plumbagin analogs identified three additional naphthoquinones that could induce SKN-1 targets in C. elegans. Naphthazarin showed skn-1dependent lifespan extension, over an extended dose range compared to plumbagin, while the other naphthoquinones, oxoline and menadione, had differing effects on C. elegans survival and failed to activate ARE reporter expression in cultured mammalian cells. Our findings reveal the potential for low doses of naturally occurring naphthoquinones to extend lifespan by engaging a specific adaptive cellular stress response pathway.

Adherence to dietary recommendations in diabetes mellitus: disease acceptance as a potential mediator

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Jaworski M

2018-01-01

Full Text Available Mariusz Jaworski,1 Mariusz Panczyk,1 Małgorzata Cedro,2 Alicja Kucharska3 1Division of Teaching and Outcomes of Education, Faculty of Health Sciences, Medical University of Warsaw, Warsaw, Poland; 2Faculty of Health Sciences, Medical University of Warsaw, Warsaw, Poland; 3Department of Human Nutrition, Faculty of Health Sciences, Medical University of Warsaw, Warsaw, Poland Background: Adherence by diabetic patients to dietary recommendations is important for effective therapy. Considering patients’ expectations in case of diet is significant in this regard. The aim of this paper was to analyze the relationship between selected independent variables (eg, regular blood glucose testing and patients’ adherence to dietary recommendations, bearing in mind that the degree of disease acceptance might play a mediation role.Subjects and methods: A cross-sectional study was conducted in 91 patients treated for type 2 diabetes mellitus in a public medical facility. Paper-and-pencil interviewing was administered ahead of the planned visit with a diabetes specialist. Two measures were applied in the study: the Acceptance and Action Diabetes Questionnaire and the Patient Diet Adherence in Diabetes Scale. Additionally, data related to sociodemographic characteristics, lifestyle-related factors, and the course of the disease (management, incidence of complications, and dietician’s supervision were also collected. The regression method was used in the analysis, and Cohen’s methodology was used to estimate partial mediation. Significance of the mediation effect was assessed by the Goodman test. P-values of <0.05 were considered statistically significant.Results: Patients’ non-adherence to dietary recommendations was related to a low level of disease acceptance (standardized regression coefficient =−0.266; P=0.010. Moreover, failure to perform regular blood glucose testing was associated with a lack of disease acceptance (standardized regression

Restriction on an energy-dense diet improves markers of metabolic health and cellular aging in mice through decreasing hepatic mTOR activity.

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Schloesser, Anke; Campbell, Graeme; Glüer, Claus-Christian; Rimbach, Gerald; Huebbe, Patricia

2015-02-01

Dietary restriction (DR) on a normal low-fat diet improves metabolic health and may prolong life span. However, it is still uncertain whether restriction of an energy-dense, high-fat diet would also be beneficial and mitigate age-related processes. In the present study, we determined biomarkers of metabolic health, energy metabolism, and cellular aging in obesity-prone mice subjected to 30% DR on a high-fat diet for 6 months. Dietary-restricted mice had significantly lower body weights, less adipose tissue, lower energy expenditure, and altered substrate oxidation compared to their ad libitum-fed counterparts. Hepatic major urinary proteins (Mup) expression, which is linked to glucose and energy metabolism, and biomarkers of metabolic health, including insulin, glucose, cholesterol, and leptin/adiponectin ratio, were likewise reduced in high-fat, dietary-restricted mice. Hallmarks of cellular senescence such as Lamp2a and Hsc70 that mediate chaperone-mediated autophagy were induced and mechanistic target of rapamycin (mTOR) signaling mitigated upon high-fat DR. In contrast to DR applied in low-fat diets, anti-oxidant gene expression, proteasome activity, as well as 5'-adenosine monophosphate-activated protein kinase (AMPK) activation were not changed, suggesting that high-fat DR may attenuate some processes associated with cellular aging without the induction of cellular stress response or energy deprivation.

Diet-related restrictive parenting practices. Impact on dietary intake of 2-year-old children and interactions with child characteristics

NARCIS (Netherlands)

Gubbels, J.S.; Kremers, S.P.J.; Stafleu, A.; Dagnelie, P.C.; Goldbohm, R.A.; Vries, N.K.de; Thijs, C.

2009-01-01

This study examined the relationship between diet-related parenting practices, parental characteristics, child characteristics, and 2-year-old child's dietary intake. Cross-sectional data (N = 2578) originated from the KOALA Birth Cohort Study. Principal component analyses revealed two restrictive

Induction of cytoprotective pathways is central to the extension of lifespan conferred by multiple longevity pathways.

Directory of Open Access Journals (Sweden)

David E Shore

Full Text Available Many genetic and physiological treatments that extend lifespan also confer resistance to a variety of stressors, suggesting that cytoprotective mechanisms underpin the regulation of longevity. It has not been established, however, whether the induction of cytoprotective pathways is essential for lifespan extension or merely correlated. Using a panel of GFP-fused stress response genes, we identified the suites of cytoprotective pathways upregulated by 160 gene inactivations known to increase Caenorhabditis elegans longevity, including the mitochondrial UPR (hsp-6, hsp-60, the ER UPR (hsp-4, ROS response (sod-3, gst-4, and xenobiotic detoxification (gst-4. We then screened for other gene inactivations that disrupt the induction of these responses by xenobiotic or genetic triggers, identifying 29 gene inactivations required for cytoprotective gene expression. If cytoprotective responses contribute directly to lifespan extension, inactivation of these genes would be expected to compromise the extension of lifespan conferred by decreased insulin/IGF-1 signaling, caloric restriction, or the inhibition of mitochondrial function. We find that inactivation of 25 of 29 cytoprotection-regulatory genes shortens the extension of longevity normally induced by decreased insulin/IGF-1 signaling, disruption of mitochondrial function, or caloric restriction, without disrupting normal longevity nearly as dramatically. These data demonstrate that induction of cytoprotective pathways is central to longevity extension and identify a large set of new genetic components of the pathways that detect cellular damage and couple that detection to downstream cytoprotective effectors.

GABA metabolism pathway genes, UGA1 and GAD1, regulate replicative lifespan in Saccharomycescerevisiae

Energy Technology Data Exchange (ETDEWEB)

Kamei, Yuka; Tamura, Takayuki [Department of Bioscience, Faculty of Bioscience, Nagahama Institute of Bio-Science and Technology, 1266 Tamura, Nagahama, Shiga 526-0829 (Japan); Yoshida, Ryo [Department of Biotechnology, Graduate School of Engineering, Osaka University, 2-1 Yamadaoka, Suita, Osaka 565-0871 (Japan); Ohta, Shinji [Department of Bioscience, Faculty of Bioscience, Nagahama Institute of Bio-Science and Technology, 1266 Tamura, Nagahama, Shiga 526-0829 (Japan); Fukusaki, Eiichiro [Department of Biotechnology, Graduate School of Engineering, Osaka University, 2-1 Yamadaoka, Suita, Osaka 565-0871 (Japan); Mukai, Yukio, E-mail: y_mukai@nagahama-i-bio.ac.jp [Department of Bioscience, Faculty of Bioscience, Nagahama Institute of Bio-Science and Technology, 1266 Tamura, Nagahama, Shiga 526-0829 (Japan)

2011-04-01

extension. These results strongly suggest reduced activity of the GABA-metabolizing enzymes extends lifespan by shifting carbon metabolism toward respiration, as calorie restriction does.

GABA metabolism pathway genes, UGA1 and GAD1, regulate replicative lifespan in Saccharomycescerevisiae

International Nuclear Information System (INIS)

Kamei, Yuka; Tamura, Takayuki; Yoshida, Ryo; Ohta, Shinji; Fukusaki, Eiichiro; Mukai, Yukio

2011-01-01

reduced activity of the GABA-metabolizing enzymes extends lifespan by shifting carbon metabolism toward respiration, as calorie restriction does.

Differential Regulation of Hippocampal IGF-1-Associated Signaling Proteins by Dietary Restriction in Aging Mouse.

Science.gov (United States)

Hadem, Ibanylla Kynjai Hynniewta; Sharma, Ramesh

2017-08-01

Time-dependent alterations in several biological processes of an organism may be characterized as aging. One of the effects of aging is the decline in cognitive functions. Dietary restriction (DR), an intervention where the consumption of food is lessened but without malnutrition, is a well-established mechanism that has a wide range of important outcomes including improved health span, delayed aging, and extension of lifespan of various species. It also plays a beneficial role in protecting against age-dependent deterioration of cognitive functions, and has neuroprotective properties against neurodegenerative diseases. Insulin-like growth factor (IGF)-1 plays an important role in the regulation of cellular and tissue functions, and relating to the aging process the most important pathway of IGF-1 is the phosphatidylinositol 3-kinase (PI3K) and protein kinase B (Akt/PKB) signaling cascade. Although many have studied the changes in the level of IGF-1 and its effect on neural proliferation, the downstream signaling proteins have not been fully elucidated. Hence in the present investigation, the IGF-1 gene expression and the normal endogenous levels of IGF1R (IGF-1 receptor), PI3K, Akt, pAkt, and pFoxO in the hippocampus of young, adult, and old mice were determined using real-time PCR and Western blot analyses. The effects of DR on these protein levels were also studied. Results showed a decrease in the levels of IGF-1, IGF1R, PI3K, and pAkt, while pFoxO level increased with respect to age. Under DR, these protein levels are maintained in adult mice, but old mice displayed diminished expression levels of these proteins as compared to ad libitum-fed mice. Maintenance of PI3K/Akt pathway results in the phosphorylation of FoxOs, necessary for the enhancement of neural proliferation and survival in adult mice. The down-regulation of IGF-I signaling, as observed in old mice, leads to increasing the activity of FoxO factors that may be important for the neuroprotective

The role of the TOR pathway in mediating the link between nutrition and longevity.

Science.gov (United States)

Lushchak, Oleh; Strilbytska, Olha; Piskovatska, Veronika; Storey, Kenneth B; Koliada, Alexander; Vaiserman, Alexander

2017-06-01

The target of rapamycin (TOR) pathway integrates signals from extracellular and intracellular agents, such as growth factors, nutrients, mediators of energy balance, oxygen availability and other environmental cues. It allows the regulation of multiple cellular processes including protein and lipid synthesis, ribosome biogenesis, autophagy and metabolic processes. Being conserved across different phyla, TOR regulates longevity of various organisms in response to dietary conditions. In this review we described the main components of the TOR pathway and its upstream effectors and downstream processes in relation to aging. The potential contribution of the TOR pathway in lifespan-extending effects of varied dietary interventions, and the anti-aging drugs rapamycin and metformin direct or indirect regulation of TOR activity in yeasts, worms, flies and mammals are also discussed. Copyright © 2017 Elsevier B.V. All rights reserved.

Animal lifespan and human influence

Science.gov (United States)

Guo, Q.; Yang, S.

2002-01-01

Lifespan differs radically among organisms ever lived on earth, even among those roughly similar in size, shape, form, and physiology; Yet, in general, there exists a strong positive relationship between lifespan and body size. Although lifespans of humans and human-related (domestic) animals are becoming increasingly longer than that of other animals of similar sizes, the slope of the regression (lifespan-body size) line and the intercepts have been surprisingly stable over the course of the dramatic human population growth, indicating substantial depression in lifespans of many other animals probably due to shrunk and fragmented natural habitats. This article addresses two questions related to the lifespan-size relationship: (1) what caused the exceptions (e.g., a few remote human-related animals are also located above the regression line with great residuals) and why (e.g., could brain size or intelligence be a covariate in addition to body size in predicting lifespan?), and (2) whether continued human activities can eventually alter the ' natural' regression line in the future, and if so, how much. We also suggest similar research efforts to be extended to the plant world as well.

Components of an Anticancer Diet: Dietary Recommendations, Restrictions and Supplements of the Bill Henderson Protocol

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Laurie Heilman Bell

2010-12-01

Full Text Available The use of complementary and alternative medicines including dietary supplements, herbals and special diets to prevent or treat disease continues to be popular. The following paper provides a description of an alternative dietary approach to the self-management and treatment of cancer, the Bill Henderson Protocol (BHP. This diet encourages daily intake of raw foods, a combination of cottage cheese and flaxseed oil and a number of supplements. Some foods and food groups are restricted (e.g., gluten, meat, dairy. Early background theory that contributed to the protocol’s development is presented as is a summary of relevant evidence concerning the anti-cancer fighting properties of the individual components. Supplement intake is considered in relation to daily recommended intakes. Challenges and risks to protocol adherence are discussed. As with many complementary and alternative interventions, clear evidence of this dietary protocol’s safety and efficacy is lacking. Consumers of this protocol may require guidance on the ability of this protocol to meet their individual nutritional needs.

Differences between health and ethical vegetarians. Strength of conviction, nutrition knowledge, dietary restriction, and duration of adherence.

Science.gov (United States)

Hoffman, Sarah R; Stallings, Sarah F; Bessinger, Raymond C; Brooks, Gary T

2013-06-01

Little research has been published concerning the differences between health oriented and ethically oriented vegetarians. The present study compared differences in conviction, nutrition knowledge, dietary restriction, and duration of adherence to vegetarianism between the two groups. Subjects completed an online survey and were grouped by original reason for becoming vegetarian (n=292, 58 health, 234 ethical), and current reason for remaining vegetarian (n=281, 49 health, 232 ethical). Whether grouped by current or original motivation, ethical vegetarians scored higher on the conviction instrument than health vegetarians and exhibited somewhat greater dietary restriction (significant when grouped by current motivation) and had been vegetarian for longer (significant when grouped by original motivation). Nutrition knowledge did not differ between the two groups. The results suggest that ethical vegetarians could experience stronger feelings of conviction and consume fewer animal products than health vegetarians, and may remain vegetarian longer. More research is necessary to understand how vegetarians' eating behaviors are influenced by their motivational profiles. Copyright © 2013 Elsevier Ltd. All rights reserved.

Lifespan extension by dietary intervention in a mouse model of Cockayne syndrome uncouples early postnatal development from segmental progeria.

Science.gov (United States)

Brace, Lear E; Vose, Sarah C; Vargas, Dorathy F; Zhao, Shuangyun; Wang, Xiu-Ping; Mitchell, James R

2013-12-01

Cockayne syndrome (CS) is a rare autosomal recessive segmental progeria characterized by growth failure, lipodystrophy, neurological abnormalities, and photosensitivity, but without skin cancer predisposition. Cockayne syndrome life expectancy ranges from 5 to 16 years for the two most severe forms (types II and I, respectively). Mouse models of CS have thus far been of limited value due to either very mild phenotypes, or premature death during postnatal development prior to weaning. The cause of death in severe CS models is unknown, but has been attributed to extremely rapid aging. Here, we found that providing mutant pups with soft food from as late as postnatal day 14 allowed survival past weaning with high penetrance independent of dietary macronutrient balance in a novel CS model (Csa(-/-) | Xpa(-/-)). Survival past weaning revealed a number of CS-like symptoms including small size, progressive loss of adiposity, and neurological symptoms, with a maximum lifespan of 19 weeks. Our results caution against interpretation of death before weaning as premature aging, and at the same time provide a valuable new tool for understanding mechanisms of progressive CS-related progeroid symptoms including lipodystrophy and neurodysfunction. © 2013 the Anatomical Society and John Wiley & Sons Ltd.

Dietary Advanced Glycation End Products and Aging

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Karen Chapman-Novakofski

2010-12-01

Full Text Available Advanced glycation end products (AGEs are a heterogeneous, complex group of compounds that are formed when reducing sugar reacts in a non-enzymatic way with amino acids in proteins and other macromolecules. This occurs both exogenously (in food and endogenously (in humans with greater concentrations found in older adults. While higher AGEs occur in both healthy older adults and those with chronic diseases, research is progressing to both quantify AGEs in food and in people, and to identify mechanisms that would explain why some human tissues are damaged, and others are not. In the last twenty years, there has been increased evidence that AGEs could be implicated in the development of chronic degenerative diseases of aging, such as cardiovascular disease, Alzheimer’s disease and with complications of diabetes mellitus. Results of several studies in animal models and humans show that the restriction of dietary AGEs has positive effects on wound healing, insulin resistance and cardiovascular diseases. Recently, the effect of restriction in AGEs intake has been reported to increase the lifespan in animal models. This paper will summarize the work that has been published for both food AGEs and in vivo AGEs and their relation with aging, as well as provide suggestions for future research.

Emodin extends lifespan of Caenorhabditis elegans through insulin/IGF-1 signaling pathway depending on DAF-16 and SIR-2.1.

Science.gov (United States)

Zhao, Xuan; Lu, Lulu; Qi, Yonghao; Li, Miao; Zhou, Lijun

2017-10-01

The naturally occurring anthraquinone emodin has been serving primarily as an anti-bacterial and anti-inflammatory agent. However, little is known about its potential on anti-aging. This investigation examined the effect of emodin on lifespan and focused on its physiological molecular mechanisms in vivo. Using Caenorhabditis elegans (C. elegans) as an animal model, we found emodin could extend lifespan of worms and improve their antioxidant capacity. Our mechanistic studies revealed that emodin might function via insulin/IGF-1 signaling (IIS) pathway involving, specifically the core transcription factor DAF-16. Quantitative RT-PCR results illustrated that emodin up-regulated transcription of DAF-16 target genes which express antioxidants to promote antioxidant capacity and lifespan of worms. In addition, attenuated effect in sir-2.1 mutants suggests that emodin likely functioned in a SIR-2.1-dependent manner. Our study uncovers a novel role of emodin in prolonging lifespan and supports the understanding of emodin being a beneficial dietary supplement.

Requirements for capsid-binding and an effector function in TRIMCyp-mediated restriction of HIV-1

International Nuclear Information System (INIS)

Diaz-Griffero, Felipe; Vandegraaff, Nick; Li Yuan; McGee-Estrada, Kathleen; Stremlau, Matthew; Welikala, Sohanya; Si Zhihai; Engelman, Alan; Sodroski, Joseph

2006-01-01

In owl monkeys, a retrotransposition event replaced the gene encoding the retroviral restriction factor TRIM5α with one encoding TRIMCyp, a fusion between the RING, B-box 2 and coiled-coil domains of TRIM5 and cyclophilin A. TRIMCyp restricts human immunodeficiency virus (HIV-1) infection by a mechanism dependent on the interaction of the cyclophilin A moiety and the HIV-1 capsid protein. Here, we show that infection by retroviruses other than HIV-1 can be restricted by TRIMCyp, providing an explanation for the evolutionary retention of the TRIMCyp gene in owl monkey lineages. The TRIMCyp-mediated block to HIV-1 infection occurs before the earliest step of reverse transcription. TRIMCyp-mediated restriction involves at least two functions: (1) capsid binding, which occurs most efficiently for trimeric TRIMCyp proteins that retain the coiled-coil and cyclophilin A domains, and (2) an effector function that depends upon the B-box 2 domain

Fasting, circadian rhythms, and time restricted feeding in healthy lifespan

OpenAIRE

Longo, Valter D.; Panda, Satchidananda

2016-01-01

Feeding in most animals is confined to a defined period, leaving short periods of fasting that coincide with sleep. Fasting enables organisms to enter alternative metabolic phases, which rely less on glucose and more on ketone body-like carbon sources. Both intermittent and periodic fasting result in benefits ranging from prevention to the enhanced treatment of diseases. Similarly, time-restricted feeding (TRF), in which feeding time is restricted to certain hours of the day, allows the daily...

Caloric restriction shortens lifespan through an increase in lipid peroxidation, inflammation and apoptosis in the G93A mouse, an animal model of ALS.

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Barkha P Patel

2010-02-01

Full Text Available Caloric restriction (CR extends lifespan through a reduction in oxidative stress, delays the onset of morbidity and prolongs lifespan. We previously reported that long-term CR hastened clinical onset, disease progression and shortened lifespan, while transiently improving motor performance in G93A mice, a model of amyotrophic lateral sclerosis (ALS that shows increased free radical production. To investigate the long-term CR-induced pathology in G93A mice, we assessed the mitochondrial bioenergetic efficiency and oxidative capacity (CS--citrate synthase content and activity, cytochrome c oxidase--COX activity and protein content of COX subunit-I and IV and UCP3-uncoupling protein 3, oxidative damage (MDA--malondialdehyde and PC--protein carbonyls, antioxidant enzyme capacity (Mn-SOD, Cu/Zn-SOD and catalase, inflammation (TNF-alpha, stress response (Hsp70 and markers of apoptosis (Bax, Bcl-2, caspase 9, cleaved caspase 9 in their skeletal muscle. At age 40 days, G93A mice were divided into two groups: Ad libitum (AL; n = 14; 7 females or CR (n = 13; 6 females, with a diet equal to 60% of AL. COX/CS enzyme activity was lower in CR vs. AL male quadriceps (35%, despite a 2.3-fold higher COX-IV/CS protein content. UCP3 was higher in CR vs. AL females only. MnSOD and Cu/Zn-SOD were higher in CR vs. AL mice and CR vs. AL females. MDA was higher (83% in CR vs. AL red gastrocnemius. Conversely, PC was lower in CR vs. AL red (62% and white (30% gastrocnemius. TNF-alpha was higher (52% in CR vs. AL mice and Hsp70 was lower (62% in CR vs. AL quadriceps. Bax was higher in CR vs. AL mice (41% and CR vs. AL females (52%. Catalase, Bcl-2 and caspases did not differ. We conclude that CR increases lipid peroxidation, inflammation and apoptosis, while decreasing mitochondrial bioenergetic efficiency, protein oxidation and stress response in G93A mice.

Long-term dietary restriction up-regulates activity and expression of ...

Indian Academy of Sciences (India)

T Majaw

2017-04-18

Apr 18, 2017 ... ing (24 h fasting and re-feeding) reduces 30-40% of food intake (Qiu et al ... tween low calorie intake and increased lifespan (Anderson and Weindruch ..... may enter the TCA cycle and increase the intermediate flux for greater ...

Effects of Dietary Sodium Restriction in Kidney Transplant Recipients Treated With Renin-Angiotensin-Aldosterone System Blockade: A Randomized Clinical Trial

NARCIS (Netherlands)

de Vries, Laura V.; Dobrowolski, Linn C.; van den Bosch, Jacqueline J. O. N.; Riphagen, Ineke J.; Krediet, C. T. Paul; Bemelman, Frederike J.; Bakker, Stephan J. L.; Navis, Gerjan

2016-01-01

In patients with chronic kidney disease receiving renin-angiotensin-aldosterone system (RAAS) blockade, dietary sodium restriction is an often-used treatment strategy to reduce blood pressure (BP) and albuminuria. Whether these effects extend to kidney transplant recipients is unknown. We therefore

Effects of Dietary Sodium Restriction in Kidney Transplant Recipients Treated With Renin-Angiotensin-Aldosterone System Blockade : A Randomized Clinical Trial

NARCIS (Netherlands)

de Vries, Laura V; Dobrowolski, Linn C; van den Bosch, Jacqueline J O N; Riphagen, Ineke J; Krediet, C T Paul; Bemelman, Frederike J; Bakker, Stephan J L; Navis, Gerjan

BACKGROUND: In patients with chronic kidney disease receiving renin-angiotensin-aldosterone system (RAAS) blockade, dietary sodium restriction is an often-used treatment strategy to reduce blood pressure (BP) and albuminuria. Whether these effects extend to kidney transplant recipients is unknown.

Boosting ATM activity alleviates aging and extends lifespan in a mouse model of progeria.

Science.gov (United States)

Qian, Minxian; Liu, Zuojun; Peng, Linyuan; Tang, Xiaolong; Meng, Fanbiao; Ao, Ying; Zhou, Mingyan; Wang, Ming; Cao, Xinyue; Qin, Baoming; Wang, Zimei; Zhou, Zhongjun; Wang, Guangming; Gao, Zhengliang; Xu, Jun; Liu, Baohua

2018-05-02

DNA damage accumulates with age (Lombard et al., 2005). However, whether and how robust DNA repair machinery promotes longevity is elusive. Here, we demonstrate that ATM-centered DNA damage response (DDR) progressively declines with senescence and age, while low dose of chloroquine (CQ) activates ATM, promotes DNA damage clearance, rescues age-related metabolic shift, and prolongs replicative lifespan. Molecularly, ATM phosphorylates SIRT6 deacetylase and thus prevents MDM2-mediated ubiquitination and proteasomal degradation. Extra copies of Sirt6 extend lifespan in Atm-/- mice, with restored metabolic homeostasis. Moreover, the treatment with CQ remarkably extends lifespan of Caenorhabditis elegans , but not the ATM-1 mutants. In a progeria mouse model with low DNA repair capacity, long-term administration of CQ ameliorates premature aging features and extends lifespan. Thus, our data highlights a pro-longevity role of ATM, for the first time establishing direct causal links between robust DNA repair machinery and longevity, and providing therapeutic strategy for progeria and age-related metabolic diseases. © 2018, Qian et al.

NAD+ metabolite levels as a function of vitamins and calorie restriction: evidence for different mechanisms of longevity

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Song Peng

2010-02-01

Full Text Available Abstract Background NAD+ is a coenzyme for hydride transfer enzymes and a substrate for sirtuins and other NAD+-dependent ADPribose transfer enzymes. In wild-type Saccharomyces cerevisiae, calorie restriction accomplished by glucose limitation extends replicative lifespan in a manner that depends on Sir2 and the NAD+ salvage enzymes, nicotinic acid phosphoribosyl transferase and nicotinamidase. Though alterations in the NAD+ to nicotinamide ratio and the NAD+ to NADH ratio are anticipated by models to account for the effects of calorie restriction, the nature of a putative change in NAD+ metabolism requires analytical definition and quantification of the key metabolites. Results Hydrophilic interaction chromatography followed by tandem electrospray mass spectrometry were used to identify the 12 compounds that constitute the core NAD+ metabolome and 6 related nucleosides and nucleotides. Whereas yeast extract and nicotinic acid increase net NAD+ synthesis in a manner that can account for extended lifespan, glucose restriction does not alter NAD+ or nicotinamide levels in ways that would increase Sir2 activity. Conclusions The results constrain the possible mechanisms by which calorie restriction may regulate Sir2 and suggest that provision of vitamins and calorie restriction extend lifespan by different mechanisms.

Prolonged REM sleep restriction induces metabolic syndrome-related changes: Mediation by pro-inflammatory cytokines.

Science.gov (United States)

Venancio, Daniel Paulino; Suchecki, Deborah

2015-07-01

Chronic sleep restriction in human beings results in metabolic abnormalities, including changes in the control of glucose homeostasis, increased body mass and risk of cardiovascular disease. In rats, 96h of REM sleep deprivation increases caloric intake, but retards body weight gain. Moreover, this procedure increases the expression of pro-inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6), which may be involved with the molecular mechanism proposed to mediate insulin resistance. The goal of the present study was to assess the effects of a chronic protocol of sleep restriction on parameters of energy balance (food intake and body weight), leptin plasma levels and its hypothalamic receptors and mediators of the immune system in the retroperitoneal adipose tissue (RPAT). Thirty-four Wistar rats were distributed in control (CTL) and sleep restriction groups; the latter was kept onto individual narrow platforms immersed in water for 18h/day (from 16:00h to 10:00h), for 21days (SR21). Food intake was assessed daily, after each sleep restriction period and body weight was measured daily, after the animals were taken from the sleep deprivation chambers. At the end of the 21day of sleep restriction, rats were decapitated and RPAT was obtained for morphological and immune functional assays and expression of insulin receptor substrate 1 (IRS-1) was assessed in skeletal muscle. Another subset of animals was used to evaluate blood glucose clearance. The results replicated previous findings on energy balance, e.g., increased food intake and reduced body weight gain. There was a significant reduction of RPAT mass (pmetabolic syndrome-related alterations that may be mediated by inflammation of the RPAT. Copyright © 2014 Elsevier Inc. All rights reserved.

Suppression of APOBEC3-mediated restriction of HIV-1 by Vif

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Yuqing eFeng

2014-08-01

Full Text Available The APOBEC3 restriction factors are a family of deoxycytidine deaminases that are able to suppress replication of viruses with a single-stranded DNA intermediate by inducing mutagenesis and functional inactivation of the virus. Of the seven human APOBEC3 enzymes, only APOBEC3-D, -F, -G, and -H appear relevant to restriction of HIV-1 in CD4+ T cells and will be the focus of this review. The restriction of HIV-1 occurs most potently in the absence of HIV-1 Vif that induces polyubiquitination and degradation of APOBEC3 enzymes through the proteasome pathway. To restrict HIV-1, APOBEC3 enzymes must be encapsidated into budding virions. Upon infection of the target cell during reverse transcription of the HIV-1 RNA into (-DNA APOBEC3 enzymes deaminate cytosines to forms uracils in single-stranded (- DNA regions. Upon replication of the (-DNA to (+DNA, the HIV-1 reverse transcriptase incorporates adenines opposite the uracils thereby inducing C/G to T/A mutations that can functionally inactivate HIV-1. APOBEC3G is the most studied APOBEC3 enzyme and it is known that Vif attempts to thwart APOBEC3 function not only by inducing its proteasomal degradation but by several degradation-independent mechanisms such as inhibiting APOBEC3G virion encapsidation, mRNA translation, and for those APOBEC3G molecules that still become virion encapsidated, Vif can inhibit APOBEC3G mutagenic activity. Although most Vif variants can induce efficient degradation of APOBEC3-D, -F, and -G, there appears to be differential sensitivity to Vif-mediated degradation for APOBEC3H. This review examines APOBEC3-mediated HIV restriction mechanisms, how Vif acts as a substrate receptor for a Cullin5 ubiquitin ligase complex to induce degradation of APOBEC3s, and the determinants and functional consequences of the APOBEC3 and Vif interaction from a biological and biochemical perspective.

Dietary fat and not calcium supplementation or dairy product consumption is associated with changes in anthropometrics during a randomized, placebo-controlled energy-restriction trial

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Zemel Michael B

2011-10-01

Full Text Available Abstract Insufficient calcium intake has been proposed to cause unbalanced energy partitioning leading to obesity. However, weight loss interventions including dietary calcium or dairy product consumption have not reported changes in lipid metabolism measured by the plasma lipidome. Methods The objective of this study was to determine the relationships between dairy product or supplemental calcium intake with changes in the plasma lipidome and body composition during energy restriction. A secondary objective of this study was to explore the relationships among calculated macronutrient composition of the energy restricted diet to changes in the plasma lipidome, and body composition during energy restriction. Overweight adults (n = 61 were randomized into one of three intervention groups including a deficit of 500kcal/d: 1 placebo; 2 900 mg/d calcium supplement; and 3 3-4 servings of dairy products/d plus a placebo supplement. Plasma fatty acid methyl esters of cholesterol ester, diacylglycerol, free fatty acids, lysophosphatidylcholine, phosphatidylcholine, phosphatidylethanolamine and triacylglycerol were quantified by capillary gas chromatography. Results After adjustments for energy and protein (g/d intake, there was no significant effect of treatment on changes in weight, waist circumference or body composition. Plasma lipidome did not differ among dietary treatment groups. Stepwise regression identified correlations between reported intake of monounsaturated fat (% of energy and changes in % lean mass (r = -0.44, P P Conclusions Dairy product consumption or calcium supplementation during energy restriction over the course of 12 weeks did not affect plasma lipids. Independent of calcium and dairy product consumption, short-term energy restriction altered body composition. Reported dietary fat composition of energy restricted diets was associated with the degree of change in body composition in these overweight and obese individuals.

RELATION BETWEEN GLUCOLIPID PROFILE AND SMALL INTESTINE HISTOLOGICAL PATTERNS IN DIABETIC RATS EXPOSED TO AN INTERMITTENT DIETARY RESTRICTION

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Noriyuki Hisano

2009-01-01

Full Text Available The effects of an intermittent and prolonged dietary restriction on biochemical variables and histological small intestinal patterns in 12-month-old male eSMT rats are examined. These spontaneously diabetic animals were separated in two groups after weaning: 10 rats fed ad libitum with standard rat chow and 10 rats fed a restricted diet by deprivation of the same food for 24 hours every 72. At 12 months of age, animals were weighed and euthanized after tail vein bleeding for plasma analysis (glycemia- both fasting and 120 minutes after an oral glucose challenge-, triglyceridemia and total cholesterolemia. Small intestines were removed, weighed and measured in length.Intestinal specimens were fixed, embedded in paraffin, semi serially cut at 6 µm and stained with PAS-Hematoxilyn and Hematoxilyn-Eosin. Histometry was performed through a linear devise attached to ocular lens and lectin histochemistry was accomplished employing Canavalis ensiformis, Dolichos biflorus, Arachis hypogea, Ulex europaeus-I, Triticum vulgaris, Ricinus communis and Soy Bean (Glicine Max Agglutinin. Essentially, eSMT rats, a suitable animal model for studying diabetes and/or its complications, revealed at 12 months of age after undergoing the dietary restriction: 1.- An expected improvement in body weight and determined biochemical variables (fasting and after glucose overload glycemias, triglyceridemia and total cholesterolemia without reaching euglycemic values. 2.- Changes in most of the analyzed histometric patterns with no relevant reflection on morphometric ones, and 3.- No modifications in lectinhistochemical patterns.

Can we use the epigenetic bioactivity of caloric restriction and phytochemicals to promote healthy ageing?

Czech Academy of Sciences Publication Activity Database

Christodoulou, M.S.; Thomas, A.; Poulain, S.; Vidakovic, M.; Lahtela-Kakkonen, M.; Matulis, D.; Bertrand, P.; Bártová, Eva

2014-01-01

Roč. 5, č. 12 (2014), s. 1804-1820 ISSN 2040-2503 Institutional support: RVO:68081707 Keywords : CORONARY- HEART - DISEASE * LIFE-SPAN * DIETARY POLYPHENOLS Subject RIV: BO - Biophysics Impact factor: 2.495, year: 2014

Global mapping of protein phosphorylation events identifies novel signalling hubs mediating fatty acid starvation responses in Saccharomyces cerevisiae

DEFF Research Database (Denmark)

Pultz, Dennis; Bennetzen, Martin; Rødkær, Steven Vestergaard

2011-01-01

Dietary restriction (DR) extends the life span of multiple species, ranging from single-celled organisms like yeast to mammals. This increase in longevity by dietary restriction is coupled to profound beneficial effects on age-related pathology. Despite the number of studies on DR...... and the physiological changes DR induces, only little is known about the genetics and signalling networks, which regulate the DR response. We have recently shown that inhibition of fatty acid synthesis in Saccharomyces cerevisiae induces autophagy mediated by TORC1 signalling and affects life span. In the present study...... in a temporal manner in response to inhibition of fatty acid synthesis by cerulenin. By in silico analysis of these phosphorylation events, we have identified the major downstream regulated processes and signalling networks mediating the cellular response to fatty acid starvation. The analysis further...

Macronutrients and caloric intake in health and longevity.

Science.gov (United States)

Solon-Biet, Samantha M; Mitchell, Sarah J; de Cabo, Rafael; Raubenheimer, David; Le Couteur, David G; Simpson, Stephen J

2015-07-01

Both lifespan and healthspan are influenced by nutrition, with nutritional interventions proving to be robust across a wide range of species. However, the relationship between nutrition, health and aging is still not fully understood. Caloric restriction is the most studied dietary intervention known to extend life in many organisms, but recently the balance of macronutrients has been shown to play a critical role. In this review, we discuss the current understanding regarding the impact of calories and macronutrient balance in mammalian health and longevity, and highlight the key nutrient-sensing pathways that mediate the effects of nutrition on health and ageing. © 2015 Society for Endocrinology.

Dietary cholesterol, heart disease risk and cognitive dissonance.

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McNamara, Donald J

2014-05-01

In the 1960s, the thesis that dietary cholesterol contributes to blood cholesterol and heart disease risk was a rational conclusion based on the available science at that time. Fifty years later the research evidence no longer supports this hypothesis yet changing the dietary recommendation to limit dietary cholesterol has been a slow and at times contentious process. The preponderance of the clinical and epidemiological data accumulated since the original dietary cholesterol restrictions were formulated indicate that: (1) dietary cholesterol has a small effect on the plasma cholesterol levels with an increase in the cholesterol content of the LDL particle and an increase in HDL cholesterol, with little effect on the LDL:HDL ratio, a significant indicator of heart disease risk, and (2) the lack of a significant relationship between cholesterol intake and heart disease incidence reported from numerous epidemiological surveys. Over the last decade, many countries and health promotion groups have modified their dietary recommendations to reflect the current evidence and to address a now recognised negative consequence of ineffective dietary cholesterol restrictions (such as inadequate choline intake). In contrast, health promotion groups in some countries appear to suffer from cognitive dissonance and continue to promote an outdated and potentially hazardous dietary recommendation based on an invalidated hypothesis. This review evaluates the evidence for and against dietary cholesterol restrictions and the potential consequences of such restrictions.

The Influence of Dietary Fat Source on Life Span in Calorie Restricted Mice.

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López-Domínguez, José A; Ramsey, Jon J; Tran, Dianna; Imai, Denise M; Koehne, Amanda; Laing, Steven T; Griffey, Stephen M; Kim, Kyoungmi; Taylor, Sandra L; Hagopian, Kevork; Villalba, José M; López-Lluch, Guillermo; Navas, Plácido; McDonald, Roger B

2015-10-01

Calorie restriction (CR) without malnutrition extends life span in several animal models. It has been proposed that a decrease in the amount of polyunsaturated fatty acids (PUFAs), and especially n-3 fatty acids, in membrane phospholipids may contribute to life span extension with CR. Phospholipid PUFAs are sensitive to dietary fatty acid composition, and thus, the purpose of this study was to determine the influence of dietary lipids on life span in CR mice. C57BL/6J mice were assigned to four groups (a 5% CR control group and three 40% CR groups) and fed diets with soybean oil (high in n-6 PUFAs), fish oil (high in n-3 PUFAs), or lard (high in saturated and monounsaturated fatty acids) as the primary lipid source. Life span was increased (p Life span was also increased (p life span in mice on CR, and suggest that a diet containing a low proportion of PUFAs and high proportion of monounsaturated and saturated fats may maximize life span in animals maintained on CR. © The Author 2014. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Influences of different dietary energy level on sheep testicular development associated with AMPK/ULK1/autophagy pathway.

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Pang, Jing; Li, Fengzhe; Feng, Xu; Yang, Hua; Han, Le; Fan, Yixuan; Nie, Haitao; Wang, Zhen; Wang, Feng; Zhang, Yanli

2018-03-01

Energy balance is an important feature for spermatozoa production in the testis. The 5'-AMP-activated protein kinase (AMPK) is a sensor of cell energy, has been implicated as a mediator between gonadal function and energy balance. Herein, we intended to determine the physiological effects of AMPK on testicular development in feed energy restricted and compensated pre-pubertal rams. Lambs had restricted feeding for 2 months and then provided compensatory feeding for another 3 months. Feed levels were 100%(control), 15% and 30% of energy restriction (ER) diets, respectively. The results showed that lambs fed the 30% ER diet had significantly lower testicular weight (P energy requirement after restriction. Taken together, dietary energy levels influence testicular development through autophagy and apoptosis interplay mediated by AMPK-ULK1 signal pathway, which also indicates the important role of the actions of AMPK in the testis homeostasis. Copyright © 2017 Elsevier Inc. All rights reserved.

Dietary restriction but not angiotensin II type 1 receptor blockade improves DNA damage-related vasodilator dysfunction in rapidly aging Ercc1Δ/- mice.

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Wu, Haiyan; van Thiel, Bibi S; Bautista-Niño, Paula K; Reiling, Erwin; Durik, Matej; Leijten, Frank P J; Ridwan, Yanto; Brandt, Renata M C; van Steeg, Harry; Dollé, Martijn E T; Vermeij, Wilbert P; Hoeijmakers, Jan H J; Essers, Jeroen; van der Pluijm, Ingrid; Danser, A H Jan; Roks, Anton J M

2017-08-01

DNA damage is an important contributor to endothelial dysfunction and age-related vascular disease. Recently, we demonstrated in a DNA repair-deficient, prematurely aging mouse model ( Ercc1 Δ/- mice) that dietary restriction (DR) strongly increases life- and health span, including ameliorating endothelial dysfunction, by preserving genomic integrity. In this mouse mutant displaying prominent accelerated, age-dependent endothelial dysfunction we investigated the signaling pathways involved in improved endothelium-mediated vasodilation by DR, and explore the potential role of the renin-angiotensin system (RAS). Ercc1 Δ/- mice showed increased blood pressure and decreased aortic relaxations to acetylcholine (ACh) in organ bath experiments. Nitric oxide (NO) signaling and phospho-Ser 1177 -eNOS were compromised in Ercc1 Δ / - DR improved relaxations by increasing prostaglandin-mediated responses. Increase of cyclo-oxygenase 2 and decrease of phosphodiesterase 4B were identified as potential mechanisms. DR also prevented loss of NO signaling in vascular smooth muscle cells and normalized angiotensin II (Ang II) vasoconstrictions, which were increased in Ercc1 Δ/- mice. Ercc1 Δ/ - mutants showed a loss of Ang II type 2 receptor-mediated counter-regulation of Ang II type 1 receptor-induced vasoconstrictions. Chronic losartan treatment effectively decreased blood pressure, but did not improve endothelium-dependent relaxations. This result might relate to the aging-associated loss of treatment efficacy of RAS blockade with respect to endothelial function improvement. In summary, DR effectively prevents endothelium-dependent vasodilator dysfunction by augmenting prostaglandin-mediated responses, whereas chronic Ang II type 1 receptor blockade is ineffective. © 2017 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

Cultural factors influencing dietary and fluid restriction behaviour: perceptions of older Chinese patients with heart failure.

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Rong, Xiaoshan; Peng, Youqing; Yu, Hai-Ping; Li, Dan

2017-03-01

To explore the cultural factors related to dietary and fluid restriction behaviours among older Chinese patients. Excess dietary sodium and fluid intake are risk factors contributing to the worsening and rehospitalisation for heart failure in older patients. Managing the complex fluid and diet requirements of heart failure patients is challenging and is made more complicated by cultural variations in self-management behaviours in response to a health threat. Qualitative study using semi-structured in interviews and framework analysis. The design of this study is qualitative descriptive. Semi-structured in-depth interviews were conducted with 15 heart failure patients. Data were analysed through content analysis. Seven cultural themes emerged from the qualitative data: the values placed on health and illness, customary way of life, preference for folk care and the Chinese healthcare system, and factors related to kinship and social ties, religion, economics and education. Dietary change and management in response to illness, including heart failure, is closely related to individuals' cultural background. Healthcare providers should have a good understanding of cultural aspects that can influence patients' conformity to medical recommendations. Heart failure patients need support that considers their cultural needs. Healthcare providers must have a good understanding of the experiences of people from diverse cultural backgrounds. © 2016 John Wiley & Sons Ltd.

Calorie restriction and dwarf mice in gerontological research.

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McKee Alderman, J; DePetrillo, Michael A; Gluesenkamp, Angela M; Hartley, Antonia C; Verhoff, S Veronica; Zavodni, Katherine L; Combs, Terry P

2010-01-01

What aging process is delayed by calorie restriction (CR) and mutations that produce long-lived dwarf mice? From 1935 until 1996, CR was the only option for increasing the maximum lifespan of laboratory rodents. In 1996, the mutation producing the Ames dwarf mouse (Prop-1(-/-)) was reported to increase lifespan. Since 1996, other gene mutations that cause dwarfism or lower body weight have been reported to increase the lifespan of mice. The recent discovery of long-lived mutant dwarf mice provides an opportunity to investigate common features between CR and dwarf models. Both CR and dwarf mutations increase insulin sensitivity. Elevated insulin sensitivity reduces oxidative stress, a potential cause of aging. The elevation of liver insulin sensitivity by the hormone adiponectin in CR and long-lived dwarf mice can lower endogenous glucose production and raise fatty acid oxidation. Adiponectin reduction of plasma glucose in CR and long-lived dwarf mice can thereby lower age-related increases in oxidative damage and cancer. Copyright 2009 S. Karger AG, Basel.

A TRPV channel modulates C. elegans neurosecretion, larval starvation survival, and adult lifespan.

Directory of Open Access Journals (Sweden)

Brian H Lee

2008-10-01

Full Text Available For most organisms, food is only intermittently available; therefore, molecular mechanisms that couple sensation of nutrient availability to growth and development are critical for survival. These mechanisms, however, remain poorly defined. In the absence of nutrients, newly hatched first larval (L1 stage Caenorhabditis elegans halt development and survive in this state for several weeks. We isolated mutations in unc-31, encoding a calcium-activated regulator of neural dense-core vesicle release, which conferred enhanced starvation survival. This extended survival was reminiscent of that seen in daf-2 insulin-signaling deficient mutants and was ultimately dependent on daf-16, which encodes a FOXO transcription factor whose activity is inhibited by insulin signaling. While insulin signaling modulates metabolism, adult lifespan, and dauer formation, insulin-independent mechanisms that also regulate these processes did not promote starvation survival, indicating that regulation of starvation survival is a distinct program. Cell-specific rescue experiments identified a small subset of primary sensory neurons where unc-31 reconstitution modulated starvation survival, suggesting that these neurons mediate perception of food availability. We found that OCR-2, a transient receptor potential vanilloid (TRPV channel that localizes to the cilia of this subset of neurons, regulates peptide-hormone secretion and L1 starvation survival. Moreover, inactivation of ocr-2 caused a significant extension in adult lifespan. These findings indicate that TRPV channels, which mediate sensation of diverse noxious, thermal, osmotic, and mechanical stimuli, couple nutrient availability to larval starvation survival and adult lifespan through modulation of neural dense-core vesicle secretion.

Validation of the effects of small differences in dietary metabolizable energy and feed restriction in first-cycle laying hens.

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Murugesan, G R; Persia, M E

2013-05-01

An experiment was conducted to evaluate energy utilization of laying hens fed diets containing 2 ME concentrations, using response criteria including performance, BW, abdominal fat pad, and energy digestibility. The experiment was a 2 × 2 factorial with 2 feeding regimens (ad libitum and restriction fed), and 2 dietary ME levels [2,880 kcal/kg of ME (CON); and 2,790 kcal/kg of ME (LME)]. A total of 60 Hy-Line W36 first-cycle laying hens were fed experimental diets, resulting in 15 individually caged hens for each of the 4 treatments. Hens in the restriction-fed group were fed 90 g of feed per day. The CON diet was formulated to meet or exceed the NRC (1994) recommendations with 2,880 kcal/kg, whereas the LME diet was similar with the exception of a 90 kcal/kg reduction in ME. Hens were fed experimental diets for 12 wk from hen 28 to 39 wk of age. Hen day egg production, weekly feed intake, and every 2 wk, egg weights and egg mass were recorded, whereas hen BW was measured every 4 wk. Excreta samples were collected over the last 5 d of experiment to determine AMEn. Abdominal fat pads were measured individually for all hens at the end of experiment. There were no interactions between feeding regimens and dietary ME levels throughout the experiment. Feed restriction resulted in reductions (P ≤ 0.01) in hen day egg production, BW, and abdominal fat pad, indicating reduced nutrient availability to partition toward production, maintenance, and storage functions. The reduction in energy intake between CON and LME fed birds (90 kcal/kg) did not change the energy partitioned toward production or maintenance, but reduced (P = 0.03) the energy stored (reduced fat pad) of LME-fed hens. These results suggest that energy is used following the pattern of production and maintenance before storage requirements and that fat pad (energy storage) may be the most sensitive indicator of dietary energy status over short-term in Hy-Line W36 laying hens.

Fasting, circadian rhythms, and time restricted feeding in healthy lifespan

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Longo, Valter D.; Panda, Satchidananda

2016-01-01

Summary Feeding in most animals is confined to a defined period, leaving short periods of fasting that coincide with sleep. Fasting enables organisms to enter alternative metabolic phases, which rely less on glucose and more on ketone body-like carbon sources. Both intermittent and periodic fasting result in benefits ranging from prevention to the enhanced treatment of diseases. Similarly, time-restricted feeding (TRF), in which feeding time is restricted to certain hours of the day, allows the daily fasting period to last >12 h, thus imparting pleiotropic benefits in multiple organisms. Understanding the mechanistic link between nutrients and the fasting benefits is leading to the identification of fasting mimicking diets (FMDs) that achieve changes similar to those caused by fasting. Given the pleiotropic and sustained benefits of TRF and FMD, both basic science and translational research are warranted to develop fasting-associated interventions into effective and inexpensive treatments with the potential to improve healthspan. PMID:27304506

Connectivity trajectory across lifespan differentiates the precuneus from the default network.

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Yang, Zhi; Chang, Catie; Xu, Ting; Jiang, Lili; Handwerker, Daniel A; Castellanos, F Xavier; Milham, Michael P; Bandettini, Peter A; Zuo, Xi-Nian

2014-04-01

The default network of the human brain has drawn much attention due to its relevance to various brain disorders, cognition, and behavior. However, its functional components and boundaries have not been precisely defined. There is no consensus as to whether the precuneus, a hub in the functional connectome, acts as part of the default network. This discrepancy is more critical for brain development and aging studies: it is not clear whether age has a stronger impact on the default network or precuneus, or both. We used Generalized Ranking and Averaging Independent Component Analysis by Reproducibility (gRAICAR) to investigate the lifespan trajectories of intrinsic functional networks. By estimating individual-specific spatial components and aligning them across subjects, gRAICAR measures the spatial variation of component maps across a population without constraining the same components to appear in every subject. In a cross-lifespan fMRI dataset (N=126, 7-85years old), we observed stronger age dependence in the spatial pattern of a precuneus-dorsal posterior cingulate cortex network compared to the default network, despite the fact that the two networks exhibit considerable spatial overlap and temporal correlation. These results remained even when analyses were restricted to a subpopulation with very similar head motion across age. Our analyses further showed that the two networks tend to merge with increasing age. Post-hoc analyses of functional connectivity confirmed the distinguishable cross-lifespan trajectories between the two networks. Based on these observations, we proposed a dynamic model of cross-lifespan functional segregation and integration between the two networks, suggesting that the precuneus network may have a different functional role than the default network, which declines with age. These findings have implications for understanding the functional roles of the default network, gaining insight into its dynamics throughout life, and guiding

Chronological Lifespan in Yeast Is Dependent on the Accumulation of Storage Carbohydrates Mediated by Yak1, Mck1 and Rim15 Kinases

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Tang, Yingzhi; Quan, Zhenzhen; Zhang, Zhe; Oliver, Stephen G.; Zhang, Nianshu

2016-01-01

Upon starvation for glucose or any other macronutrient, yeast cells exit from the mitotic cell cycle and acquire a set of characteristics that are specific to quiescent cells to ensure longevity. Little is known about the molecular determinants that orchestrate quiescence entry and lifespan extension. Using starvation-specific gene reporters, we screened a subset of the yeast deletion library representing the genes encoding ‘signaling’ proteins. Apart from the previously characterised Rim15, Mck1 and Yak1 kinases, the SNF1/AMPK complex, the cell wall integrity pathway and a number of cell cycle regulators were shown to be necessary for proper quiescence establishment and for extension of chronological lifespan (CLS), suggesting that entry into quiescence requires the integration of starvation signals transmitted via multiple signaling pathways. The CLS of these signaling mutants, and those of the single, double and triple mutants of RIM15, YAK1 and MCK1 correlates well with the amount of storage carbohydrates but poorly with transition-phase cell cycle status. Combined removal of the glycogen and trehalose biosynthetic genes, especially GSY2 and TPS1, nearly abolishes the accumulation of storage carbohydrates and severely reduces CLS. Concurrent overexpression of GSY2 and TSL1 or supplementation of trehalose to the growth medium ameliorates the severe CLS defects displayed by the signaling mutants (rim15Δyak1Δ or rim15Δmck1Δ). Furthermore, we reveal that the levels of intracellular reactive oxygen species are cooperatively controlled by Yak1, Rim15 and Mck1, and the three kinases mediate the TOR1-regulated accumulation of storage carbohydrates and CLS extension. Our data support the hypothesis that metabolic reprogramming to accumulate energy stores and the activation of anti-oxidant defence systems are coordinated by Yak1, Rim15 and Mck1 kinases to ensure quiescence entry and lifespan extension in yeast. PMID:27923067

Composition of Dietary Fat Source Shapes Gut Microbiota Architecture and Alters Host Inflammatory Mediators in Mouse Adipose Tissue

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Huang, Edmond; Leone, Vanessa; Devkota, Suzanne; Wang, Yunwei; Brady, Matthew; Chang, Eugene

2013-01-01

Background Growing evidence shows that dietary factors can dramatically alter the gut microbiome in ways that contribute to metabolic disturbance and progression of obesity. In this regard, mesenteric adipose tissue has been implicated in mediating these processes through the elaboration of pro-inflammatory adipokines. In this study, we examined the relationship of these events by determining the effects of dietary fat content and source on gut microbiota, as well as the effects on adipokine profiles of mesenteric and peripheral adipocytes. Methods Adult male C57Bl/6 mice were fed milk fat-, lard-(SFA sources), or safflower oil (PUFA)- based high fat diets for four weeks. Body mass and food consumption were measured. Stool 16S rRNA was isolated and analyzed via T-RFLP as well as variable V3-4 sequence tags via next gen sequencing. Mesenteric and gonadal adipose samples were analyzed for both lipogenic and inflammatory mediators via qRT-PCR. Results High-fat feedings caused more weight gain with concomitant increases in caloric consumption relative to low-fat diets. Additionally, each of the high fat diets induced dramatic and specific 16S rRNA phylogenic profiles that were associated with different inflammatory and lipogenic mediator profile of mesenteric and gonadal fat depots. Conclusions Our findings support the notion that dietary fat composition can both reshape the gut microbiota as well as alter host adipose tissue inflammatory/lipogenic profiles. They also demonstrate the interdependency of dietary fat source, commensal gut microbiota, and inflammatory profile of mesenteric fat that can collectively impact the host metabolic state. PMID:23639897

Magpies and mirrors : identity as a mediator of music preferences across the lifespan

OpenAIRE

Leadbeater, Richard; Marsden, Alan

2014-01-01

This thesis examines the role of identity on the development and trajectory of music preferences across the lifespan. The focus of interest in recent empirical research has been to predict music preferences using adolescent individual differences. It is widely recognized that adolescents use music to help them deal with a number of psychosocial and emotional challenges, which often arise during this critical period of identity development. There has been little study whether adults similarly ...

No impact of dietary iodine restriction in short term development of hypothyroidism following fixed dose radioactive iodine therapy for Graves' disease.

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Jacob, Jubbin Jagan; Stephen, Charles; Paul, Thomas V; Thomas, Nihal; Oommen, Regi; Seshadri, Mandalam S

2015-01-01

The increased incidence of autoimmune thyroid disease with increasing dietary iodine intake has been demonstrated both epidemiologically and experimentally. The hypothyroidism that occurs in the first year following radioactive iodine therapy is probably related to the destructive effects of the radiation and underlying ongoing autoimmunity. To study the outcomes at the end of six months after fixed dose I, (131)therapy for Graves' disease followed by an iodine restricted diet for a period of six months. Consecutive adult patients with Graves' disease planned for I(131) therapy were randomized either to receive instructions regarding dietary iodine restriction or no advice prior to fixed dose (5mCi) I(131) administration. Thyroid functions and urinary iodine indices were evaluated at 3(rd) and 6(th) month subsequently. Forty seven patients (13M and 34F) were assessed, 2 were excluded, 45 were randomized (Cases 24 and Controls 21) and 39 patients completed the study. Baseline data was comparable. Median urinary iodine concentration was 115 and 273 μg/gm creat (p = 0.00) among cases and controls respectively. Outcomes at the 3(rd) month were as follows (cases and controls); Euthyroid (10 and 6: P = 0.24), Hypothyroid (3 and 5: P = 0.38) and Hyperthyroid (7 and 8: P = 0.64). Outcomes at the end of six months were as follows (cases and controls); Euthyroid (10 and 5: P = 0.12), Hypothyroid (3 and 5: P = 0.38) and Hyperthyroid (7 and 9: P = 0.43). Of the hypothyroid patients 5 (cases 1 and controls 4: P = 0.13) required thyroxine replacement. There was no statistical significant difference in the outcome of patients with dietary iodine restriction following I(131) therapy for Graves' disease.

Effects of dietary selenium supply and timing of nutrient restriction during gestation on maternal growth and body composition of pregnant adolescent ewes.

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Carlson, D B; Reed, J J; Borowicz, P P; Taylor, J B; Reynolds, L P; Neville, T L; Redmer, D A; Vonnahme, K A; Caton, J S

2009-02-01

The objectives were to examine effects of dietary Se supplementation and nutrient restriction during defined periods of gestation on maternal adaptations to pregnancy in primigravid sheep. Sixty-four pregnant Western Whiteface ewe lambs were assigned to treatments in a 2 x 4 factorial design. Treatments were dietary Se [adequate Se (ASe; 3.05 microg/kg of BW) vs. high Se (HSe; 70.4 microg/kg of BW)] fed as Se-enriched yeast, and plane of nutrition [control (C; 100% of NRC requirements) vs. restricted (R; 60% of NRC requirements]. Selenium treatments were fed throughout gestation. Plane of nutrition treatments were applied during mid (d 50 to 90) and late gestation (d 90 to 130), which resulted in 4 distinct plane of nutrition treatments [treatment: CC (control from d 50 to 130), RC (restricted from d 50 to 90, and control d 90 to 130), CR (control from d 50 to 90, and restricted from d 90 to 130), and RR (restricted from d 50 to 130)]. All of the pregnant ewes were necropsied on d 132 +/- 0.9 of gestation (length of gestation approximately 145 d). Nutrient restriction treatments decreased ewe ADG and G:F, as a result, RC and CR ewes had similar BW and maternal BW (MBW) at necropsy, whereas RR ewes were lighter than RC and CR ewes. From d 90 to 130, the HSe-CC ewes had greater ADG (Se x nutrition; P = 0.05) than did ASe-CC ewes, whereas ADG and G:F (Se x nutrition; P = 0.08) were less for HSe-RR ewes compared with ASe-RR ewes. The CR and RR treatments decreased total gravid uterus weight (P = 0.01) as well as fetal weight (P = 0.02) compared with RC and CC. High Se decreased total (g; P = 0.09) and relative heart mass (g/kg of MBW; P = 0.10), but increased total and relative mass of liver (P RC. Total small intestine mass was similar between RC and CC ewes, but was markedly reduced (P RC than for CR ewes. Increased Se decreased jejunal DNA concentration (P = 0.07), total jejunal cell number (P = 0.03), and total proliferating jejunal cell number (P = 0.05) compared

Calycosin promotes lifespan in Caenorhabditis elegans through insulin signaling pathway via daf-16, age-1 and daf-2.

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Lu, Lulu; Zhao, Xuan; Zhang, Jianyong; Li, Miao; Qi, Yonghao; Zhou, Lijun

2017-07-01

The naturally occurring calycosin is a known antioxidant that prevents redox imbalance in organisms. However, calycosin's effect on lifespan and its physiological molecular mechanisms are not yet well understood. In this study, we demonstrated that calycosin could prolong the lifespan of Caenorhabditis elegans, and that such extension was associated with its antioxidant capability as well as its ability to enhance stress resistance and reduce ROS (reactive oxygen species) accumulation. To explore mechanisms of this longevity effect, we assessed the impact of calycosin on lifespans of insulin-signaling impaired worms: daf-2, age-1, and daf-16 mutants. We found that calycosin did not alter the lifespan of all three mutants, thereby suggesting that calycosin requires insulin signaling to promote lifespan extension. On the other hand, we observed that calycosin could enhance the nuclear translocation of the core transcription factor DAF-16/FoXO instead of the conserved stress-responsive transcription factor SKN-1/Nrf-2. This observation is consistent with the understanding that the nuclear localized DAF-16 up-regulates its downstream targets sod-3, ctl-1, and hsp-16.2. Lastly, it is also noteworthy that the longevity effect of calycosin is likely not associated with the calorie restriction mechanism. Collectively, our results strongly suggest that calycosin could function as an antioxidant to extend the lifespan of C. elegans by enhancing nucleus translocation of DAF-16 through the insulin-signaling pathway. Copyright © 2017 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

Effect of dietary restriction and subsequent re-alimentation on the transcriptional profile of bovine ruminal epithelium.

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Kate Keogh

Full Text Available Compensatory growth (CG is utilised worldwide in beef production systems as a management approach to reduce feed costs. However the underlying biology regulating the expression of CG remains to be fully elucidated. The objective of this study was to examine the effect of dietary restriction and subsequent re-alimentation induced CG on the global gene expression profile of ruminal epithelial papillae. Holstein Friesian bulls (n = 60 were assigned to one of two groups: restricted feed allowance (RES; n = 30 for 125 days (Period 1 followed by ad libitum access to feed for 55 days (Period 2 or (ii ad libitum access to feed throughout (ADLIB; n = 30. At the end of each period, 15 animals from each treatment were slaughtered and rumen papillae harvested. mRNA was isolated from all papillae samples collected. cDNA libraries were then prepared and sequenced. Resultant reads were subsequently analysed bioinformatically and differentially expressed genes (DEGs are defined as having a Benjamini-Hochberg P value of <0.05. During re-alimentation in Period 2, RES animals displayed CG, growing at 1.8 times the rate of their ADLIB contemporary animals in Period 2 (P < 0.001. At the end of Period 1, 64 DEGs were identified between RES and ADLIB, with only one DEG identified at the end of Period 2. When analysed within RES treatment (RES, Period 2 v Period 1, 411 DEGs were evident. Genes identified as differentially expressed in response to both dietary restriction and subsequent CG included those involved in processes such as cellular interactions and transport, protein folding and gene expression, as well as immune response. This study provides an insight into the molecular mechanisms underlying the expression of CG in rumen papillae of cattle; however the results suggest that the role of the ruminal epithelium in supporting overall animal CG may have declined by day 55 of re-alimentation.

Effect of dietary restriction on metabolic, anatomic and molecular traits in mice depends on the initial level of basal metabolic rate.

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Brzek, Pawel; Ksiazek, Aneta; Dobrzyn, Agnieszka; Konarzewski, Marek

2012-09-15

Dietary restriction (DR)-related delay of ageing is hypothesized to be mediated by the reduction of the metabolic rate (MR). However, studies on the effect of DR on MR have produced equivocal results. We demonstrated that this lack of congruency can be due to a variation in the initial level of MR within a given pool of experimental subjects. We subjected laboratory mice from two line types divergently selected for basal MR (BMR) to 30% DR lasting 6 months to test whether the effect of DR depends on the initial variation in BMR and peak MR. BMR and peak MR were independently affected by DR. The effect of DR was stronger in line types with higher initial levels of MR. Line-type-specific changes in the proportions of body components explained contrasting effects of DR on the mass-corrected BMR, which decreased in the high-BMR line type and did not change in the low-BMR line type. We conclude that the initial variation in MR can significantly affect response to DR. However, we found no association between the level of MR and mechanisms underlying the susceptibility to or protection against oxidative stress.

Caloric restriction and intermittent fasting: Two potential diets for successful brain aging

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Martin, Bronwen; Mattson, Mark P.; Maudsley, Stuart

2008-01-01

The vulnerability of the nervous system to advancing age is all too often manifest in neurodegenerative disorders such as Alzheimer's and Parkinson's diseases. In this review article we describe evidence suggesting that two dietary interventions, caloric restriction (CR) and intermittent fasting (IF), can prolong the health-span of the nervous system by impinging upon fundamental metabolic and cellular signaling pathways that regulate life-span. CR and IF affect energy and oxygen radical metabolism, and cellular stress response systems, in ways that protect neurons against genetic and environmental factors to which they would otherwise succumb during aging. There are multiple interactive pathways and molecular mechanisms by which CR and IF benefit neurons including those involving insulin-like signaling, FoxO transcription factors, sirtuins and peroxisome proliferator-activated receptors. These pathways stimulate the production of protein chaperones, neurotrophic factors and antioxidant enzymes, all of which help cells cope with stress and resist disease. A better understanding of the impact of CR and IF on the aging nervous system will likely lead to novel approaches for preventing and treating neurodegenerative disorders. PMID:16899414

Weight loss in obese men by caloric restriction and high-dose diazoxide-mediated insulin suppression.

NARCIS (Netherlands)

Boekel, G.A.J van; Loves, S.; Sorge, A.A. van; Ruinemans-Koerts, J.; Rijnders, T.; Boer, H. de

2008-01-01

OBJECTIVE: To examine the concept whether high-dose diazoxide (DZX)-mediated insulin suppression, in combination with moderate caloric restriction and increased physical activity, can establish a weight loss of at least 15% in obese hyperinsulinaemic men. DESIGN: Open, uncontrolled, 6-month pilot

Effect of dietary restriction and subsequent re-alimentation on the transcriptional profile of hepatic tissue in cattle.

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Keogh, Kate; Kenny, David A; Cormican, Paul; Kelly, Alan K; Waters, Sinead M

2016-03-17

Compensatory growth (CG) is an accelerated growth phenomenon observed in animals upon re-alimentation following a period of dietary restriction. It is typically utilised in livestock systems to reduce feed costs during periods of reduced feed availability. The biochemical mechanisms controlling this phenomenon, however, are yet to be elucidated. This study aimed to uncover the molecular mechanisms regulating the hepatic expression of CG in cattle, utilising RNAseq. RNAseq was performed on hepatic tissue of bulls following 125 days of dietary restriction (RES) and again following 55 days of subsequent re-alimentation during which the animals exhibited significant CG. The data were compared with those of control animals offered the same diet on an ad libitum basis throughout (ADLIB). Elucidation of the molecular control of CG may yield critical information on genes and pathways which could be targeted as putative molecular biomarkers for the selection of animals with improved CG potential. Following a period of differential feeding, body-weight and liver weight were 161 and 4 kg higher, respectively, for ADLIB compared with RES animals. At this time RNAseq analysis of liver tissue revealed 1352 significantly differentially expressed genes (DEG) between the two treatments. DEGs indicated down-regulation of processes including nutrient transport, cell division and proliferation in RES. In addition, protein synthesis genes were up-regulated in RES following a period of restricted feeding. The subsequent 55 days of ad libitum feeding for both groups resulted in the body-weight difference reduced to 84 kg, with no difference in liver weight between treatment groups. At the end of 55 days of unrestricted feeding, 49 genes were differentially expressed between animals undergoing CG and their continuously fed counterparts. In particular, hepatic expression of cell proliferation and growth genes were greater in animals undergoing CG. Greater expression of cell cycle and cell

Lifespan extension and increased resistance to environmental stressors by N-Acetyl-L-Cysteine in Caenorhabditis elegans

Directory of Open Access Journals (Sweden)

Seung-Il Oh

2015-05-01

Full Text Available OBJECTIVE: This study was performed to determine the effect of N-acetyl-L-cysteine, a modified sulfur-containing amino acid that acts as a strong cellular antioxidant, on the response to environmental stressors and on aging in C. elegans. METHOD: The survival of worms under oxidative stress conditions induced by paraquat was evaluated with and without in vivo N-acetyl-L-cysteine treatment. The effect of N-acetyl-L-cysteine on the response to other environmental stressors, including heat stress and ultraviolet irradiation (UV, was also monitored. To investigate the effect on aging, we examined changes in lifespan, fertility, and expression of age-related biomarkers in C. elegans after N-acetyl-L-cysteine treatment. RESULTS: Dietary N-acetyl-L-cysteine supplementation significantly increased resistance to oxidative stress, heat stress, and UV irradiation in C. elegans. In addition, N-acetyl-L-cysteine supplementation significantly extended both the mean and maximum lifespan of C. elegans. The mean lifespan was extended by up to 30.5% with 5 mM N-acetyl-L-cysteine treatment, and the maximum lifespan was increased by 8 days. N-acetyl-L-cysteine supplementation also increased the total number of progeny produced and extended the gravid period of C. elegans. The green fluorescent protein reporter assay revealed that expression of the stress-responsive genes, sod-3 and hsp-16.2, increased significantly following N-acetyl-L-cysteine treatment. CONCLUSION: N-acetyl-L-cysteine supplementation confers a longevity phenotype in C. elegans, possibly through increased resistance to environmental stressors.

Dietary Methionine Restriction Alleviates Hyperglycemia in Pigs with Intrauterine Growth Restriction by Enhancing Hepatic Protein Kinase B Signaling and Glycogen Synthesis.

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Ying, Zhixiong; Zhang, Hao; Su, Weipeng; Zhou, Le; Wang, Fei; Li, Yue; Zhang, Lili; Wang, Tian

2017-10-01

Background: Individuals with intrauterine growth restriction (IUGR) are prone to developing type 2 diabetes mellitus (T2DM). Dietary methionine restriction (MR) improves insulin sensitivity and glucose homeostasis in individuals with normal birth weight (NBW). Objective: This study investigated the effects of MR on plasma glucose concentration and hepatic and muscle glucose metabolism in pigs with IUGR. Methods: Thirty female NBW and 60 same-sex spontaneous IUGR piglets (Landrace × Yorkshire) were selected. After weaning (day 21), the piglets were fed diets with adequate methionine (NBW-CON and IUGR-CON) or 30% less methionine (IUGR-MR) ( n = 6). At day 180, 1 pig with a body weight near the mean of each replication was selected for biochemical analysis. Results: The IUGR-CON group showed 41.6%, 68.6%, and 67.1% higher plasma glucose concentration, hepatic phosphoenolpyruvate carboxykinase activity, and glucose-6-phosphatase activity, respectively, than the NBW-CON group ( P glycogen content and glycogen synthase activity were 36.9% and 38.8% lower, respectively, in the IUGR-CON than the NBW-CON group ( P glycogen content and glycogen synthase activity of the IUGR-MR pigs were 62.9% and 50.8% higher than those of the IUGR-CON pigs ( P glycogen synthesis, implying a potential nutritional strategy to prevent type 2 diabetes mellitus in IUGR offspring. © 2017 American Society for Nutrition.

Metabolic Regulation of Methionine Restriction in Diabetes.

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Yin, Jie; Ren, Wenkai; Chen, Shuai; Li, Yuying; Han, Hui; Gao, Jing; Liu, Gang; Wu, Xin; Li, Tiejun; Kim, Sung Woo; Yin, Yulong

2018-03-30

Although the effects of dietary methionine restriction have been investigated in the physiology of aging and diseases related to oxidative stress, the relationship between methionine restriction and the development of metabolic disorders has not been explored extensively. This review summarizes studies of the possible involvement of dietary methionine restriction in improving insulin resistance, glucose homeostasis, oxidative stress, lipid metabolism, the pentose phosphate pathway, and inflammation, with an emphasis on the fibroblast growth factor 21 and protein phosphatase 2A signals and autophagy in diabetes. Diets deficient in methionine may be a useful nutritional strategy in patients with diabetes. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Lower Doses of Fructose Extend Lifespan in Caenorhabditis elegans.

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Zheng, Jolene; Gao, Chenfei; Wang, Mingming; Tran, Phuongmai; Mai, Nancy; Finley, John W; Heymsfield, Steven B; Greenway, Frank L; Li, Zhaoping; Heber, David; Burton, Jeffrey H; Johnson, William D; Laine, Roger A

2017-05-04

Epidemiological studies indicate that the increased consumption of sugars including sucrose and fructose in beverages correlate with the prevalence of obesity, type-2 diabetes, insulin resistance, hyperinsulinemia, hypertriglyceridemia, and hypertension in humans. A few reports suggest that fructose extends lifespan in Saccharomyces cerevisiae. In Anopheles gambiae, fructose, glucose, or glucose plus fructose also extended lifespan. New results presented here suggest that fructose extends lifespan in Caenorhabditis elegans (C. elegans) wild type (N2). C. elegans were fed standard laboratory food source (E. coli OP50), maintained in liquid culture. Experimental groups received additional glucose (111 mM), fructose (55 mM, 111 mM, or 555 mM), sucrose (55 mM, 111 mM, or 555 mM), glucose (167 mM) plus fructose (167 mM) (G&F), or high fructose corn syrup (HFCS, 333 mM). In four replicate experiments, fructose dose-dependently increased mean lifespan at 55 mM or 111 m Min N2, but decreased lifespan at 555 mM (P Glucose reduced lifespan (P fructose (555 mM), glucose (111 mM), and sucrose (55 mM, 111 mM, and 555 mM). Here we report a biphasic effect of fructose increasing lifespan at lower doses and shortening lifespan at higher doses with an inverse effect on IFD. In view of reports that fructose increases lifespan in yeast, mosquitoes and now nematodes, while decreasing fat deposition (in nematodes) at lower concentrations, further research into the relationship of fructose to lifespan and fat accumulation in vertebrates and mammals is indicated.

Effects of long-term heat stress and dietary restriction on the expression of genes of steroidogenic pathway and small heat-shock proteins in rat testicular tissue.

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Bozkaya, F; Atli, M O; Guzeloglu, A; Kayis, S A; Yildirim, M E; Kurar, E; Yilmaz, R; Aydilek, N

2017-08-01

The aim was to investigate the effects of long-term heat stress and dietary restriction on the expression of certain genes involving in steroidogenic pathway and small heat-shock proteins (sHSPs) in rat testis. Sprague Dawley rats (n = 24) were equally divided into four groups. Group I and II were kept at an ambient temperature of 22°C, while Groups III and IV were reared at 38°C for 9 weeks. Feed was freely available for Group I and Group III, while Group II and Group IV were fed 60% of the diet consumed by their ad libitum counterparts. At the end of 9 weeks, testicles were collected under euthanasia. Total RNA was isolated from testis tissue samples. Expression profiles of the genes encoding androgen-binding protein, follicle-stimulating hormone receptor, androgen receptor, luteinising hormone receptor, steroidogenic acute regulatory protein (StAR), cyclooxygenase-2 and sHSP genes were assessed at mRNA levels using qPCR. Long-term heat stress decreased the expression of StAR and HspB10 genes while dietary restriction upregulated StAR gene expression. The results suggested that long-term heat stress negatively affected the expression of StAR and HspB10 genes and the dietary restriction was able to reverse negative effect of heat stress on the expression of StAR gene in rat testis. © 2016 Blackwell Verlag GmbH.

An engineering approach to extending lifespan in C. elegans.

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Dror Sagi

Full Text Available We have taken an engineering approach to extending the lifespan of Caenorhabditis elegans. Aging stands out as a complex trait, because events that occur in old animals are not under strong natural selection. As a result, lifespan can be lengthened rationally using bioengineering to modulate gene expression or to add exogenous components. Here, we engineered longer lifespan by expressing genes from zebrafish encoding molecular functions not normally present in worms. Additionally, we extended lifespan by increasing the activity of four endogenous worm aging pathways. Next, we used a modular approach to extend lifespan by combining components. Finally, we used cell- and worm-based assays to analyze changes in cell physiology and as a rapid means to evaluate whether multi-component transgenic lines were likely to have extended longevity. Using engineering to add novel functions and to tune endogenous functions provides a new framework for lifespan extension that goes beyond the constraints of the worm genome.

SIRT1 stimulation by polyphenols is affected by their stability and metabolism

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Boer, de V.C.J.; Goffau, de L.; Arts, I.C.W.; Hollman, P.C.H.; Keijer, J.

2006-01-01

Silent information regulator two ortholog 1 (SIRT1) is the human ortholog of the yeast sir2 protein; one of the most important regulators of lifespan extension by caloric restriction in several organisms. Dietary polyphenols, abundant in vegetables, fruits, cereals, wine and tea, were reported to

Dietary restraint partially mediates the relationship between impulsivity and binge eating only in lean individuals: The importance of accounting for body mass in studies of restraint

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Jaime Ashley Coffino

2016-10-01

Full Text Available Binge eating is characteristic of eating and weight-related disorders such as binge eating disorder, bulimia nervosa, and obesity. In light of data that suggests impulsivity is associated with overeating specifically in restrained eaters, this study sought to elucidate the exact nature of the associations between these variables, hypothesizing that the relationship between impulsivity and binge eating is mediated by restrained eating. We further hypothesized that the role of dietary restraint as a mediator would be moderated by body mass index (BMI. Study participants (n = 506, 50.6% female were categorized based on self-reported BMI as under- and normal weight (BMI < 25, 65.8%, n = 333 or overweight and obese (BMI ≥ 25, 34.2%, n = 173 and completed the restrained eating subscale of the Dutch Eating Behavior Questionnaire, the difficulties with impulse control subscale of the Difficulties with Emotion Regulation Scale, and the Binge Eating Scale. Findings provide initial evidence for the hypothesized moderated mediation model, with dietary restraint partially mediating the relationship between impulsivity and binge eating severity only in lean respondents. In respondents with overweight or obesity, impulsivity was significantly correlated with binge eating severity, but dietary restraint was not. Findings inform our conceptualization of dietary restraint as a possible risk factor for binge eating and highlight the importance of accounting for body mass in research on the impact of dietary restraint on eating behaviors.

Effect of dietary restriction on immune response of laboratory mice divergently selected for basal metabolic rate.

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Książek, Aneta; Konarzewski, Marek

2012-01-01

To study whether dietary restriction (DR; 70% of ad lib. feeding)-elicited immunosuppression results from the trade-off between the costs of mounting an immune response and the metabolic costs of maintenance, we subjected mice from two divergent lines selected for high basal metabolic rate (H-BMR) and low BMR (L-BMR) to 4 wk of DR and then challenged them with keyhole limpet hemocyanin (KLH) antigen. Those line types differ genetically with respect to BMR and to the mass of metabolically expensive internal organs, which are larger in H-BMR mice. In mice of both line types, DR resulted in a significant reduction of body mass, an immune response, and the downsizing of spleen, lymph nodes, thymus, heart, and kidneys but not small intestines. DR resulted in a greater reduction of the spleen and lymph nodes in mice of the H-BMR line type, whereas the thymus was more affected in L-BMR line type. In contrast, immunization resulted in an increase of liver mass in DR mice of both line types. A comparison of the results of current and earlier studies on the same mouse line types suggests that metabolic trade-offs involving the costs of an immune response are more apparent when animals are forced to increase energy demands (e.g., by cold exposure) compared to when energy demands are decreased through DR. Our findings also suggest that divelrgent selection on BMR resulted in between-line-type differences in T-cell- and B-cell-mediated types of an immune response. More generally, our results indicate that production of a wide repertoire of antibodies is not correlated with high BMR.

Minority Stress across the Career-Lifespan Trajectory

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Dispenza, Franco; Brown, Colton; Chastain, Taylor E.

2016-01-01

Sexual minority persons (e.g., lesbian, gay, bisexual, and queer) are likely to encounter "minority stress", such as discrimination, concealment, expectation of rejection, and internalized heterosexism. Minority stress occurs alongside one's lifespan and has considerable implications in the context of the career lifespan trajectory.…

Mitobolites: the elixir of life.

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Katewa, Subhash D; Khanna, Amit; Kapahi, Pankaj

2014-07-01

One of the biggest challenges in biology is to understand how mitochondria influence aging and age-related diseases. Chin et al. (2014) reveal how a mitochondrial metabolite (mitobolite) inhibits mitochondrial ATPase and extends lifespan by mimicking dietary restriction in worms. Copyright © 2014 Elsevier Inc. All rights reserved.

Effects of Dietary Restriction on the Expression of Lipid Metabolism and Growth Hormone Signaling Genes in the Muscle of Korean Cattle Steers

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H. J. Kang

2015-08-01

Full Text Available This study determined the effects of dietary restriction on growth and the expression of lipid metabolism and growth hormone signaling genes in the longissimus dorsi muscle (LM of Korean cattle. Thirty-one Korean cattle steers (average age 10.5 months were allocated to normal (N; n = 16 or dietary restriction (DR; n = 15 groups. The feeding trial consisted of two stages: for the 8-month growing period, the DR group was fed 80% of the food intake of the normal diet, and for the 6-month growth-finishing period, the DR group was fed a DR total mixed ration with 78.4% of the crude protein and 64% of the net energy for gain of the normal diet. The LM was biopsied 5 months (period 1 [P1] at 15.5 months of age and 14 months (period 2 [P2] at 24.5 months of age after the start of feeding. The mRNA levels were determined using real-time polymerase chain reaction. Body weight, daily feed intake, average daily gain, and feed efficiency were lower in the DR group compared with the normal group at both P1 and P2. At P1, the lipogenic fatty acid synthase (FASN mRNA levels were lower (p<0.05 in the DR group compared with the normal group. The DR group tended (p = 0.06 to have higher of levels of growth hormone receptor (GHR mRNA than the normal group. At P2, the DR group tended to have lower (p = 0.06 androgen receptor (AR mRNA levels than the normal group. In conclusion, our results demonstrate that dietary restriction partially decreases the transcription of lipogenic FASN and growth hormone signaling AR genes, but increases transcription of the GHR gene. These changes in gene transcription might affect body fat accumulation and the growth of the animals.

Nutrigenetics and nutrigenomics of caloric restriction.

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Abete, Itziar; Navas-Carretero, Santiago; Marti, Amelia; Martinez, J Alfredo

2012-01-01

Obesity is a complex disease resulting from a chronic and long-term positive energy balance in which both genetic and environmental factors are involved. Weight-reduction methods are mainly focused on dietary changes and increased physical activity. However, responses to nutritional intervention programs show a wide range of interindividual variation, which is importantly influenced by genetic determinants. In this sense, subjects carrying several obesity-related single-nucleotide polymorphisms (SNPs) show differences in the response to calorie-restriction programs. Furthermore, there is evidence indicating that dietary components not only fuel the body but also participate in the modulation of gene expression. Thus, the expression pattern and nutritional regulation of several obesity-related genes have been studied, as well as those that are differentially expressed by caloric restriction. The responses to caloric restriction linked to the presence of SNPs in obesity-related genes are reviewed in this chapter. Also, the influence of energy restriction on gene expression pattern in different tissues is addressed. Copyright © 2012 Elsevier Inc. All rights reserved.

Effect of chlorella and its fractions on blood pressure, cerebral stroke lesions, and life-span in stroke-prone spontaneously hypertensive rats.

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Sansawa, Hiroshi; Takahashi, Masatoshi; Tsuchikura, Satoru; Endo, Hiroshi

2006-12-01

Effects of Chlorella regularis (dried cell powder)--cultured axenically under heterotrophic conditions, and provided as a dietary supplement--and its fractions on the blood pressure, cerebral stroke lesions, and life-span of stroke-prone spontaneously hypertensive rats (SHRSP/Izm) were investigated. When SHRSP were fed on diets with supplemented Chlorella to a commercial diet (Funabashi SP), elevation of blood pressure was significantly lower in the Chlorella groups than in the control group. At 21 wk of feeding, serum total cholesterol was significantly lower in the Chlorella groups than in the control group. Histopathological examination revealed cerebral vascular accidents in the brains of the control group, but those of Chlorella groups showed apparently low incidence compared to the control group. The average life-span of the Chlorella groups were significantly longer than that of the control group (p vascular function of rats.

Effect of dietary restriction and subsequent re-alimentation on the transcriptional profile of bovine ruminal epithelium.

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Keogh, Kate; Waters, Sinead M; Cormican, Paul; Kelly, Alan K; O'Shea, Emma; Kenny, David A

2017-01-01

Compensatory growth (CG) is utilised worldwide in beef production systems as a management approach to reduce feed costs. However the underlying biology regulating the expression of CG remains to be fully elucidated. The objective of this study was to examine the effect of dietary restriction and subsequent re-alimentation induced CG on the global gene expression profile of ruminal epithelial papillae. Holstein Friesian bulls (n = 60) were assigned to one of two groups: restricted feed allowance (RES; n = 30) for 125 days (Period 1) followed by ad libitum access to feed for 55 days (Period 2) or (ii) ad libitum access to feed throughout (ADLIB; n = 30). At the end of each period, 15 animals from each treatment were slaughtered and rumen papillae harvested. mRNA was isolated from all papillae samples collected. cDNA libraries were then prepared and sequenced. Resultant reads were subsequently analysed bioinformatically and differentially expressed genes (DEGs) are defined as having a Benjamini-Hochberg P value of alimentation in Period 2, RES animals displayed CG, growing at 1.8 times the rate of their ADLIB contemporary animals in Period 2 (P alimentation.

SirT1 regulates energy metabolism and response to caloric restriction in mice.

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Gino Boily

Full Text Available The yeast sir2 gene and its orthologues in Drosophila and C. elegans have well-established roles in lifespan determination and response to caloric restriction. We have studied mice carrying two null alleles for SirT1, the mammalian orthologue of sir2, and found that these animals inefficiently utilize ingested food. These mice are hypermetabolic, contain inefficient liver mitochondria, and have elevated rates of lipid oxidation. When challenged with a 40% reduction in caloric intake, normal mice maintained their metabolic rate and increased their physical activity while the metabolic rate of SirT1-null mice dropped and their activity did not increase. Moreover, CR did not extend lifespan of SirT1-null mice. Thus, SirT1 is an important regulator of energy metabolism and, like its orthologues from simpler eukaryotes, the SirT1 protein appears to be required for a normal response to caloric restriction.

A Motivational Theory of Life-Span Development

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Heckhausen, Jutta; Wrosch, Carsten; Schulz, Richard

2010-01-01

This article had four goals. First, the authors identified a set of general challenges and questions that a life-span theory of development should address. Second, they presented a comprehensive account of their Motivational Theory of Life-Span Development. They integrated the model of optimization in primary and secondary control and the…

The mediating and moderating role of planning on mothers' decisions for early childhood dietary behaviours.

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Hamilton, Kyra; Kothe, Emily J; Mullan, Barbara; Spinks, Teagan

2017-12-01

Examine the roles of action and coping planning on the intention-behaviour relationship for mothers' decisions for their young children's dietary behaviours. Prospective design with two waves of data collection, one week apart. Mothers (N = 197, M age  = 34.39, SD = 5.65) of children aged 2-3 years completed a main questionnaire assessing planning constructs and intentions, and a one-week follow-up of the target behaviours - 'healthy eating' and 'discretionary choices'. Intention was the strongest predictor of behaviour for both dietary behaviours. For healthy eating, intention moderated the indirect relationship between intention-behaviour via planning; coping planning was less important when intention was strong. Further, intention was not a direct predictor of behaviour when intention was relatively low. Action planning was not a direct predictor of either behaviour after accounting for intention and coping planning; action planning on behaviour was mediated by coping planning (only for healthy eating). Intention was not a direct predictor of coping planning; intention on coping planning was mediated by action planning. Neither type of planning predicted discretionary choices. Current findings contribute novel information on the mechanisms underpinning the effect of action and coping planning on the intention-behaviour relationship.

Sex-specific lifespan and its evolution in nematodes.

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Ancell, Henry; Pires-daSilva, Andre

2017-10-01

Differences between sexes of the same species in lifespan and aging rate are widespread. While the proximal and evolutionary causes of aging are well researched, the factors that contribute to sex differences in these traits have been less studied. The striking diversity of nematodes provides ample opportunity to study variation in sex-specific lifespan patterns associated with shifts in life history and mating strategy. Although the plasticity of these sex differences will make it challenging to generalize from invertebrate to vertebrate systems, studies in nematodes have enabled empirical evaluation of predictions regarding the evolution of lifespan. These studies have highlighted how natural and sexual selection can generate divergent patterns of lifespan if the sexes are subject to different rates or sources of mortality, or if trade-offs between complex traits and longevity are resolved differently in each sex. Here, we integrate evidence derived mainly from nematodes that addresses the molecular and evolutionary basis of sex-specific aging and lifespan. Ultimately, we hope to generate a clearer picture of current knowledge in this area, and also highlight the limitations of our understanding. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

The Growth Hormone Receptor Gene-Disrupted (GHR-KO) Mouse Fails to Respond to an Intermittent Fasting (IF) Diet

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Arum, Oge; Bonkowski, Michael S.; Rocha, Juliana S.; Bartke, Andrzej

2009-01-01

SUMMARY The interaction of longevity-conferring genes with longevity-conferring diets is poorly understood. The growth hormone receptor gene-disrupted (GHR-KO) mouse is long-lived; and this longevity is not responsive to 30% caloric restriction (CR), in contrast to wild-type animals from the same strain. To determine whether this may have been limited to a particular level of dietary restriction (DR), we subjected GHR-KO mice to a different dietary restriction regimen, an intermittent fasting (IF) diet. The IF diet increased the survivorship and improved insulin sensitivity of normal males, but failed to affect either parameter in GHR-KO mice. From the results of two paradigms of dietary restriction we postulate that GHR-KO mice would be resistant to any manner of DR; potentially due to their inability to further enhance insulin sensitivity. Insulin sensitivity may be a mechanism and/or a marker of the lifespan-extending potential of an intervention. PMID:19747233

AgeFactDB—the JenAge Ageing Factor Database—towards data integration in ageing research

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Hühne, Rolf; Thalheim, Torsten; Sühnel, Jürgen

2014-01-01

AgeFactDB (http://agefactdb.jenage.de) is a database aimed at the collection and integration of ageing phenotype data including lifespan information. Ageing factors are considered to be genes, chemical compounds or other factors such as dietary restriction, whose action results in a changed lifespan or another ageing phenotype. Any information related to the effects of ageing factors is called an observation and is presented on observation pages. To provide concise access to the complete information for a particular ageing factor, corresponding observations are also summarized on ageing factor pages. In a first step, ageing-related data were primarily taken from existing databases such as the Ageing Gene Database—GenAge, the Lifespan Observations Database and the Dietary Restriction Gene Database—GenDR. In addition, we have started to include new ageing-related information. Based on homology data taken from the HomoloGene Database, AgeFactDB also provides observation and ageing factor pages of genes that are homologous to known ageing-related genes. These homologues are considered as candidate or putative ageing-related genes. AgeFactDB offers a variety of search and browse options, and also allows the download of ageing factor or observation lists in TSV, CSV and XML formats. PMID:24217911

Role of Protein Synthesis Initiation Factors in Dietary Soy Isoflavone-Mediated Effects on Breast Cancer Progression

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2012-03-01

Manuscript s • Submitted to the Journal of Nutritional Biochemistry (Feb 21, 2012) “The soy isoflavone equol may increase cancer malignancy via upregulation...29] Ko KP, Park SK, Park B et al. Isoflavones from phytoestrogens and gastric cancer risk: a nested case-control study within the Korean...Dietary Soy Isoflavone-Mediated Effects on Breast Cancer Progression. PRINCIPAL INVESTIGATOR: Columba de la Parra Simental CONTRACTING

Effects of dietary fat energy restriction and fish oil feeding on hepatic metabolic abnormalities and insulin resistance in KK mice with high-fat diet-induced obesity.

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Arai, Takeshi; Kim, Hyoun-ju; Hirako, Satoshi; Nakasatomi, Maki; Chiba, Hiroshige; Matsumoto, Akiyo

2013-01-01

We investigated the effects of dietary fat energy restriction and fish oil intake on glucose and lipid metabolism in female KK mice with high-fat (HF) diet-induced obesity. Mice were fed a lard/safflower oil (LSO50) diet consisting of 50 energy% (en%) lard/safflower oil as the fat source for 12 weeks. Then, the mice were fed various fat energy restriction (25 en% fat) diets - LSO, FO2.5, FO12.5 or FO25 - containing 0, 2.5, 12.5, or 25 en% fish oil, respectively, for 9 weeks. Conversion from a HF diet to each fat energy restriction diet significantly decreased final body weights and visceral and subcutaneous fat mass in all fat energy restriction groups, regardless of fish oil contents. Hepatic triglyceride and cholesterol levels markedly decreased in the FO12.5 and FO25 groups, but not in the LSO group. Although plasma insulin levels did not differ among groups, the blood glucose areas under the curve in the oral glucose tolerance test were significantly lower in the FO12.5 and FO25 groups. Real-time polymerase chain reaction analysis showed fatty acid synthase mRNA levels significantly decreased in the FO25 group, and stearoyl-CoA desaturase 1 mRNA levels markedly decreased in the FO12.5 and FO25 groups. These results demonstrate that body weight gains were suppressed by dietary fat energy restriction even in KK mice with HF diet-induced obesity. We also suggested that the combination of fat energy restriction and fish oil feeding decreased fat droplets and ameliorated hepatic hypertrophy and insulin resistance with suppression of de novo lipogenesis in these mice. Copyright © 2013 Elsevier Inc. All rights reserved.

Consequences of Food Restriction for Immune Defense, Parasite Infection, and Fitness in Monarch Butterflies.

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McKay, Alexa Fritzsche; Ezenwa, Vanessa O; Altizer, Sonia

2016-01-01

Organisms have a finite pool of resources to allocate toward multiple competing needs, such as development, reproduction, and enemy defense. Abundant resources can support investment in multiple traits simultaneously, but limited resources might promote trade-offs between fitness-related traits and immune defenses. We asked how food restriction at both larval and adult life stages of the monarch butterfly (Danaus plexippus) affected measures of immunity, fitness, and immune-fitness interactions. We experimentally infected a subset of monarchs with a specialist protozoan parasite to determine whether parasitism further affected these relationships and whether food restriction influenced the outcome of infection. Larval food restriction reduced monarch fitness measures both within the same life stage (e.g., pupal mass) as well as later in life (e.g., adult lifespan); adult food restriction further reduced adult lifespan. Larval food restriction lowered both hemocyte concentration and phenoloxidase activity at the larval stage, and the effects of larval food restriction on phenoloxidase activity persisted when immunity was sampled at the adult stage. Adult food restriction reduced only adult phenoloxidase activity but not hemocyte concentration. Parasite spore load decreased with one measure of larval immunity, but food restriction did not increase the probability of parasite infection. Across monarchs, we found a negative relationship between larval hemocyte concentration and pupal mass, and a trade-off between adult hemocyte concentration and adult life span was evident in parasitized female monarchs. Adult life span increased with phenoloxidase activity in some subsets of monarchs. Our results emphasize that food restriction can alter fitness and immunity across multiple life stages. Understanding the consequences of resource limitation for immune defense is therefore important for predicting how increasing constraints on wildlife resources will affect fitness and

Newer antidiabetic drugs and calorie restriction mimicry

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Sanjay Kalra

2016-01-01

Full Text Available De-acceleration of aging and delayed development of age-related morbidity accompanies the restriction of calories (without malnutrition in laboratory mice, nematodes, yeast, fish, and dogs. Recent results from long-term longitudinal studies conducted on primates have suggested longevity benefits of a 30% restriction of calories in rhesus monkeys as well. Among calorie restricted rhesus monkeys one of the mechanisms for the improvement in lifespan was the reduction in the development of glucose intolerance and cardiovascular disease. Although there are no comparable human studies, it is likely that metabolic and longevity benefits will accompany a reduction in calories in humans as well. However, considering the difficulties in getting healthy adults to limit food intake science has focused on understanding the biochemical processes that accompany calorie restriction (CR to formulate drugs that would mimic the effects of CR without the need to actually restrict calories. Drugs in this emerging therapeutic field are called CR mimetics. Some of the currently used anti-diabetic agents may have some CR mimetic like effects. This review focuses on the CR mimetic properties of the currently available anti-diabetic agents.

Pain and symptoms of depression in older adults living in community and in nursing homes: the role of activity restriction as a potential mediator and moderator.

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López-Lopez, Almudena; González, José L; Alonso-Fernández, Miriam; Cuidad, Noelia; Matías, Borja

2014-10-01

Chronic pain is likely to lead to depressive symptoms, but the nature of this relationship is not completely clear. The aim of the present study is to analyze the role of activity restriction in the pain-depression relationship in older people, and to test the hypothesis that this role is more relevant in community-dwelling older people than in nursing home residents. Depressive symptoms, pain intensity, and activity restriction were measured in a sample of 208 older adults with osteoarthritis, 102 living in nursing homes (NH), and 106 in the community. Analyses were carried out using moderation and moderated mediation analyses approach, treating activity restriction as a confounder. RESULTS showed a significant confounding effect of activity restriction, interaction effect between pain intensity and activity restriction on depression, and modifying effect of pain intensity on depression by adding activity restriction into the model. These results suggest a potential mediating and moderating effects of activity restriction. Moreover, analyses suggest that, surprisingly, the strength of the mediation could be higher in nursing homes. Overall, it may be that what is really important to emotional well-being is not so much pain itself, but rather the way in which the pain alters older people's lives. The greater strength of the mediation in NH might be understood within the scope of self-determination theory. Generally speaking, the NH context has been considered as a coercive setting, promoting non-autonomous orientation. In this context, when events are objectively coercive, people may lack perceived autonomy and hence be at greater risk of depression.

If you can't eat what you like, like what you can: How coeliac disease patients and their families construct dietary restrictions as a matter of choice

NARCIS (Netherlands)

van der Veen, M.; te Molder, Hedwig Frederica Maria; Gremmen, B.; van Woerkum, C.

2013-01-01

Although it is recognised that a gluten-free diet has many social implications for coeliac disease patients, not much is known about how such patients actually manage these implications in their everyday interactions. This article examines how dietary restrictions are treated by patients and their

Docosahexaenoic Acid and Cognition throughout the Lifespan

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Michael J. Weiser

2016-02-01

Full Text Available Docosahexaenoic acid (DHA is the predominant omega-3 (n-3 polyunsaturated fatty acid (PUFA found in the brain and can affect neurological function by modulating signal transduction pathways, neurotransmission, neurogenesis, myelination, membrane receptor function, synaptic plasticity, neuroinflammation, membrane integrity and membrane organization. DHA is rapidly accumulated in the brain during gestation and early infancy, and the availability of DHA via transfer from maternal stores impacts the degree of DHA incorporation into neural tissues. The consumption of DHA leads to many positive physiological and behavioral effects, including those on cognition. Advanced cognitive function is uniquely human, and the optimal development and aging of cognitive abilities has profound impacts on quality of life, productivity, and advancement of society in general. However, the modern diet typically lacks appreciable amounts of DHA. Therefore, in modern populations, maintaining optimal levels of DHA in the brain throughout the lifespan likely requires obtaining preformed DHA via dietary or supplemental sources. In this review, we examine the role of DHA in optimal cognition during development, adulthood, and aging with a focus on human evidence and putative mechanisms of action.

Carbohydrate restriction and dietary cholesterol modulate the expression of HMG-CoA reductase and the LDL receptor in mononuclear cells from adult men

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Volek Jeff S

2007-11-01

Full Text Available Abstract The liver is responsible for controlling cholesterol homeostasis in the body. HMG-CoA reductase and the LDL receptor (LDL-r are involved in this regulation and are also ubiquitously expressed in all major tissues. We have previously shown in guinea pigs that there is a correlation in gene expression of HMG-CoA reductase and the LDL-r between liver and mononuclear cells. The present study evaluated human mononuclear cells as a surrogate for hepatic expression of these genes. The purpose was to evaluate the effect of dietary carbohydrate restriction with low and high cholesterol content on HMG-CoA reductase and LDL-r mRNA expression in mononuclear cells. All subjects were counseled to consume a carbohydrate restricted diet with 10–15% energy from carbohydrate, 30–35% energy from protein and 55–60% energy from fat. Subjects were randomly assigned to either EGG (640 mg/d additional dietary cholesterol or SUB groups [equivalent amount of egg substitute (0 dietary cholesterol contributions per day] for 12 weeks. At the end of the intervention, there were no changes in plasma total or LDL cholesterol (LDL-C compared to baseline (P > 0.10 or differences in plasma total or LDL-C between groups. The mRNA abundance for HMG-CoA reductase and LDL-r were measured in mononuclear cells using real time PCR. The EGG group showed a significant decrease in HMG-CoA reductase mRNA (1.98 ± 1.26 to 1.32 ± 0.92 arbitrary units P

Injuries can prolong lifespan in Drosophila melanogaster males

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Henten, Anne Marie Vestergaard; Loeschcke, Volker; Pedersen, Jørgen Granfeldt

2016-01-01

Previous studies have shown that a range of different stresses can increase mean lifespan. Here we investigated the effect of injuries and bacterial inoculation on mean lifespan in lines selected for increased longevity and their controls. The three lines from each selection regime were subjected...

Food cravings discriminate between anorexia and bulimia nervosa. Implications for "success" versus "failure" in dietary restriction.

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Moreno, Silvia; Warren, Cortney S; Rodríguez, Sonia; Fernández, M Carmen; Cepeda-Benito, Antonio

2009-06-01

Food cravings are subjective, motivational states thought to induce binge eating among eating disorder patients. This study compared food cravings across eating disorders. Women (N=135) diagnosed with anorexia nervosa, restrictive (ANR) or binge-purging (ANBP) types, or bulimia nervosa, non-purging (BNNP) or purging (BNP) types completed measures of food cravings. Discriminant analysis yielded two statistically significant functions. The first function differentiated between all the four group pairs except ANBP and BNNP, with levels of various food-craving dimensions successively increasing for ANR, ANBP, BNNP, and BNP participants. The second function differentiated between ANBP and BNNP participants. Overall, the functions improved classification accuracy above chance level (44% fewer errors). The findings suggest that cravings are more strongly associated with loss of control over eating than with dietary restraint tendencies.

Autism through the Lifespan

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... Information Publications Awards Partners Contact Us ¿Qué es Autismo? Donate Home What is Autism? What is Autism? ... Information Publications Awards Partners Contact Us ¿Qué es Autismo? Autism through the Lifespan Home / Living with Autism / ...

Inhibition of microtubules and dynein rescues human immunodeficiency virus type 1 from owl monkey TRIMCyp-mediated restriction in a cellular context-specific fashion.

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Pawlica, Paulina; Dufour, Caroline; Berthoux, Lionel

2015-04-01

IFN-induced restriction factors can significantly affect the replicative capacity of retroviruses in mammals. TRIM5α (tripartite motif protein 5, isoform α) is a restriction factor that acts at early stages of the virus life cycle by intercepting and destabilizing incoming retroviral cores. Sensitivity to TRIM5α maps to the N-terminal domain of the retroviral capsid proteins. In several New World and Old World monkey species, independent events of retrotransposon-mediated insertion of the cyclophilin A (CypA)-coding sequence in the trim5 gene have given rise to TRIMCyp (also called TRIM5-CypA), a hybrid protein that is active against some lentiviruses in a species-specific fashion. In particular, TRIMCyp from the owl monkey (omkTRIMCyp) very efficiently inhibits human immunodeficiency virus type 1 (HIV-1). Previously, we showed that disrupting the integrity of microtubules (MTs) and of cytoplasmic dynein complexes partially rescued replication of retroviruses, including HIV-1, from restriction mediated by TRIM5α. Here, we showed that efficient restriction of HIV-1 by omkTRIMCyp was similarly dependent on the MT network and on dynein complexes, but in a context-dependent fashion. When omkTRIMCyp was expressed in human HeLa cells, restriction was partially counteracted by pharmacological agents targeting MTs or by small interfering RNA-mediated inhibition of dynein. The same drugs (nocodazole and paclitaxel) also rescued HIV-1 from restriction in cat CRFK cells, although to a lesser extent. Strikingly, neither nocodazole, paclitaxel nor depletion of the dynein heavy chain had a significant effect on the restriction of HIV-1 in an owl monkey cell line. These results suggested the existence of cell-specific functional interactions between MTs/dynein and TRIMCyp. © 2015 The Authors.

Measurement of lifespan in Drosophila melanogaster.

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Linford, Nancy J; Bilgir, Ceyda; Ro, Jennifer; Pletcher, Scott D

2013-01-07

Aging is a phenomenon that results in steady physiological deterioration in nearly all organisms in which it has been examined, leading to reduced physical performance and increased risk of disease. Individual aging is manifest at the population level as an increase in age-dependent mortality, which is often measured in the laboratory by observing lifespan in large cohorts of age-matched individuals. Experiments that seek to quantify the extent to which genetic or environmental manipulations impact lifespan in simple model organisms have been remarkably successful for understanding the aspects of aging that are conserved across taxa and for inspiring new strategies for extending lifespan and preventing age-associated disease in mammals. The vinegar fly, Drosophila melanogaster, is an attractive model organism for studying the mechanisms of aging due to its relatively short lifespan, convenient husbandry, and facile genetics. However, demographic measures of aging, including age-specific survival and mortality, are extraordinarily susceptible to even minor variations in experimental design and environment, and the maintenance of strict laboratory practices for the duration of aging experiments is required. These considerations, together with the need to practice careful control of genetic background, are essential for generating robust measurements. Indeed, there are many notable controversies surrounding inference from longevity experiments in yeast, worms, flies and mice that have been traced to environmental or genetic artifacts(1-4). In this protocol, we describe a set of procedures that have been optimized over many years of measuring longevity in Drosophila using laboratory vials. We also describe the use of the dLife software, which was developed by our laboratory and is available for download (http://sitemaker.umich.edu/pletcherlab/software). dLife accelerates throughput and promotes good practices by incorporating optimal experimental design, simplifying

Dietary Calcium and Dairy Modulation of Oxidative Stress and Mortality in aP2-Agouti and Wild-type Mice

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Antje Bruckbauer

2009-08-01

Full Text Available Oxidative and inflammatory stress have been implicated as major contributors to the aging process. Dietary Ca reduced both factors in short-term interventions, while milk exerted a greater effect than supplemental Ca. In this work, we examined the effects of life-long supplemental and dairy calcium on lifespan and life-span related biomarkers in aP2-agouti transgenic (model of diet-induced obesity and wild-type mice fed obesigenic diets until their death. These data demonstrate that dairy Ca exerts sustained effects resulting in attenuated adiposity, protection against age-related muscle loss and reduction of oxidative and inflammatory stress in both mouse strains. Although these effects did not alter maximum lifespan, they did suppress early mortality in wild-type mice, but not in aP2-agouti transgenic mice.

Uncoupling of oxidative stress resistance and lifespan in long-lived isp-1 mitochondrial mutants in Caenorhabditis elegans.

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Dues, Dylan J; Schaar, Claire E; Johnson, Benjamin K; Bowman, Megan J; Winn, Mary E; Senchuk, Megan M; Van Raamsdonk, Jeremy M

2017-07-01

Mutations affecting components of the mitochondrial electron transport chain have been shown to increase lifespan in multiple species including the worm Caenorhabditis elegans. While it was originally proposed that decreased generation of reactive oxygen species (ROS) resulting from lower rates of electron transport could account for the observed increase in lifespan, recent evidence indicates that ROS levels are increased in at least some of these long-lived mitochondrial mutants. Here, we show that the long-lived mitochondrial mutant isp-1 worms have increased resistance to oxidative stress. Our results suggest that elevated ROS levels in isp-1 worms cause the activation of multiple stress-response pathways including the mitochondrial unfolded protein response, the SKN-1-mediated stress response, and the hypoxia response. In addition, these worms have increased expression of specific antioxidant enzymes, including a marked upregulation of the inducible superoxide dismutase genes sod-3 and sod-5. Examining the contribution of sod-3 and sod-5 to the oxidative stress resistance in isp-1 worms revealed that loss of either of these genes increased resistance to oxidative stress, but not other forms of stress. Deletion of sod-3 or sod-5 decreased the lifespan of isp-1 worms and further exacerbated their slow physiologic rates. Thus, while deletion of sod-3 and sod-5 genes has little impact on stress resistance, physiologic rates or lifespan in wild-type worms, these genes are required for the longevity of isp-1 worms. Overall, this work shows that the increased resistance to oxidative stress in isp-1 worms does not account for their longevity, and that resistance to oxidative stress can be experimentally dissociated from lifespan. Copyright © 2017 Elsevier Inc. All rights reserved.

Circadian clocks govern calorie restriction-mediated life span extension through BMAL1- and IGF-1-dependent mechanisms.

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Patel, Sonal A; Chaudhari, Amol; Gupta, Richa; Velingkaar, Nikkhil; Kondratov, Roman V

2016-04-01

Calorie restriction (CR) increases longevity in many species by unknown mechanisms. The circadian clock was proposed as a potential mediator of CR. Deficiency of the core component of the circadian clock-transcriptional factor BMAL1 (brain and muscle ARNT [aryl hydrocarbon receptor nuclear translocator]-like protein 1)-results in accelerated aging. Here we investigated the role of BMAL1 in mechanisms of CR. The 30% CR diet increased the life span of wild-type (WT) mice by 20% compared to mice on anad libitum(AL) diet but failed to increase life span ofBmal1(-/-)mice. BMAL1 deficiency impaired CR-mediated changes in the plasma levels of IGF-1 and insulin. We detected a statistically significantly reduction of IGF-1 in CRvs.AL by 50 to 70% in WT mice at several daily time points tested, while inBmal1(-/-)the reduction was not significant. Insulin levels in WT were reduced by 5 to 9%, whileBmal1(-/-)induced it by 10 to 35% at all time points tested. CR up-regulated the daily average expression ofBmal1(by 150%) and its downstream target genesPeriods(by 470% forPer1and by 130% forPer2). We propose that BMAL1 is an important mediator of CR, and activation of BMAL1 might link CR mechanisms with biologic clocks.-Patel, S. A., Chaudhari, A., Gupta, R., Velingkaar, N., Kondratov, R. V. Circadian clocks govern calorie restriction-mediated life span extension through BMAL1- and IGF-1-dependent mechanisms. © FASEB.

Human Ageing Genomic Resources: Integrated databases and tools for the biology and genetics of ageing

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Tacutu, Robi; Craig, Thomas; Budovsky, Arie; Wuttke, Daniel; Lehmann, Gilad; Taranukha, Dmitri; Costa, Joana; Fraifeld, Vadim E.; de Magalhães, João Pedro

2013-01-01

The Human Ageing Genomic Resources (HAGR, http://genomics.senescence.info) is a freely available online collection of research databases and tools for the biology and genetics of ageing. HAGR features now several databases with high-quality manually curated data: (i) GenAge, a database of genes associated with ageing in humans and model organisms; (ii) AnAge, an extensive collection of longevity records and complementary traits for >4000 vertebrate species; and (iii) GenDR, a newly incorporated database, containing both gene mutations that interfere with dietary restriction-mediated lifespan extension and consistent gene expression changes induced by dietary restriction. Since its creation about 10 years ago, major efforts have been undertaken to maintain the quality of data in HAGR, while further continuing to develop, improve and extend it. This article briefly describes the content of HAGR and details the major updates since its previous publications, in terms of both structure and content. The completely redesigned interface, more intuitive and more integrative of HAGR resources, is also presented. Altogether, we hope that through its improvements, the current version of HAGR will continue to provide users with the most comprehensive and accessible resources available today in the field of biogerontology. PMID:23193293

Sedentary behaviour and diet across the lifespan: an updated systematic review.

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Hobbs, Matthew; Pearson, Natalie; Foster, Perry J; Biddle, Stuart J H

2015-09-01

Sedentary behaviour and its association with dietary intake in young people and adults are important topics and were systematically reviewed in 2011. There is a need to update this evidence given the changing nature of sedentary behaviour and continued interest in this field. This review aims to assist researchers in better interpreting the diversity of findings concerning sedentary behaviour and weight status. To provide an update of the associations between sedentary behaviour and dietary intake across the lifespan. Electronic databases searched were MEDLINE, PsychInfo, Cochrane Library, Web of Science and Science Direct for publications between January 2010 and October 2013, thus updating a previous review. Included were observational studies assessing an association between at least one sedentary behaviour and at least one aspect of dietary intake in preschool children (18 years). 27 papers met inclusion criteria (preschool k=3, school-aged children k=9, adolescents k=15, adults k=3). For all three groups of young people, trends were evident for higher levels of sedentary behaviour, especially TV viewing, to be associated with a less healthful diet, such as less fruit and vegetable and greater consumption of energy-dense snacks and sugar sweetened beverages. Data for the three studies with adults were less conclusive. Sedentary behaviour continues to be associated with unhealthy diet in young people in mostly cross-sectional studies. More studies utilising a prospective design are needed to corroborate findings and more studies are needed with adults. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Food-specific response inhibition, dietary restraint and snack intake in lean and overweight/obese adults: a moderated-mediation model.

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Price, M; Lee, M; Higgs, S

2016-05-01

The relationship between response inhibition and obesity is currently unclear. This may be because of inconsistencies in methodology, design limitations and the use of narrow samples. In addition, dietary restraint has not been considered, yet restraint has been reported to moderate performance on behavioural tasks of response inhibition. The aim of this study was to investigate performance on both a food-based and a neutral stimuli go/no-go task, which addresses current design limitations, in lean and overweight/obese adults. The moderating role of dietary restraint in the relationship between body composition, response inhibition and snack intake was also measured. Lean and overweight/obese, males and females (N=116) completed both a food-based and neutral category control go/no-go task, in a fully counterbalanced repeated-measures design. A bogus taste-test was then completed, followed by a self-report measure of dietary restraint. PROCESS moderated-mediation analysis showed that overweight/obese, compared with lean, participants made more errors on the food-based (but not the neutral) go/no-go task, but only when they were low in dietary restraint. Performance on the food-based go/no-go task predicted snack intake across the sample. Increased intake in the overweight, low restrainers was fully mediated by increased errors on the food-based (but not the neutral) go/no-go task. Distinguishing between high and low restrained eaters in the overweight/obese population is crucial in future obesity research incorporating food-based go/no-go tasks. Poor response inhibition to food cues predicts overeating across weight groups, suggesting weight loss interventions and obesity prevention programmes should target behavioural inhibition training in such individuals.

Impact of mothers' negative affectivity, parental locus of control and child-feeding practices on dietary patterns of 3-year-old children: the MoBa Cohort Study.

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Ystrom, Eivind; Barker, Mary; Vollrath, Margarete E

2012-01-01

The aims of the current study were to (1) identify dietary patterns in 3-year-old children; (2) investigate the extent to which negative affectivity, external parental locus of control and control-oriented child-feeding practices (pressure to eat and restriction) relate to these dietary patterns; and (3) to examine to what extent external parental locus of control and control-oriented child-feeding practices serve as mediators for these effects. This study was part of the Norwegian Mother and Child Cohort Study, comprising 14,122 mothers completing assessments at 6 months, 18 months and 3 years post-partum. Factor analysis of the children's diet identified two weakly correlated dietary patterns, labeled 'unhealthy' and 'wholesome'. Mothers high in negative affectivity perceived they had little control over their child's behaviour, which in turn was associated with both pressuring their child to eat and restricting the child's food intake and a less wholesome and a more unhealthy diet in the child. Pressuring the child to eat was independently associated with a less wholesome and a more unhealthy diet. Restricting the child's diet was associated with a more wholesome and a less unhealthy diet. These findings held after controlling for maternal smoking, education, age, body mass index, marital status, homemaker status and child gender. © 2010 Blackwell Publishing Ltd.

Age, gender, and cancer but not neurodegenerative and cardiovascular diseases strongly modulate systemic effect of the Apolipoprotein E4 allele on lifespan

DEFF Research Database (Denmark)

Kulminski, Alexander M; Arbeev, Konstantin G; Culminskaya, Irina

2014-01-01

cohorts and the Long Life Family Study (LLFS) to investigate gender-specific effects of the ApoE4 allele on human survival in a wide range of ages from midlife to extreme old ages, and the sensitivity of these effects to cardiovascular disease (CVD), cancer, and neurodegenerative disorders (ND.......6 × 10(-6)) in the FHS cohorts. Major human diseases including CVD, ND, and cancer, whose risks can be sensitive to the e4 allele, do not mediate the association of this allele with lifespan in large FHS samples. Non-skin cancer non-additively increases mortality of the FHS women with moderate lifespans...... by 150% (p = 5.3 × 10(-8)) compared to the non-carriers. This risk explains the 4.2 year shorter life expectancy of the e4 carriers compared to the non-carriers in this sample. The analyses suggest the existence of age- and gender-sensitive systemic mechanisms linking the e4 allele to lifespan which can...

Lack of Ach1 CoA-Transferase Triggers Apoptosis and Decreases Chronological Lifespan in Yeast

International Nuclear Information System (INIS)

Orlandi, Ivan; Casatta, Nadia; Vai, Marina

2012-01-01

ACH1 encodes a mitochondrial enzyme of Saccharomyces cerevisiae endowed with CoA-transferase activity. It catalyzes the CoASH transfer from succinyl-CoA to acetate generating acetyl-CoA. It is known that ACH1 inactivation results in growth defects on media containing acetate as a sole carbon and energy source which are particularly severe at low pH. Here, we show that chronological aging ach1Δ cells which accumulate a high amount of extracellular acetic acid display a reduced chronological lifespan. The faster drop of cell survival is completely abrogated by alleviating the acid stress either by a calorie restricted regimen that prevents acetic acid production or by transferring chronologically aging mutant cells to water. Moreover, the short-lived phenotype of ach1Δ cells is accompanied by reactive oxygen species accumulation, severe mitochondrial damage, and an early insurgence of apoptosis. A similar pattern of endogenous severe oxidative stress is observed when ach1Δ cells are cultured using acetic acid as a carbon source under acidic conditions. On the whole, our data provide further evidence of the role of acetic acid as cell-extrinsic mediator of cell death during chronological aging and highlight a primary role of Ach1 enzymatic activity in acetic acid detoxification which is important for mitochondrial functionality.

Biological functionalization of drug delivery carriers to bypass size restrictions of receptor-mediated endocytosis independently from receptor targeting.

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Ansar, Maria; Serrano, Daniel; Papademetriou, Iason; Bhowmick, Tridib Kumar; Muro, Silvia

2013-12-23

Targeting of drug carriers to cell-surface receptors involved in endocytosis is commonly used for intracellular drug delivery. However, most endocytic receptors mediate uptake via clathrin or caveolar pathways associated with ≤200-nm vesicles, restricting carrier design. We recently showed that endocytosis mediated by intercellular adhesion molecule 1 (ICAM-1), which differs from clathrin- and caveolae-mediated pathways, allows uptake of nano- and microcarriers in cell culture and in vivo due to recruitment of cellular sphingomyelinases to the plasmalemma. This leads to ceramide generation at carrier binding sites and formation of actin stress-fibers, enabling engulfment and uptake of a wide size-range of carriers. Here we adapted this paradigm to enhance uptake of drug carriers targeted to receptors associated with size-restricted pathways. We coated sphingomyelinase onto model (polystyrene) submicro- and microcarriers targeted to clathrin-associated mannose-6-phosphate receptor. In endothelial cells, this provided ceramide enrichment at the cell surface and actin stress-fiber formation, modifying the uptake pathway and enhancing carrier endocytosis without affecting targeting, endosomal transport, cell-associated degradation, or cell viability. This improvement depended on the carrier size and enzyme dose, and similar results were observed for other receptors (transferrin receptor) and cell types (epithelial cells). This phenomenon also enhanced tissue accumulation of carriers after intravenous injection in mice. Hence, it is possible to maintain targeting toward a selected receptor while bypassing natural size restrictions of its associated endocytic route by functionalization of drug carriers with biological elements mimicking the ICAM-1 pathway. This strategy holds considerable promise to enhance flexibility of design of targeted drug delivery systems.

Green Tea Polyphenols, Mimicking the Effects of Dietary Restriction, Ameliorate High-Fat Diet-Induced Kidney Injury via Regulating Autophagy Flux

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Xiao Xie

2017-05-01

Full Text Available Epidemiological and experimental studies reveal that Western dietary patterns contribute to chronic kidney disease, whereas dietary restriction (DR or dietary polyphenols such as green tea polyphenols (GTPs can ameliorate the progression of kidney injury. This study aimed to investigate the renal protective effects of GTPs and explore the underlying mechanisms. Sixty Wistar rats were randomly divided into 6 groups: standard diet (STD, DR, high-fat diet (HFD, and three diets plus 200 mg/kg(bw/day GTPs, respectively. After 18 weeks, HFD group exhibited renal injuries by increased serum cystatin C levels and urinary N-acetyl-β-d-glucosaminidase activity, which can be ameliorated by GTPs. Meanwhile, autophagy impairment as denoted by autophagy-lysosome related proteins, including LC3-II, Beclin-1, p62, cathepsin B, cathepsin D and LAMP-1, was observed in HFD group, whereas DR or GTPs promoted renal autophagy activities and GTPs ameliorated HFD-induced autophagy impairment. In vitro, autophagy flux suppression was detected in palmitic acid (PA-treated human proximal tubular epithelial cells (HK-2, which was ameliorated by epigallocatechin-3-gallate (EGCG. Furthermore, GTPs (or EGCG elevated phosphorylation of AMP-activated protein kinase in the kidneys of HFD-treated rats and in PA-treated HK-2 cells. These findings revealed that GTPs mimic the effects of DR to induce autophagy and exert a renal protective effect by alleviating HFD-induced autophagy suppression.

Dietary Sodium Modulation of Aldosterone Activation and Renal Function During the Progression of Experimental Heart Failure Miller: Dietary Sodium and Early Heart Failure

Science.gov (United States)

Miller, Wayne L.; Borgeson, Daniel D.; Grantham, J. Aaron; Luchner, Andreas; Redfield, Margaret M.; Burnett, John C.

2015-01-01

Aims Aldosterone activation is central to the sodium-fluid retention that marks the progression of heart failure (HF). The actions of dietary sodium restriction, a mainstay in HF management, on cardiorenal and neuroendocrine adaptations during the progression of HF are poorly understood. The study aim was to assess the role of dietary sodium during the progression of experimental HF. Methods and Results Experimental HF was produced in a canine model by rapid right ventricular pacing which evolves from early mild HF to overt, severe HF. Dogs were fed one of three diets: 1) high sodium [250 mEq (5.8 grams) per day, n=6]; 2) standard sodium [58 mEq (1.3 grams) per day, n=6]; and 3) sodium restriction [11 mEq (0.25 grams) per day, n=6]. During the 38 day study hemodynamics, renal function, renin activity (PRA), and aldosterone were measured. Changes in hemodynamics at 38 days were similar in all three groups, as were changes in renal function. Aldosterone activation was demonstrated in all three groups, however, dietary sodium restriction, in contrast to high sodium, resulted in early (10 days) activation of PRA and aldosterone. High sodium demonstrated significant suppression of aldosterone activation over the course of HF progression. Conclusions Excessive dietary sodium restriction particularly in early stage HF results in early aldosterone activation, while normal and excess sodium intake are associated with delayed or suppressed activation. These findings warrant evaluation in humans to determine if dietary sodium manipulation, particularly during early stage HF, may have a significant impact on neuroendocrine disease progression. PMID:25823360

Availability of Amino Acids Extends Chronological Lifespan by Suppressing Hyper-Acidification of the Environment in Saccharomyces cerevisiae.

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Yo Maruyama

Full Text Available The chronological lifespan of Saccharomyces cerevisiae represents the duration of cell survival in the postdiauxic and stationary phases. Using a prototrophic strain derived from the standard auxotrophic laboratory strain BY4742, we showed that supplementation of non-essential amino acids to a synthetic defined (SD medium increases maximal cell growth and extends the chronological lifespan. The positive effects of amino acids can be reproduced by modulating the medium pH, indicating that amino acids contribute to chronological longevity in a cell-extrinsic manner by alleviating medium acidification. In addition, we showed that the amino acid-mediated effects on extension of chronological longevity are independent of those achieved through a reduction in the TORC1 pathway, which is mediated in a cell-intrinsic manner. Since previous studies showed that extracellular acidification causes mitochondrial dysfunction and leads to cell death, our results provide a path to premature chronological aging caused by differences in available nitrogen sources. Moreover, acidification of culture medium is generally associated with culture duration and cell density; thus, further studies are required on cell physiology of auxotrophic yeast strains during the stationary phase because an insufficient supply of essential amino acids may cause alterations in environmental conditions.

Measurement of Dietary Restraint: Validity Tests of Four Questionnaires

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Williamson, Donald A.; Martin, Corby K.; York-Crowe, Emily; Anton, Stephen D.; Redman, Leanne M.; Han, Hongmei; Ravussin, Eric

2007-01-01

This study tested the validity of four measures of dietary restraint: Dutch Eating Behavior Questionnaire, Eating Inventory (EI), Revised Restraint Scale (RS), and the Current Dieting Questionnaire. Dietary restraint has been implicated as a determinant of overeating and binge eating. Conflicting findings have been attributed to different methods for measuring dietary restraint. The validity of four self-report measures of dietary restraint and dieting behavior was tested using: 1) factor analysis, 2) changes in dietary restraint in a randomized controlled trial of different methods to achieve calorie restriction, and 3) correlation of changes in dietary restraint with an objective measure of energy balance, calculated from the changes in fat mass and fat-free mass over a six-month dietary intervention. Scores from all four questionnaires, measured at baseline, formed a dietary restraint factor, but the RS also loaded on a binge eating factor. Based on change scores, the EI Restraint scale was the only measure that correlated significantly with energy balance expressed as a percentage of energy require d for weight maintenance. These findings suggest that that, of the four questionnaires tested, the EI Restraint scale was the most valid measure of the intent to diet and actual caloric restriction. PMID:17101191

Behavioural changes are a major contributing factor in the reduction of sarcopenia in caloric-restricted ageing mice

NARCIS (Netherlands)

Norren, van K.; Rusli, F.; Dijk, van M.; Lute, C.; Nagel, J.C.; Dijk, F.J.; Dwarkasing, J.T.; Boekschoten, M.V.; Luiking, Y.; Witkamp, R.F.; Müller, M.R.; Steegenga, W.T.

2015-01-01

Background - In rodent models, caloric restriction (CR) with maintenance of adequate micronutrient supply has been reported to increase lifespan and to reduce age-induced muscle loss (sarcopenia) during ageing. In the present study, we further investigated effects of CR on the onset and severity of

Discriminating between energetic content and dietary composition as an explanation for dietary restriction effects.

NARCIS (Netherlands)

Ellers, J.; Ruhe, B.; Visser, B.

2011-01-01

A reduction in dietary calories has been shown to prolong life span in a wide variety of taxa, but there has been much debate about confounding factors such as nutritional composition of the diet, or reallocation of nutrients from reduced reproduction. To disentangle the contribution of these

Effect of moderate dietary restriction on visceral organ weight, hepatic oxygen consumption, and metabolic proteins associated with energy balance in mature pregnant beef cows.

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Wood, K M; Awda, B J; Fitzsimmons, C; Miller, S P; McBride, B W; Swanson, K C

2013-09-01

Twenty-two nonlactating multiparous pregnant beef cows (639 ± 68 kg) were used to investigate the effect of dietary restriction on the abundance of selected proteins regulating cellular energy metabolism. Cows were fed at either 85% (n = 11; LOW) or 140% (n = 11; HIGH) of total NE requirements. The diet consisted of a haylage-based total mixed ration containing 20% wheat straw. Cows were slaughtered by block (predicted date of parturition), beginning 83 d after the initiation of dietary treatments and every week thereafter for 6 wk, such that each block was slaughtered at approximately 250 d of gestation. Tissue samples from liver, kidney, sternomandibularis muscle, ruminal papilli (ventral sac), pancreas, and small intestinal muscosa were collected at slaughter and snap frozen in liquid N2. Western blots were conducted to quantify abundance of proliferating cell nuclear antigen (PCNA), ATP synthase, ubiquitin, and Na/K+ ATPase for all tissues; PPARγ, PPARγ coactivator 1 α (PGC-1α), and 5´-adenosine monophosphate-activated protein kinase (AMPK) and the activated form phosphorylated-AMPK (pAMPK) for liver, muscle, and rumen; phosphoenolpyruvate carboxykinase (PEPCK) for liver and kidney; and uncoupling protein 2 (UCP2) for liver. Statistical analysis was conducted using Proc Mixed in SAS and included the fixed effects of dietary treatment, cow age, block, and the random effect of pen. Dietary treatments resulted in cows fed HIGH having greater (P ≤ 0.04) ADG and final BW than cows fed LOW. Abundance of ubiquitin in muscle was greater (P = 0.009) in cows fed LOW, and PCG-1 α in liver was greater (P = 0.03) in cows fed HIGH. Hepatic O2 consumption was greater in HIGH (P ≤ 0.04). Feed intake can influence the abundance of important metabolic proteins and suggest that protein degradation may increase in muscle from moderately nutrient restricted cows and that energy metabolism in liver increases in cows fed above NE requirements.

Adaptação transcultural para o Brasil do Dietary Sodium Restriction Questionnaire (Questionário Restritivo da Dieta de Sódio (DSRQ Adaptación transcultural para Brasil del dietary sodium restriction questionnaire (Cuestionario Restrictivo de la Dieta de Sodio (DSRQ Cross-cultural adaptation into Brazilian portuguese of the Dietary Sodium Restriction Questionnaire (DSRQ

Directory of Open Access Journals (Sweden)

Karina Sanches Machado d'Almeida

2012-01-01

Full Text Available FUNDAMENTO: A restrição de sódio é uma medida não farmacológica frequentemente orientada aos pacientes com Insuficiência Cardíaca (IC. No entanto, a adesão é de baixa prevalência, ficando entre as causas mais frequentes de descompensação da IC. O Dietary Sodium Restriction Questionnaire (DSRQ tem como objetivo identificar fatores que afetam a adesão à restrição dietética de sódio para pacientes com IC. No Brasil, não existem instrumentos que avaliem tais fatores. OBJETIVO: Realizar a adaptação transcultural do DSRQ. MÉTODOS: Estudo metodológico que envolveu as seguintes etapas: tradução, síntese, retrotradução, revisão por um comitê de especialistas, pré-teste da versão final e análise de concordância interobservador. No pré-teste foram avaliados os itens e sua compreensão, além da consistência interna pelo coeficiente alfa de Cronbach. O instrumento foi aplicado por dois pesquisadores simultânea e independentemente, sendo utilizado o teste Kappa para análise da concordância. RESULTADOS: Apenas uma questão sofreu alterações semânticas e/ou culturais maiores. No pré-teste, o alfa de Cronbach obtido para o total foi de 0,77, e para as escalas de Atitude, Norma subjetiva e Controle Comportamental obtiveram-se, respectivamente, 0,66, 0,50 e 0,85. Na etapa de concordância, o Kappa foi calculado para 12 das 16 questões, com valores que variaram de 0,62 a 1,00. Nos itens em que o cálculo não foi possível, a incidência de respostas iguais variou de 95% a 97,5%. CONCLUSÃO: A partir da adaptação transcultural do DSRQ foi possível propor uma versão do questionário para posterior avaliação das propriedades psicométricas.FUNDAMENTO: La restricción de sodio es una medida no farmacológica a menudo dirigida a los pacientes con Insuficiencia Cardíaca (IC. Sin embargo, la adhesión es de baja prevalencia, y queda entre las causas más comunes de descompensación de la IC. El Dietary Sodium

Impact of diet restriction in the management of diabetes: evidences from preclinical studies.

Science.gov (United States)

Krishan, Pawan; Bedi, Onkar; Rani, Monika

2018-03-01

The inappropriate dietary habits lead to the onset of age-related pathologies which include diabetes and cardiovascular ailments. Dietary restriction and nutritional therapy play an important role in the prevention of these chronic ailments. Preclinical research provides a basis for the therapeutic exploration of new dietary interventions for the clinical trials to potentiate the scientific management of diabetes and its related complications which further help in translating these nutritional improvements from bench to bedside. Within the same context, numerous therapeutically proved preclinical dietary interventions like high-fiber diet, caloric restriction, soy isoflavone-containing diets, etc., have shown the promising results for the management of diabetes and the associated complications. The focus of the present review is to highlight the various preclinical evidences of diet restriction for the management of diabetes and which will be helpful for enlightening the new ideas of nutritional therapy for future research exploration. In addition, some potential approaches are also discussed which are associated with various nutritional interventions to combat progressive diabetes and the associated disorders. Graphical abstract ᅟ.

Transcription factor genes essential for cell proliferation and replicative lifespan in budding yeast

Energy Technology Data Exchange (ETDEWEB)

Kamei, Yuka; Tai, Akiko; Dakeyama, Shota; Yamamoto, Kaori; Inoue, Yamato; Kishimoto, Yoshifumi; Ohara, Hiroya; Mukai, Yukio, E-mail: y_mukai@nagahama-i-bio.ac.jp

2015-07-31

Many of the lifespan-related genes have been identified in eukaryotes ranging from the yeast to human. However, there is limited information available on the longevity genes that are essential for cell proliferation. Here, we investigated whether the essential genes encoding DNA-binding transcription factors modulated the replicative lifespan of Saccharomyces cerevisiae. Heterozygous diploid knockout strains for FHL1, RAP1, REB1, and MCM1 genes showed significantly short lifespan. {sup 1}H-nuclear magnetic resonance analysis indicated a characteristic metabolic profile in the Δfhl1/FHL1 mutant. These results strongly suggest that FHL1 regulates the transcription of lifespan related metabolic genes. Thus, heterozygous knockout strains could be the potential materials for discovering further novel lifespan genes. - Highlights: • Involvement of yeast TF genes essential for cell growth in lifespan was evaluated. • The essential TF genes, FHL1, RAP1, REB1, and MCM1, regulate replicative lifespan. • Heterozygous deletion of FHL1 changes cellular metabolism related to lifespan.

Effect Of Feed Restriction On Growth Performance And Economy Of ...

African Journals Online (AJOL)

The dietary treatments consisted of providing feed ad libitum (ull fed) and two feed restriction treatments restrictingeedng 80 % of ad libitum ... A cost – benefit analysis was utilized for the economy of production. ... Feed efficiency was improved by restriction followed with re-alimentation. ... AJOL African Journals Online.

Positive Social Interactions in a Lifespan Perspective with a Focus on Opioidergic and Oxytocinergic Systems: Implications for Neuroprotection

Science.gov (United States)

Colonnello, Valentina; Petrocchi, Nicola; Farinelli, Marina; Ottaviani, Cristina

2017-01-01

In recent years, a growing interest has emerged in the beneficial effects of positive social interactions on health. The present work aims to review animal and human studies linking social interactions and health throughout the lifespan, with a focus on current knowledge of the possible mediating role of opioids and oxytocin. During the prenatal period, a positive social environment contributes to regulating maternal stress response and protecting the fetus from exposure to maternal active glucocorticoids. Throughout development, positive social contact with the caregiver acts as a “hidden regulator” and promotes infant neuroaffective development. Postnatal social neuroprotection interventions involving caregiver–infant physical contact seem to be crucial for rescuing preterm infants at risk for neurodevelopmental disorders. Attachment figures and friendships in adulthood continue to have a protective role for health and brain functioning, counteracting brain aging. In humans, implementation of meditative practices that promote compassionate motivation and prosocial behavior appears beneficial for health in adolescents and adults. Human and animal studies suggest the oxytocinergic and opioidergic systems are important mediators of the effects of social interactions. However, most of the studies focus on a specific phase of life (i.e., adulthood). Future studies should focus on the role of opioids and oxytocin in positive social interactions adopting a lifespan perspective. PMID:27538784

The Lifespan of Ornaments

DEFF Research Database (Denmark)

Munch, Anders V.; Riisberg, Vibeke

? In this paper we will look at contemporary use of ornament in different scales and contexts – from fashion textiles and interior objects to architecture. The lifespan of a building is different from that of a fashion dress or a plate, but with the digital era it seems like the concern of appropriateness...

Vitellogenin family gene expression does not increase Drosophila lifespan or fecundity [v1; ref status: indexed, http://f1000r.es/3ac

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Yingxue Ren

2014-06-01

Full Text Available One of the most striking patterns in comparative biology is the negative correlation between lifespan and fecundity observed in comparisons among species. This pattern is consistent with the idea that organisms need to allocate a fixed energy budget among competing demands of growth, development, reproduction and somatic maintenance. However, exceptions to this pattern have been observed in many social insects, including ants, bees, and termites.  In honey bees (Apis mellifera, Vitellogenin (Vg, a yolk protein precursor, has been implicated in mediating the long lifespan and high fecundity of queen bees. To determine if Vg-like proteins can regulate lifespan in insects generally, we examined the effects of expression of Apis Vg and Drosophila CG31150 (a Vg-like gene recently identified as cv-d on Drosophila melanogaster lifespan and fecundity using the RU486-inducible GeneSwitch system. For all genotypes tested, overexpression of Vg and CG31150 decreased Drosophila lifespan and did not affect total or age-specific fecundity. We also detected an apparent effect of the GeneSwitch system itself, wherein RU486 exposure (or the GAL4 expression it induces led to a significant increase in longevity and decrease in fecundity in our fly strains. This result is consistent with the pattern reported in a recent meta-analysis of Drosophila aging studies, where transgenic constructs of the UAS/GAL4 expression system that should have no effect (e.g. an uninduced GeneSwitch significantly extended lifespan in some genetic backgrounds. Our results suggest that Vg-family genes are not major regulators of Drosophila life history traits, and highlight the importance of using appropriate controls in aging studies.

Lactobacillus salivarius strain FDB89 induced longevity in Caenorhabditis elegans by dietary restriction.

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Zhao, Yang; Zhao, Liang; Zheng, Xiaonan; Fu, Tianjiao; Guo, Huiyuan; Ren, Fazheng

2013-04-01

In this study, we utilized the nematode Caenorhabditis elegans to assess potential life-expanding effect of Lactobacillus salivarius strain FDB89 (FDB89) isolated from feces of centenarians in Bama County (Guangxi, China). This study showed that feeding FDB89 extended the mean life span in C. elegans by up to 11.9% compared to that of control nematodes. The reduced reproductive capacities, pharyngeal pumping rate, growth, and increased superoxide dismutase (SOD) activity and XTT reduction capacity were also observed in FDB89 feeding worms. To probe the anti-aging mechanism further, we incorporated a food gradient feeding assay and assayed the life span of eat-2 mutant. The results demonstrated that the maximal life span of C. elegans fed on FDB89 was achieved at the concentration of 1.0 mg bacterial cells/plate, which was 10-fold greater than that of C. elegans fed on E. coli OP50 (0.1 mg bacterial cells/plate). However, feeding FDB89 could not further extend the life span of eat-2 mutant. These results indicated that FDB89 modulated the longevity of C. elegans in a dietary restriction-dependent manner and expanded the understanding of anti-aging effect of probiotics.

Lifespan extension by preserving proliferative homeostasis in Drosophila.

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Benoît Biteau

2010-10-01

Full Text Available Regenerative processes are critical to maintain tissue homeostasis in high-turnover tissues. At the same time, proliferation of stem and progenitor cells has to be carefully controlled to prevent hyper-proliferative diseases. Mechanisms that ensure this balance, thus promoting proliferative homeostasis, are expected to be critical for longevity in metazoans. The intestinal epithelium of Drosophila provides an accessible model in which to test this prediction. In aging flies, the intestinal epithelium degenerates due to over-proliferation of intestinal stem cells (ISCs and mis-differentiation of ISC daughter cells, resulting in intestinal dysplasia. Here we show that conditions that impair tissue renewal lead to lifespan shortening, whereas genetic manipulations that improve proliferative homeostasis extend lifespan. These include reduced Insulin/IGF or Jun-N-terminal Kinase (JNK signaling activities, as well as over-expression of stress-protective genes in somatic stem cell lineages. Interestingly, proliferative activity in aging intestinal epithelia correlates with longevity over a range of genotypes, with maximal lifespan when intestinal proliferation is reduced but not completely inhibited. Our results highlight the importance of the balance between regenerative processes and strategies to prevent hyperproliferative disorders and demonstrate that promoting proliferative homeostasis in aging metazoans is a viable strategy to extend lifespan.

When less may be more: calorie restriction and response to cancer therapy

OpenAIRE

O?Flanagan, Ciara H.; Smith, Laura A.; McDonell, Shannon B.; Hursting, Stephen D.

2017-01-01

Calorie restriction (CR) extends lifespan and has been shown to reduce age-related diseases including cancer, diabetes, and cardiovascular and neurodegenerative diseases in experimental models. Recent translational studies have tested the potential of CR or CR mimetics as adjuvant therapies to enhance the efficacy of chemotherapy, radiation therapy, and novel immunotherapies. Chronic CR is challenging to employ in cancer patients, and therefore intermittent fasting, CR mimetic drugs, or alter...

Dietary Quality and Adherence to Dietary Recommendations in Patients Undergoing Hemodialysis.

Science.gov (United States)

Luis, Desiree; Zlatkis, Karyn; Comenge, Beatriz; García, Zoraida; Navarro, Juan F; Lorenzo, Victor; Carrero, Juan Jesús

2016-05-01

The multiple dietary restrictions recommended to hemodialysis patients may be difficult to achieve and, at the same time, may result in nutritional deficiencies rendering a poor dietary quality. We here assess the dietary quality and adherence to renal-specific guideline recommendations among hemodialysis patients from a single center in Canary Islands, Spain. Cross-sectional study, including 91 patients undergoing maintenance hemodialysis. Clinical data and 3-day dietary records were collected. We compared patient's reported nutrients intake with guideline recommendations. We also evaluated their alignment with current American Heart Association dietary guidelines for cardiovascular prevention. Seventy-seven percent and 50% of patients consumed less than the recommended daily energy and protein, respectively. Although half of the patients met the recommendations for dietary fat intake, this was accounted by an excess of saturated fat in 92% of them. Only 22% consumed sufficient fiber. A very small proportion of patients (less than 50%) met the requirements for vitamins and other micronutrients. Insufficient dietary intake was observed in most patients for all vitamins except for cobalamin. Similarly, inadequate dietary intake was observed for many minerals, by both excess (phosphorus, calcium, sodium, and potassium) and defect (magnesium). Most patients met the recommendations for iron and zinc in their diets. A large proportion of hemodialysis patients at our center did not meet current renal-specific dietary recommendations. The quality of the diet was considered poor and proatherogenic according to American Heart Association guidelines. Copyright © 2016 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Dietary Restriction Affects Neuronal Response Property and GABA Synthesis in the Primary Visual Cortex.

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Yang, Jinfang; Wang, Qian; He, Fenfen; Ding, Yanxia; Sun, Qingyan; Hua, Tianmiao; Xi, Minmin

2016-01-01

Previous studies have reported inconsistent effects of dietary restriction (DR) on cortical inhibition. To clarify this issue, we examined the response properties of neurons in the primary visual cortex (V1) of DR and control groups of cats using in vivo extracellular single-unit recording techniques, and assessed the synthesis of inhibitory neurotransmitter GABA in the V1 of cats from both groups using immunohistochemical and Western blot techniques. Our results showed that the response of V1 neurons to visual stimuli was significantly modified by DR, as indicated by an enhanced selectivity for stimulus orientations and motion directions, decreased visually-evoked response, lowered spontaneous activity and increased signal-to-noise ratio in DR cats relative to control cats. Further, it was shown that, accompanied with these changes of neuronal responsiveness, GABA immunoreactivity and the expression of a key GABA-synthesizing enzyme GAD67 in the V1 were significantly increased by DR. These results demonstrate that DR may retard brain aging by increasing the intracortical inhibition effect and improve the function of visual cortical neurons in visual information processing. This DR-induced elevation of cortical inhibition may favor the brain in modulating energy expenditure based on food availability.

The effect of different levels of dietary restriction on glucose homeostasis and metabolic memory.

Science.gov (United States)

Matyi, Stephanie; Jackson, Jordan; Garrett, Karla; Deepa, Sathyaseelan S; Unnikrishnan, Archana

2018-02-17

Over the past 50 years, dietary restriction (DR) has been shown to extend the life span of a wide variety of organisms. A hallmark feature of DR is improved glucose homeostasis resulting in increased glucose tolerance and insulin sensitivity of animals ranging from rodents to humans. In this study, we demonstrate the early effects of varying levels of DR on glucose tolerance. Within 10 days of 40% DR, glucose tolerance was significantly improved and by 120 days; 10 and 20% DR also showed enhanced glucose tolerance. All three levels of DR showed reduced adiposity, increased expression of genes involved in fat turnover, and a reduction in the expression for markers of inflammation. Studies have shown that mice fed a DR diet retained metabolic memory in terms of improved glucose tolerance even after DR is discontinued. We show that 40% DR not only has an early effect on glucose tolerance but also maintained it after DR was discontinued for 2 months. Therefore, improvement in glucose tolerance is brought about by all three levels of DR but the metabolic memory is not dose responsive.

Middle age onset short-term intermittent fasting dietary restriction prevents brain function impairments in male Wistar rats.

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Singh, Rumani; Manchanda, Shaffi; Kaur, Taranjeet; Kumar, Sushil; Lakhanpal, Dinesh; Lakhman, Sukhwinder S; Kaur, Gurcharan

2015-12-01

Intermittent fasting dietary restriction (IF-DR) is recently reported to be an effective intervention to retard age associated disease load and to promote healthy aging. Since sustaining long term caloric restriction regimen is not practically feasible in humans, so use of alternate approach such as late onset short term IF-DR regimen which is reported to trigger similar biological pathways is gaining scientific interest. The current study was designed to investigate the effect of IF-DR regimen implemented for 12 weeks in middle age rats on their motor coordination skills and protein and DNA damage in different brain regions. Further, the effect of IF-DR regimen was also studied on expression of energy regulators, cell survival pathways and synaptic plasticity marker proteins. Our data demonstrate that there was an improvement in motor coordination and learning response with decline in protein oxidative damage and recovery in expression of energy regulating neuropeptides. We further observed significant downregulation in nuclear factor kappa B (NF-κB) and cytochrome c (Cyt c) levels and moderate upregulation of mortalin and synaptophysin expression. The present data may provide an insight on how a modest level of short term IF-DR, imposed in middle age, can slow down or prevent the age-associated impairment of brain functions and promote healthy aging by involving multiple regulatory pathways aimed at maintaining energy homeostasis.

Dietary management practices in phenylketonuria across European centres

DEFF Research Database (Denmark)

Ahring, Kirsten; Bélanger-Quintana, Amaya; Dokoupil, Katharina

2009-01-01

, and the definition of foods that could be eaten without restriction ('free foods'). Eighty percent (n=8/10) of centres encouraged breastfeeding together with protein substitute in infants with PKU. CONCLUSIONS: Important differences exist among centres across Europe in the dietary management of PKU, and in support...... systems designed to assist patients in managing their diets. Further studies are needed to compare different dietary treatments with the aim of identifying best practice to optimise phenylalanine control and dietary adherence....

Listening comprehension across the adult lifespan.

Science.gov (United States)

Sommers, Mitchell S; Hale, Sandra; Myerson, Joel; Rose, Nathan; Tye-Murray, Nancy; Spehar, Brent

2011-01-01

Although age-related declines in perceiving spoken language are well established, the primary focus of research has been on perception of phonemes, words, and sentences. In contrast, relatively few investigations have been directed at establishing the effects of age on the comprehension of extended spoken passages. Moreover, most previous work has used extreme-group designs in which the performance of a group of young adults is contrasted with that of a group of older adults and little if any information is available regarding changes in listening comprehension across the adult lifespan. Accordingly, the goals of the current investigation were to determine whether there are age differences in listening comprehension across the adult lifespan and, if so, whether similar trajectories are observed for age-related changes in auditory sensitivity and listening comprehension. This study used a cross-sectional lifespan design in which approximately 60 individuals in each of 7 decades, from age 20 to 89 yr (a total of 433 participants), were tested on three different measures of listening comprehension. In addition, we obtained measures of auditory sensitivity from all participants. Changes in auditory sensitivity across the adult lifespan exhibited the progressive high-frequency loss typical of age-related hearing impairment. Performance on the listening comprehension measures, however, demonstrated a very different pattern, with scores on all measures remaining relatively stable until age 65 to 70 yr, after which significant declines were observed. Follow-up analyses indicated that this same general pattern was observed across three different types of passages (lectures, interviews, and narratives) and three different question types (information, integration, and inference). Multiple regression analyses indicated that low-frequency pure-tone average was the single largest contributor to age-related variance in listening comprehension for individuals older than 65 yr, but

The long-term effects of a life-prolonging heat treatment on the Drosophila melanogaster transcriptome suggest that heat shock proteins extend lifespan

DEFF Research Database (Denmark)

Sarup, Pernille Merete; Sørensen, Peter; Loeschcke, Volker

2014-01-01

Heat-induced hormesis, i.e. the beneficial effect of mild heat-induced stress, increases the average lifespan of many organisms. This effect, which depends on the heat shock factor, decreases the log mortality rate weeks after the stress has ceased. To identify candidate genes that mediate......-treated flies. Several hsp70 probe sets were up-regulated 1.7–2-fold in the mildly stressed flies weeks after the last heat treatment (P shock protein, Hsp70, is reported to return to normal levels of expression shortly after heat stress. We...... conclude that the heat shock response, and Hsp70 in particular, may be central to the heat-induced increase in the average lifespan in flies that are exposed to mild heat stress early in life....

Calorie restriction hysteretically primes aging Saccharomyces cerevisiae toward more effective oxidative metabolism.

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Erich B Tahara

Full Text Available Calorie restriction (CR is an intervention known to extend the lifespan of a wide variety of organisms. In S. cerevisiae, chronological lifespan is prolonged by decreasing glucose availability in the culture media, a model for CR. The mechanism has been proposed to involve an increase in the oxidative (versus fermentative metabolism of glucose. Here, we measured wild-type and respiratory incompetent (ρ(0 S. cerevisiae biomass formation, pH, oxygen and glucose consumption, and the evolution of ethanol, glycerol, acetate, pyruvate and succinate levels during the course of 28 days of chronological aging, aiming to identify metabolic changes responsible for the effects of CR. The concomitant and quantitative measurements allowed for calculations of conversion factors between different pairs of substrates and products, maximum specific substrate consumption and product formation rates and maximum specific growth rates. Interestingly, we found that the limitation of glucose availability in CR S. cerevisiae cultures hysteretically increases oxygen consumption rates many hours after the complete exhaustion of glucose from the media. Surprisingly, glucose-to-ethanol conversion and cellular growth supported by glucose were not quantitatively altered by CR. Instead, we found that CR primed the cells for earlier, faster and more efficient metabolism of respiratory substrates, especially ethanol. Since lifespan-enhancing effects of CR are absent in respiratory incompetent ρ(0 cells, we propose that the hysteretic effect of glucose limitation on oxidative metabolism is central toward chronological lifespan extension by CR in this yeast.

Methionine restriction alters bone morphology and affects osteoblast differentiation

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Amadou Ouattara

2016-12-01

Full Text Available Methionine restriction (MR extends the lifespan of a wide variety of species, including rodents, drosophila, nematodes, and yeasts. MR has also been demonstrated to affect the overall growth of mice and rats. The objective of this study was to evaluate the effect of MR on bone structure in young and aged male and female C57BL/6J mice. This study indicated that MR affected the growth rates of males and young females, but not aged females. MR reduced volumetric bone mass density (vBMD and bone mineral content (BMC, while bone microarchitecture parameters were decreased in males and young females, but not in aged females compared to control-fed (CF mice. However, when adjusted for bodyweight, the effect of MR in reducing vBMD, BMC and microarchitecture measurements was either attenuated or reversed suggesting that the smaller bones in MR mice is appropriate for its body size. In addition, CF and MR mice had similar intrinsic strength properties as measured by nanoindentation. Plasma biomarkers suggested that the low bone mass in MR mice could be due to increased collagen degradation, which may be influenced by leptin, IGF-1, adiponectin and FGF21 hormone levels. Mouse preosteoblast cell line cultured under low sulfur amino acid growth media attenuated gene expression levels of Col1al, Runx2, Bglap, Alpl and Spp1 suggesting delayed collagen formation and bone differentiation. Collectively, our studies revealed that MR altered bone morphology which could be mediated by delays in osteoblast differentiation. Keywords: Methionine restriction, Aged mice, Micro-computed tomography, Nanoindentation, MC3T3-E1 subclone 4

In vitro investigation of cytochrome P450-mediated metabolism of dietary flavonoids

DEFF Research Database (Denmark)

Breinholt, Vibeke; Offord, E.A.; Brouwer, C.

2002-01-01

Human and mouse liver microsomes And membranes isolated from Escherichia coli, which expressed cytochrome P450 (CYP) 1A2, 3A4 2C9 or 2D6, were used to investigate CYP-mediated metabolism of five selected dietary flavonoids. In human and mouse liver microsomes kaempferol, apigenin and naringenin...... were hydroxylated at the 3'-position to yield their corresponding analogs quercetin, luteolin and eriodietyol, whereas hesperetin and tamarixetin were demethylated at the 4'-position to yield eriodictyol and quercetin. respectively, Microsomal flavonoid metabolism as potently inhibited by the CYP1A2...... inhibitors. fluvoxamine and alpha-naphthoflavone. Recombinant CYP1A2 as capable of metabolizing all five investigated flavonoids. CYP3A4 recombinant protein did not catalyze hesperetin demethylation. but showed similar metabolic profiles for the remaining compounds, as did human microsomes and recombinant...

Why do lifespan variability trends for the young and old diverge? A perturbation analysis

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Michal Engelman

2014-05-01

Full Text Available Background: Variation in lifespan has followed strikingly different trends for the young and old: while overall lifespan variability has decreased as life expectancy at birth has risen, the variability conditional on survival to older ages has increased. These diverging trends reflect changes in the underlying demographic parameters determining age-specific mortality. Objective: We ask why the variation in the adult ages at death has followed a different trend than the variation at younger ages, and aim to explain the diverging patterns in terms of historical changes in the age schedule of mortality. Methods: Using simulations, we show that the empirical trends in lifespan variation are well characterized using the Siler model, which describes the mortality hazard across the full lifespan using functions representing early-life, later-life, and background mortality. We then obtain maximum likelihood estimates of the Siler parameters over time. Finally, we express lifespan variation in terms of a Markov chain model, and apply matrix calculus perturbation analysis to compute the sensitivity of age-specific lifespan variance trends to the changing Siler model parameters. Results: Our analysis produces a detailed quantification of the impact of changing demographic parameters on the pattern of lifespan variability at all ages, highlighting the impact of declining childhood mortality on the reduction of lifespan variability and the impact of improved survival in adulthood on the rising variability of lifespans at older ages. Conclusions: These findings provide insight into the dynamic relationship between the age pattern of survival improvements and time trends in lifespan variability.

Maintenance of cellular ATP level by caloric restriction correlates chronological survival of budding yeast

International Nuclear Information System (INIS)

Choi, Joon-Seok; Lee, Cheol-Koo

2013-01-01

Highlights: •CR decreases total ROS and mitochondrial superoxide during the chronological aging. •CR does not affect the levels of oxidative damage on protein and DNA. •CR contributes extension of chronological lifespan by maintenance of ATP level -- Abstract: The free radical theory of aging emphasizes cumulative oxidative damage in the genome and intracellular proteins due to reactive oxygen species (ROS), which is a major cause for aging. Caloric restriction (CR) has been known as a representative treatment that prevents aging; however, its mechanism of action remains elusive. Here, we show that CR extends the chronological lifespan (CLS) of budding yeast by maintaining cellular energy levels. CR reduced the generation of total ROS and mitochondrial superoxide; however, CR did not reduce the oxidative damage in proteins and DNA. Subsequently, calorie-restricted yeast had higher mitochondrial membrane potential (MMP), and it sustained consistent ATP levels during the process of chronological aging. Our results suggest that CR extends the survival of the chronologically aged cells by improving the efficiency of energy metabolism for the maintenance of the ATP level rather than reducing the global oxidative damage of proteins and DNA

Maintenance of cellular ATP level by caloric restriction correlates chronological survival of budding yeast

Energy Technology Data Exchange (ETDEWEB)

Choi, Joon-Seok; Lee, Cheol-Koo, E-mail: cklee2005@korea.ac.kr

2013-09-13

Highlights: •CR decreases total ROS and mitochondrial superoxide during the chronological aging. •CR does not affect the levels of oxidative damage on protein and DNA. •CR contributes extension of chronological lifespan by maintenance of ATP level -- Abstract: The free radical theory of aging emphasizes cumulative oxidative damage in the genome and intracellular proteins due to reactive oxygen species (ROS), which is a major cause for aging. Caloric restriction (CR) has been known as a representative treatment that prevents aging; however, its mechanism of action remains elusive. Here, we show that CR extends the chronological lifespan (CLS) of budding yeast by maintaining cellular energy levels. CR reduced the generation of total ROS and mitochondrial superoxide; however, CR did not reduce the oxidative damage in proteins and DNA. Subsequently, calorie-restricted yeast had higher mitochondrial membrane potential (MMP), and it sustained consistent ATP levels during the process of chronological aging. Our results suggest that CR extends the survival of the chronologically aged cells by improving the efficiency of energy metabolism for the maintenance of the ATP level rather than reducing the global oxidative damage of proteins and DNA.

Altered gut microbiota in female mice with persistent low body weights following removal of post-weaning chronic dietary restriction.

Science.gov (United States)

Chen, Jun; Toyomasu, Yoshitaka; Hayashi, Yujiro; Linden, David R; Szurszewski, Joseph H; Nelson, Heidi; Farrugia, Gianrico; Kashyap, Purna C; Chia, Nicholas; Ordog, Tamas

2016-10-03

Nutritional interventions often fail to prevent growth failure in childhood and adolescent malnutrition and the mechanisms remain unclear. Recent studies revealed altered microbiota in malnourished children and anorexia nervosa. To facilitate mechanistic studies under physiologically relevant conditions, we established a mouse model of growth failure following chronic dietary restriction and examined microbiota in relation to age, diet, body weight, and anabolic treatment. Four-week-old female BALB/c mice (n = 12/group) were fed ad libitum (AL) or offered limited food to abolish weight gain (LF). A subset of restricted mice was treated with an insulin-like growth factor 1 (IGF1) analog. Food access was restored in a subset of untreated LF (LF-RF) and IGF1-treated LF mice (TLF-RF) on day 97. Gut microbiota were determined on days 69, 96-99 and 120 by next generation sequencing of the V3-5 region of the 16S rRNA gene. Microbiota-host factor associations were analyzed by distance-based PERMANOVA and quantified by the coefficient of determination R 2 for age, diet, and normalized body weight change (Δbwt). Microbial taxa on day 120 were compared following fitting with an overdispersed Poisson regression model. The machine learning algorithm Random Forests was used to predict age based on the microbiota. On day 120, Δbwt in AL, LF, LF-RF, and TLF-RF mice was 52 ± 3, -6 ± 1*, 40 ± 3*, and 46 ± 2 % (*, P < 0.05 versus AL). Age and diet, but not Δbwt, were associated with gut microbiota composition. Age explained a larger proportion of the microbiota variability than diet or Δbwt. Random Forests predicted chronological age based on the microbiota and indicated microbiota immaturity in the LF mice before, but not after, refeeding. However, on day 120, the microbiota community structure of LF-RF mice was significantly different from that of both AL and LF mice. IGF1 mitigated the difference from the AL group. Refed groups had a higher

The Effect of Moderate Dietary Protein and Phosphate Restriction on Calcium-Phosphate Homeostasis in Healthy Older Cats.

Science.gov (United States)

Geddes, R F; Biourge, V; Chang, Y; Syme, H M; Elliott, J

2016-09-01

Dietary phosphate and protein restriction decreases plasma PTH and FGF-23 concentrations and improves survival time in azotemic cats, but has not been examined in cats that are not azotemic. Feeding a moderately protein- and phosphate-restricted diet decreases PTH and FGF-23 in healthy older cats and thereby slows progression to azotemic CKD. A total of 54 healthy, client-owned cats (≥ 9 years). Prospective double-blinded randomized placebo-controlled trial. Cats were assigned to test diet (protein 76 g/Mcal and phosphate 1.6 g/Mcal) or control diet (protein 86 g/Mcal and phosphate 2.6 g/Mcal) and monitored for 18 months. Changes in variables over time and effect of diet were assessed by linear mixed models. A total of 26 cats ate test diet and 28 cats ate control diet. There was a significant effect of diet on urinary fractional excretion of phosphate (P = 0.045), plasma PTH (P = 0.005), and ionized calcium concentrations (P = 0.018), but not plasma phosphate, FGF-23, or creatinine concentrations. Plasma PTH concentrations did not significantly change in cats fed the test diet (P = 0.62) but increased over time in cats fed the control diet (P = 0.001). There was no significant treatment effect of the test diet on development of azotemic CKD (3 of 26 (12%) test versus 3 of 28 (11%) control, odds ratio 1.09 (95% CI 0.13-8.94), P = 0.92). Feeding a moderately protein- and phosphate-restricted diet has effects on calcium-phosphate homeostasis in healthy older cats and is well tolerated. This might have an impact on renal function and could be useful in early chronic kidney disease. Copyright © 2016 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

Assimilation of endogenous nicotinamide riboside is essential for calorie restriction-mediated life span extension in Saccharomyces cerevisiae.

Science.gov (United States)

Lu, Shu-Ping; Kato, Michiko; Lin, Su-Ju

2009-06-19

NAD(+) (nicotinamide adenine dinucleotide) is an essential cofactor involved in various biological processes including calorie restriction-mediated life span extension. Administration of nicotinamide riboside (NmR) has been shown to ameliorate deficiencies related to aberrant NAD(+) metabolism in both yeast and mammalian cells. However, the biological role of endogenous NmR remains unclear. Here we demonstrate that salvaging endogenous NmR is an integral part of NAD(+) metabolism. A balanced NmR salvage cycle is essential for calorie restriction-induced life span extension and stress resistance in yeast. Our results also suggest that partitioning of the pyridine nucleotide flux between the classical salvage cycle and the NmR salvage branch might be modulated by the NAD(+)-dependent Sir2 deacetylase. Furthermore, two novel deamidation steps leading to nicotinic acid mononucleotide and nicotinic acid riboside production are also uncovered that further underscore the complexity and flexibility of NAD(+) metabolism. In addition, utilization of extracellular nicotinamide mononucleotide requires prior conversion to NmR mediated by a periplasmic phosphatase Pho5. Conversion to NmR may thus represent a strategy for the transport and assimilation of large nonpermeable NAD(+) precursors. Together, our studies provide a molecular basis for how NAD(+) homeostasis factors confer metabolic flexibility.

Impacts of Dietary Phytochemicals in the Presence and Absence of Pesticides on Longevity of Honey Bees (Apis mellifera

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Ling-Hsiu Liao

2017-02-01

Full Text Available Because certain flavonols and phenolic acids are found in pollen and nectar of most angiosperms, they are routinely ingested by Apis mellifera, the western honey bee. The flavonol quercetin and the phenolic acid p-coumaric acid are known to upregulate detoxification enzymes in adult bees; their presence or absence in the diet may thus affect the toxicity of ingested pesticides. We conducted a series of longevity assays with one-day-old adult workers to test if dietary phytochemicals enhance longevity and pesticide tolerance. One-day-old bees were maintained on sugar syrup with or without casein (a phytochemical-free protein source in the presence or absence of quercetin and p-coumaric acid as well as in the presence or absence of two pyrethroid insecticides, bifenthrin and β-cyfluthrin. Dietary quercetin (hazard ratio, HR = 0.82, p-coumaric acid (HR = 0.91 and casein (HR = 0.74 were associated with extended lifespan and the two pyrethroid insecticides, 4 ppm bifenthrin (HR = 9.17 and 0.5 ppm β-cyfluthrin (HR = 1.34, reduced lifespan. Dietary quercetin enhanced tolerance of both pyrethroids; p-coumaric acid had a similar effect trend, although of reduced magnitude. Casein in the diet appears to eliminate the life-prolonging effect of p-coumaric acid in the absence of quercetin. Collectively, these assays demonstrate that dietary phytochemicals influence honey bee longevity and pesticide stress; substituting sugar syrups for honey or yeast/soy flour patties may thus have hitherto unrecognized impacts on adult bee health.

Dietary phosphate restriction normalizes biochemical and skeletal abnormalities in a murine model of tumoral calcinosis.

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Ichikawa, Shoji; Austin, Anthony M; Gray, Amie K; Allen, Matthew R; Econs, Michael J

2011-12-01

Mutations in the GALNT3 gene cause tumoral calcinosis characterized by ectopic calcifications due to persistent hyperphosphatemia. We recently developed Galnt3 knockout mice in a mixed background, which had hyperphosphatemia with increased bone mineral density (BMD) and infertility in males. To test the effect of dietary phosphate intake on their phenotype, Galnt3 knockout mice were generated in the C57BL/6J strain and fed various phosphate diets: 0.1% (low), 0.3% (low normal), 0.6% (normal), and 1.65% (high). Sera were analyzed for calcium, phosphorus, alkaline phosphatase, creatinine, blood urine nitrogen, 1,25-dihydroxyvitamin D, osteocalcin, tartrate-resistant acid phosphatase 5b, and fibroblast growth factor 23 (Fgf23). Femurs were evaluated by dual-energy x-ray absorptiometry, dynamic histomorphometry, and/or microcomputed tomography. Galnt3 knockout mice in C57BL/6J had the same biochemical phenotype observed in our previous study: hyperphosphatemia, inappropriately normal 1,25-dihydroxyvitamin D level, decreased alkaline phosphatase activity, and low intact Fgf23 concentration but high Fgf23 fragments. Skeletal analyses of their femurs revealed significantly high BMD with increased cortical bone area and trabecular bone volume. On all four phosphate diets, Galnt3 knockout mice had consistently higher phosphorus levels and lower alkaline phosphatase and intact Fgf23 concentrations than littermate controls. The low-phosphate diet normalized serum phosphorus, alkaline phosphatase, and areal BMD but failed to correct male infertility in Galnt3 knockout mice. The high-phosphate diet did not increase serum phosphorus concentration in either mutant or control mice due to a compensatory increase in circulating intact Fgf23 levels. In conclusion, dietary phosphate restriction normalizes biochemical and skeletal phenotypes of Galnt3 knockout mice and, thus, can be an effective therapy for tumoral calcinosis.

Food restriction prevents an age-associated increase in rat liver beta-adrenergic receptors

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Dax, E.M.; Ingram, D.K.; Partilla, J.S.; Gregerman, R.I.

1989-05-01

In male Wistar rats fed ad libitum (24% protein, 4.5 Kcal/gm), the (/sup 125/I)iodopindolol binding capacity of the beta-adrenergic receptors in liver of 24-month-old animals is 3-4 times greater than that of 6-month-old counterparts. In rats fed the same diet, on alternate days from weaning, the receptor capacity did not increase significantly between 6 and 24 months (10.20 +/- 0.55 vs 9.20 +/- 0.72 fmol/mg) or between 24 and 30 months. This was not due to acute dietary deprivation, as rats food-restricted for only 2 weeks, at 23.5 months of age, also showed elevated receptor capacities compared to 6-month-old ad libitum fed animals. Moreover, intermittent feeding produced no significant effects among 6-month-old animals, whether restricted since weaning or for two weeks prior to sacrifice. Many biochemical parameters that decrease with aging in rats fed ad libitum are prevented by dietary restriction. Our results demonstrate that a reproducible biochemical process that increases with aging is also prevented with dietary restriction. The age-related, liver beta-receptor increase may be a potentially reliable marker for studying biochemical perturbations that modify life span.

Food restriction prevents an age-associated increase in rat liver beta-adrenergic receptors

International Nuclear Information System (INIS)

Dax, E.M.; Ingram, D.K.; Partilla, J.S.; Gregerman, R.I.

1989-01-01

In male Wistar rats fed ad libitum (24% protein, 4.5 Kcal/gm), the [ 125 I]iodopindolol binding capacity of the beta-adrenergic receptors in liver of 24-month-old animals is 3-4 times greater than that of 6-month-old counterparts. In rats fed the same diet, on alternate days from weaning, the receptor capacity did not increase significantly between 6 and 24 months (10.20 +/- 0.55 vs 9.20 +/- 0.72 fmol/mg) or between 24 and 30 months. This was not due to acute dietary deprivation, as rats food-restricted for only 2 weeks, at 23.5 months of age, also showed elevated receptor capacities compared to 6-month-old ad libitum fed animals. Moreover, intermittent feeding produced no significant effects among 6-month-old animals, whether restricted since weaning or for two weeks prior to sacrifice. Many biochemical parameters that decrease with aging in rats fed ad libitum are prevented by dietary restriction. Our results demonstrate that a reproducible biochemical process that increases with aging is also prevented with dietary restriction. The age-related, liver beta-receptor increase may be a potentially reliable marker for studying biochemical perturbations that modify life span

Muscle-Specific Histone H3K36 Dimethyltransferase SET-18 Shortens Lifespan of Caenorhabditis elegans by Repressing daf-16a Expression

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Liangping Su

2018-03-01

Full Text Available Mounting evidence shows that histone methylation, a typical epigenetic mark, is crucial for gene expression regulation during aging. Decreased trimethylation of Lys 36 on histone H3 (H3K36me3 in worms and yeast is reported to shorten lifespan. The function of H3K36me2 in aging remains unclear. In this study, we identified Caenorhabditis elegans SET-18 as a histone H3K36 dimethyltransferase. SET-18 deletion extended lifespan and increased oxidative stress resistance, dependent on daf-16 activity in the insulin/IGF pathway. In set-18 mutants, transcription of daf-16 isoform a (daf-16a was specifically upregulated. Accordingly, a decrease in H3K36me2 on daf-16a promoter was observed. Muscle-specific expression of SET-18 increased in aged worms (day 7 and day 11, attributable to elevation of global H3K36me2 and inhibition of daf-16a expression. Consequently, longevity was shortened. These findings suggested that chromatic repression mediated by tissue-specific H3K36 dimethyltransferase might be detrimental to lifespan and may have implications in human age-related diseases.

Understanding retirement: the promise of life-span developmental frameworks.

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Löckenhoff, Corinna E

2012-09-01

The impending retirement of large population cohorts creates a pressing need for practical interventions to optimize outcomes at the individual and societal level. This necessitates comprehensive theoretical models that acknowledge the multi-layered nature of the retirement process and shed light on the dynamic mechanisms that drive longitudinal patterns of adjustment. The present commentary highlights ways in which contemporary life-span developmental frameworks can inform retirement research, drawing on the specific examples of Bronfenbrenner's Ecological Model, Baltes and Baltes Selective Optimization with Compensation Framework, Schulz and Heckhausen's Motivational Theory of Life-Span Development, and Carstensen's Socioemotional Selectivity Theory. Ultimately, a life-span developmental perspective on retirement offers not only new interpretations of known phenomena but may also help to identify novel directions for future research as well as promising pathways for interventions.

A low-fat, whole-food vegan diet, as well as other strategies that down-regulate IGF-I activity, may slow the human aging process.

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McCarty, Mark F

2003-06-01

A considerable amount of evidence is consistent with the proposition that systemic IGF-I activity acts as pacesetter in the aging process. A reduction in IGF-I activity is the common characteristic of rodents whose maximal lifespan has been increased by a wide range of genetic or dietary measures, including caloric restriction. The lifespans of breeds of dogs and strains of rats tend to be inversely proportional to their mature weight and IGF-I levels. The link between IGF-I and aging appears to be evolutionarily conserved; in worms and flies, lifespan is increased by reduction-of-function mutations in signaling intermediates homologous to those which mediate insulin/IGF-I activity in mammals. The fact that an increase in IGF-I activity plays a key role in the induction of sexual maturity, is consistent with a broader role for-IGF-I in aging regulation. If down-regulation of IGF-I activity could indeed slow aging in humans, a range of practical measures for achieving this may be at hand. These include a low-fat, whole-food, vegan diet, exercise training, soluble fiber, insulin sensitizers, appetite suppressants, and agents such as flax lignans, oral estrogen, or tamoxifen that decrease hepatic synthesis of IGF-I. Many of these measures would also be expected to decrease risk for common age-related diseases. Regimens combining several of these approaches might have a sufficient impact on IGF-I activity to achieve a useful retardation of the aging process. However, in light of the fact that IGF-I promotes endothelial production of nitric oxide and may be of especial importance to cerebrovascular health, additional measures for stroke prevention-most notably salt restriction-may be advisable when attempting to down-regulate IGF-I activity as a pro-longevity strategy.

Bowel preparation in CT colonography. Is diet restriction necessary? A randomised trial (DIETSAN)

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Bellini, Davide; De Santis, Domenico; Caruso, Damiano; Rengo, Marco; Biondi, Tommaso; Laghi, Andrea [Rome Univ. ' ' Sapienza' ' (Italy). Dept. of Radiological Sciences, Oncology and Pathology; I.C.O.T. Hospital, Latina (Italy); Ferrari, Riccardo [San Camillo Forlanini Hospital, Rome (Italy). Dept. of Emergency Radiology

2018-01-15

To investigate whether diet restriction affects quality of colon cleansing and patient tolerance during reduced bowel preparation for CT colonography (CTC). Asymptomatic and symptomatic patients were enrolled in this pragmatic, single-centre, randomised trial. All patients were randomly assigned (1:1 ratio, blocks of ten) to receive a reduced bowel preparation and faecal tagging with (Diet-Restriction-Group [DR]) or without (No-Diet-Restriction-Group [NDR]) dietary restriction. Five readers performed a blinded subjective image analysis, by means of 4-point Likert-scales from 0 (highest score) to 3 (worst score). Endpoints were the quality of large bowel cleansing and tolerance to the assigned bowel preparation regimen. The trial is registered at ClinicalTrial.gov (URomLSDBAL1). Ninety-five patients were randomly allocated to treatments (48 in NDR-group, 47 in DR-group). Both groups resulted in optimal colon cleansing. The mean residual stool (0.22, 95%CI 0.00-0.44) and fluid burden (0.39, 95%CI 0.25-0.53) scores for patients in DR-group were similar to those in patients in NDR-group (0.25, 95%CI 0.03-0.47 [p = 0.82] and 0.49, 95%CI 0.30-0.67 [p = 0.38], respectively). Tolerance was significantly better in NDR-group. A reduced bowel preparation in association with faecal tagging and without any dietary restriction demonstrated optimal colon cleansing effectiveness for CTC, providing better patient compliance compared with dietary restriction. (orig.)

Bowel preparation in CT colonography. Is diet restriction necessary? A randomised trial (DIETSAN)

International Nuclear Information System (INIS)

Bellini, Davide; De Santis, Domenico; Caruso, Damiano; Rengo, Marco; Biondi, Tommaso; Laghi, Andrea; Ferrari, Riccardo

2018-01-01

To investigate whether diet restriction affects quality of colon cleansing and patient tolerance during reduced bowel preparation for CT colonography (CTC). Asymptomatic and symptomatic patients were enrolled in this pragmatic, single-centre, randomised trial. All patients were randomly assigned (1:1 ratio, blocks of ten) to receive a reduced bowel preparation and faecal tagging with (Diet-Restriction-Group [DR]) or without (No-Diet-Restriction-Group [NDR]) dietary restriction. Five readers performed a blinded subjective image analysis, by means of 4-point Likert-scales from 0 (highest score) to 3 (worst score). Endpoints were the quality of large bowel cleansing and tolerance to the assigned bowel preparation regimen. The trial is registered at ClinicalTrial.gov (URomLSDBAL1). Ninety-five patients were randomly allocated to treatments (48 in NDR-group, 47 in DR-group). Both groups resulted in optimal colon cleansing. The mean residual stool (0.22, 95%CI 0.00-0.44) and fluid burden (0.39, 95%CI 0.25-0.53) scores for patients in DR-group were similar to those in patients in NDR-group (0.25, 95%CI 0.03-0.47 [p = 0.82] and 0.49, 95%CI 0.30-0.67 [p = 0.38], respectively). Tolerance was significantly better in NDR-group. A reduced bowel preparation in association with faecal tagging and without any dietary restriction demonstrated optimal colon cleansing effectiveness for CTC, providing better patient compliance compared with dietary restriction. (orig.)

The Path to Competence: A Lifespan Developmental Perspective on Reading

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Alexander, Patricia A.

2012-01-01

The purpose of this document is to present a developmental model of reading that encompasses changes across the lifespan. The need for such a lifespan orientation toward reading within our educational institutions is great. Until we adopt this lifelong perspective, we continue to run the risk of turning out undeveloped, unmotivated, and uncritical…

Lifelong dietary intervention does not affect hematopoietic stem cell function

NARCIS (Netherlands)

Lazare, Seka; Ausema, Albertina; Reijne, Aaffien C; van Dijk, Gertjan; van Os, Ronald; de Haan, Gerald

Hematopoietic stem cells (HSCs) undergo a profound functional decline during normal aging. Because caloric or dietary restriction has been shown to delay multiple aspects of the aging process in many species, we explored the consequences of lifelong caloric restriction, or conversely, lifelong

Association between duration of reproductive lifespan and Framingham risk score in postmenopausal women.

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Kim, Soo Hyun; Sim, Mu Yul; Park, Sat Byul

2015-12-01

The benefit of estrogen therapy in postmenopausal women is still uncertain. Based upon extensive observational data, it was believed that estrogen was cardioprotective. The relationship between the period of exposure to endogenous estrogens and the risk of cardiovascular disease (CVD) has not been studied in Korean women. To assess associations between reproductive lifespan and CVD by using the Framingham risk score (FRS) in postmenopausal Korean women. This cross-sectional, population-based study used data from the Korea National Health and Nutrition Examination Survey (KNHANES) for the five years 2008-2012,after adjustment for relevant variables using complex sample analysis and data weighting. Among 25,534 women, 1973 women were enrolled, after excluding those 80 years of age (n=6194), those with diabetes, CVD or cancer (n=491), those with unrecorded physical measurements (n=7335), those with menarche age ≤8 years or ≥20 years (n=6194), and premenopausal women (n=3347). The FRS tended to show a significant negative correlation with the reproductive lifespan (preproductive lifespan and FRS (adjusted relative risk [RR] for reproductive years [shortest lifespan group] compared with 28-33 reproductive years [moderate lifespan group], 1.2, p33 reproductive years [longest lifespan group] compared with 28-33 reproductive years [moderate lifespan group], -0.42, p=0.011). A longer reproductive lifespan is associated with a lower estimated risk of CVD in the next 10 years in postmenopausal women. This result suggests that estrogen has a long-term protective effect against CVD. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Extension of mouse lifespan by overexpression of catalase.

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Schriner, Samuel E; Linford, Nancy J

2006-06-01

The free radical theory of aging was originally proposed 50 years ago, and is arguably the most popular mechanism explaining the aging process. According to this theory, aging results from the progressive decline in organ function due to the damage generated by reactive oxygen species (ROS). These chemical species are a normal part of metabolism, and a group of enzymes exists to protect cells against their toxic effects. One of these species is hydrogen peroxide (H(2)O(2)), which can be degraded by catalase. To determine the role of hydrogen peroxide in aging and its importance in different subcellular compartments, transgenic mice were developed with increased catalase activities localized to the peroxisome (PCAT), nucleus (NCAT), or mitochondrion (MCAT). The largest effect on lifespan was found in MCAT animals, with a 20% increase in median lifespan and a 10% increase in the maximum lifespan. A more modest effect was seen in PCAT animals, and no significant change was found in NCAT animals. Upon further examination of the MCAT mice, it was found that H(2)O(2) production and H(2)O(2)-induced aconitase inactivation were attenuated, oxidative damage and the development of mitochondrial deletions were reduced, and cardiac pathology and cataract development were delayed. These results are consistent with a role of H(2)O(2) in the development of pathology and in the limitation of mouse lifespan. They also demonstrate the importance of mitochondria as a source, and possible target, of ROS.

Towards a unified analysis of brain maturation and aging across the entire lifespan: A MRI analysis.

Science.gov (United States)

Coupé, Pierrick; Catheline, Gwenaelle; Lanuza, Enrique; Manjón, José Vicente

2017-11-01

There is no consensus in literature about lifespan brain maturation and senescence, mainly because previous lifespan studies have been performed on restricted age periods and/or with a limited number of scans, making results instable and their comparison very difficult. Moreover, the use of nonharmonized tools and different volumetric measurements lead to a great discrepancy in reported results. Thanks to the new paradigm of BigData sharing in neuroimaging and the last advances in image processing enabling to process baby as well as elderly scans with the same tool, new insights on brain maturation and aging can be obtained. This study presents brain volume trajectory over the entire lifespan using the largest age range to date (from few months of life to elderly) and one of the largest number of subjects (N = 2,944). First, we found that white matter trajectory based on absolute and normalized volumes follows an inverted U-shape with a maturation peak around middle life. Second, we found that from 1 to 8-10 y there is an absolute gray matter (GM) increase related to body growth followed by a GM decrease. However, when normalized volumes were considered, GM continuously decreases all along the life. Finally, we found that this observation holds for almost all the considered subcortical structures except for amygdala which is rather stable and hippocampus which exhibits an inverted U-shape with a longer maturation period. By revealing the entire brain trajectory picture, a consensus can be drawn since most of the previously discussed discrepancies can be explained. Hum Brain Mapp 38:5501-5518, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Landfill Lifespan Estimation: A Case Study

African Journals Online (AJOL)

Michael

2017-12-02

Dec 2, 2017 ... site selection, design, construction, operation and management. For this reason, it ... This research used the future value of money equation to estimate the lifespan of the ..... Geomatic Engineering, UMaT, Tarkwa, Ghana, pp.

Dietary Restriction Affects Neuronal Response Property and GABA Synthesis in the Primary Visual Cortex.

Directory of Open Access Journals (Sweden)

Jinfang Yang

Full Text Available Previous studies have reported inconsistent effects of dietary restriction (DR on cortical inhibition. To clarify this issue, we examined the response properties of neurons in the primary visual cortex (V1 of DR and control groups of cats using in vivo extracellular single-unit recording techniques, and assessed the synthesis of inhibitory neurotransmitter GABA in the V1 of cats from both groups using immunohistochemical and Western blot techniques. Our results showed that the response of V1 neurons to visual stimuli was significantly modified by DR, as indicated by an enhanced selectivity for stimulus orientations and motion directions, decreased visually-evoked response, lowered spontaneous activity and increased signal-to-noise ratio in DR cats relative to control cats. Further, it was shown that, accompanied with these changes of neuronal responsiveness, GABA immunoreactivity and the expression of a key GABA-synthesizing enzyme GAD67 in the V1 were significantly increased by DR. These results demonstrate that DR may retard brain aging by increasing the intracortical inhibition effect and improve the function of visual cortical neurons in visual information processing. This DR-induced elevation of cortical inhibition may favor the brain in modulating energy expenditure based on food availability.

Worker lifespan is an adaptive trait during colony establishment in the long-lived ant Lasius niger

NARCIS (Netherlands)

Kramer, Boris H.; Schaible, Ralf; Scheuerlein, Alexander

2016-01-01

Eusociality has been recognized as a strong driver of lifespan evolution. While queens show extraordinary lifespans of 20 years and more, worker lifespan is short and variable. A recent comparative study found that in eusocial species with larger average colony sizes the disparities in the lifespans

Obesity Exposure Across the Lifespan on Ovarian Cancer Pathogenesis

Science.gov (United States)

2015-08-01

exposure to the HFD or LFD, obese mice weighed significantly greater than lean mice (p=0.003, Table 1). There was no effect of HFD on non- fasted blood...AWARD NUMBER: W81XWH-13-1-0164 TITLE: Obesity Exposure Across the Lifespan on Ovarian Cancer Pathogenesis PRINCIPAL INVESTIGATOR: Victoria Bae...31 May 2015 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Obesity Exposure Across the Lifespan on Ovarian Cancer Pathogenesis 5b. GRANT NUMBER

Insulin signaling and dietary restriction differentially influence the decline of learning and memory with age.

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Amanda L Kauffman

2010-05-01

Full Text Available Of all the age-related declines, memory loss is one of the most devastating. While conditions that increase longevity have been identified, the effects of these longevity-promoting factors on learning and memory are unknown. Here we show that the C. elegans Insulin/IGF-1 receptor mutant daf-2 improves memory performance early in adulthood and maintains learning ability better with age but, surprisingly, demonstrates no extension in long-term memory with age. By contrast, eat-2 mutants, a model of Dietary Restriction (DR, exhibit impaired long-term memory in young adulthood but maintain this level of memory longer with age. We find that crh-1, the C. elegans homolog of the CREB transcription factor, is required for long-term associative memory, but not for learning or short-term memory. The expression of crh-1 declines with age and differs in the longevity mutants, and CREB expression and activity correlate with memory performance. Our results suggest that specific longevity treatments have acute and long-term effects on cognitive functions that decline with age through their regulation of rate-limiting genes required for learning and memory.

Cancer Chemoprevention by Traditional Chinese Herbal Medicine and Dietary Phytochemicals: Targeting Nrf2-Mediated Oxidative Stress/Anti-Inflammatory Responses, Epigenetics, and Cancer Stem Cells

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Jong Hun Lee

2013-01-01

Full Text Available Excessive oxidative stress induced by reactive oxygen species (ROS, reactive nitrogen species (RNS, and reactive metabolites of carcinogens alters cellular homeostasis, leading to genetic/epigenetic changes, genomic instability, neoplastic transformation, and cancer initiation/progression. As a protective mechanism against oxidative stress, antioxidant/detoxifying enzymes reduce these reactive species and protect normal cells from endo-/exogenous oxidative damage. The transcription factor nuclear factor-erythroid 2 p45 (NF-E2-related factor 2 (Nrf2, a master regulator of the antioxidative stress response, plays a critical role in the expression of many cytoprotective enzymes, including NAD(PH:quinine oxidoreductase (NQO1, heme oxygenase-1 (HO-1, UDP-glucuronosyltransferase (UGT, and glutathione S-transferase (GST. Recent studies demonstrated that many dietary phytochemicals derived from various vegetables, fruits, spices, and herbal medicines induce Nrf2-mediated antioxidant/detoxifying enzymes, restore aberrant epigenetic alterations, and eliminate cancer stem cells (CSCs. The Nrf2-mediated antioxidant response prevents many age-related diseases, including cancer. Owing to their fundamental contribution to carcinogenesis, epigenetic modifications and CSCs are novel targets of dietary phytochemicals and traditional Chinese herbal medicine (TCHM. In this review, we summarize cancer chemoprevention by dietary phytochemicals, including TCHM, which have great potential as a safer and more effective strategy for preventing cancer.

The efficacy of the appetite suppressant, diethylpropion, is dependent on both when it is given (day vs. night) and under conditions of high fat dietary restriction.

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Kalyanasundar, B; Solorio, Jessica; Perez, Claudia I; Hoyo-Vadillo, Carlos; Simon, Sidney A; Gutierrez, Ranier

2016-05-01

Obesity is a public health problem caused by excessive consumption of high caloric diets and/or lack of physical activity. Although treatments for obesity include low caloric diets and exercise programs, these activities frequently are supplemented with appetite suppressants. For the short-term treatment of weight loss, diethylpropion (DEP) is a commonly used appetite suppressant. However, little is known with regard to how to improve its weight loss efficacy. We therefore evaluated, in rats, two administration protocols where the animals received daily injections of DEP. First, when these nocturnal animals were normally active (at night) and when they were normally inactive (daytime), and second, with or without high fat dietary restriction (HFDR). We observed that DEP induced a greater weight-loss administered when the animals were in their active phase than in their inactive phase. Moreover, DEP's administration during the inactive phase (and to a lesser degree in the active phase) promotes the consumption of food during normal sleeping time. In addition, we found that DEP-induced weight loss under ad libitum access to a HF diet, but its efficacy significantly improved under conditions of HFDR. In summary, the efficacy of DEP, and presumably other like appetite suppressants, is enhanced by carefully controlling the time it is administered and under dietary restriction of HF diets. Copyright © 2016 Elsevier Ltd. All rights reserved.

Parental mediation and cyberbullying - a longitudinal study.

Science.gov (United States)

Chng, Grace S; Liau, Albert; Khoo, Angeline; Li, Dongdong

2014-01-01

Parents use active and restrictive mediation strategies to guide and regulate children's online participation and the online risks they encounter. However, changes in parental mediation do occur over time and the effectiveness of these strategies on cyberbullying demands for further empirical investigation. The current study addresses these issues with a sample of 1084 students (49% girls) in a longitudinal, three-wave design. Gender differences were tested via multi-group analyses. Longitudinal growth models showed that parental use of both active and restrictive mediation decreased over time. For both types of mediation, the mean rate of change had a significant effect on boys' engagement in cyberbullying, but not for girls. Initial levels of restrictive mediation, but not active mediation, were found to be significantly predictive of cyberbullying in both genders. Girls had higher initial levels of both parental mediation types in comparison to boys. The results reveal that the effectiveness of active and restrictive mediation in relation to students' cyberbullying differs and informs us on gender differences. The implications of these results for parental education in online mediation are discussed.

Telomeres and the natural lifespan limit in humans

DEFF Research Database (Denmark)

Steenstrup, Troels; Kark, Jeremy D; Verhulst, Simon

2017-01-01

An ongoing debate in demography has focused on whether the human lifespan has a maximal natural limit. Taking a mechanistic perspective, and knowing that short telomeres are associated with diminished longevity, we examined whether telomere length dynamics during adult life could set a maximal...... natural lifespan limit. We define leukocyte telomere length of 5 kb as the 'telomeric brink', which denotes a high risk of imminent death. We show that a subset of adults may reach the telomeric brink within the current life expectancy and more so for a 100-year life expectancy. Thus, secular trends...

Sex differences in the genetic architecture of lifespan in a seed beetle: extreme inbreeding extends male lifespan

DEFF Research Database (Denmark)

Bilde, T.; Maklakov, Alexei A.; Meisner, Katrine

2009-01-01

Background Sex differences in lifespan are ubiquitous throughout the animal kingdom but the causes underlying this phenomenon remain poorly understood. Several explanations based on asymmetrical inheritance patterns (sex chromosomes or mitochondrial DNA) have been proposed, but these ideas have...

Muscle-Specific Histone H3K36 Dimethyltransferase SET-18 Shortens Lifespan of Caenorhabditis elegans by Repressing daf-16a Expression.

Science.gov (United States)

Su, Liangping; Li, Hongyuan; Huang, Cheng; Zhao, Tingting; Zhang, Yongjun; Ba, Xueqing; Li, Zhongwei; Zhang, Yu; Huang, Baiqu; Lu, Jun; Zhao, Yanmei; Li, Xiaoxue

2018-03-06

Mounting evidence shows that histone methylation, a typical epigenetic mark, is crucial for gene expression regulation during aging. Decreased trimethylation of Lys 36 on histone H3 (H3K36me3) in worms and yeast is reported to shorten lifespan. The function of H3K36me2 in aging remains unclear. In this study, we identified Caenorhabditis elegans SET-18 as a histone H3K36 dimethyltransferase. SET-18 deletion extended lifespan and increased oxidative stress resistance, dependent on daf-16 activity in the insulin/IGF pathway. In set-18 mutants, transcription of daf-16 isoform a (daf-16a) was specifically upregulated. Accordingly, a decrease in H3K36me2 on daf-16a promoter was observed. Muscle-specific expression of SET-18 increased in aged worms (day 7 and day 11), attributable to elevation of global H3K36me2 and inhibition of daf-16a expression. Consequently, longevity was shortened. These findings suggested that chromatic repression mediated by tissue-specific H3K36 dimethyltransferase might be detrimental to lifespan and may have implications in human age-related diseases. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

Changes in Regenerative Capacity through Lifespan

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Maximina H. Yun

2015-10-01

Full Text Available Most organisms experience changes in regenerative abilities through their lifespan. During aging, numerous tissues exhibit a progressive decline in homeostasis and regeneration that results in tissue degeneration, malfunction and pathology. The mechanisms responsible for this decay are both cell intrinsic, such as cellular senescence, as well as cell-extrinsic, such as changes in the regenerative environment. Understanding how these mechanisms impact on regenerative processes is essential to devise therapeutic approaches to improve tissue regeneration and extend healthspan. This review offers an overview of how regenerative abilities change through lifespan in various organisms, the factors that underlie such changes and the avenues for therapeutic intervention. It focuses on established models of mammalian regeneration as well as on models in which regenerative abilities do not decline with age, as these can deliver valuable insights for our understanding of the interplay between regeneration and aging.

Dietary supplements containing prohibited substances: A review ...

African Journals Online (AJOL)

circumstances, especially where food intake or choice is restricted. For this reason, dietary ... health hazard to all consumers.[4,12] While ... physician experienced in the treatment of obesity and familiar with this agent, on a regular basis.

Dietary modification of metabolic pathways via nuclear hormone receptors.

Science.gov (United States)

Caiozzi, Gianella; Wong, Brian S; Ricketts, Marie-Louise

2012-10-01

Nuclear hormone receptors (NHRs), as ligand-dependent transcription factors, have emerged as important mediators in the control of whole body metabolism. Because of the promiscuous nature of several members of this superfamily that have been found to bind ligand with lower affinity than the classical steroid NHRs, they consequently display a broader ligand selectivity. This promiscuous nature has facilitated various bioactive dietary components being able to act as agonist ligands for certain members of the NHR superfamily. By binding to these NHRs, bioactive dietary components are able to mediate changes in various metabolic pathways, including, glucose, cholesterol and triglyceride homeostasis among others. This review will provide a general overview of the nuclear hormone receptors that have been shown to be activated by dietary components. The physiological consequences of such receptor activation by these dietary components will then be discussed in more detail. Copyright © 2012 John Wiley & Sons, Ltd.

Dietary restraint in college women: fear of an imperfect fat self is stronger than hope of a perfect thin self.

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Dalley, Simon E; Toffanin, Paolo; Pollet, Thomas V

2012-09-01

We predicted that the perceived likelihood of acquiring a hoped-for thin self would mediate perfectionistic strivings on dietary restraint, and that the perceived likelihood of acquiring a feared fat self would mediate perfectionistic concerns on dietary restraint. We also predicted that the mediation pathway from perfectionistic concerns to dietary restraint would have a greater impact than that from perfectionistic strivings. Participants were 222 female college students who reported their height and weight and completed measures of perfectionism, the likelihood of acquiring the feared fat and hoped-for thin selves, and dietary restraint. Statistical analyses revealed that the perceived likelihood of acquiring the feared fat self mediated both perfectionistic concerns and perfectionistic strivings on dietary restraint, and that the mediating pathway from perfectionistic concerns to dietary restraint was greater than that from perfectionistic strivings. Implications for future research and eating pathology interventions are discussed. Copyright © 2012 Elsevier Ltd. All rights reserved.

Pomegranate juice enhances healthy lifespan in Drosophila melanogaster

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Padmavathy eVenkatasubramanian

2014-12-01

Full Text Available Exploring innovative ways to ensure healthy ageing of populations is a pre-requisite to contain rising healthcare costs. Scientific research into the principles and practices of traditional medicines can provide new insights and simple solutions to lead a healthy life. Rasayana is a dedicated branch of Ayurveda (an Indian medicine that deals with methods to increase vitality and delay aging through the use of diet, herbal supplements and other lifestyle practices. The life-span and health-span enhancing actions of the fruits of Pomegranate (Punica granatum L., a well-known Rasayana, were tested on Drosophila melanogaster (fruitfly model. Supplementation of standard corn meal with 10% (v/v pomegranate juice (PJ extended the life-span of male and female flies by 18% and 8% respectively. When male and female flies were mixed and reared together, there was 19% increase in the longevity of PJ fed flies, as assessed by MSD, the median survival day (24.8. MSD for control and resveratrol (RV groups was at 20.8 and 23.1 days respectively. A two-fold enhancement in fecundity, improved resistance to oxidative stress (H2O2 and paraquat induced and to Candida albicans infection were observed in PJ fed flies. Further, the flies in the PJ fed group were physically active over an extended period of time, as assessed by the climbing assay. PJ thus outperformed both control and RV groups in the life-span and health-span parameters tested. This study provides the scope to explore the potential of PJ as a nutraceutical to improve health span and lifespan in humans.

Gengnianchun Extends the Lifespan of Caenorhabditis elegans via the Insulin/IGF-1 Signalling Pathway

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Fanhui Meng

2018-01-01

Full Text Available Gengnianchun (GNC, a traditional Chinese medicine (TCM, is believed to have beneficial effects on ageing-related diseases, such as antioxidant properties and effects against Aβ-induced toxicity. We previously found that GNC extended the lifespan of Caenorhabditis elegans. However, the mechanism underlying this effect was unclear. In this study, we further explored the mechanisms of GNC using a C. elegans model. GNC significantly increased the lifespan of C. elegans and enhanced oxidative and thermal stress resistance. Moreover, chemotaxis increased after GNC treatment. RNA-seq analysis showed that GNC regulated genes associated with longevity. We also conducted lifespan assays with a series of worm mutants. The results showed that GNC significantly extended the lifespan of several mutant strains, including eat-2 (ad465, rsks-1 (ok1255, and glp-1 (e2144, suggesting that the prolongevity effect of GNC is independent of the function of these genes. However, GNC failed to extend the lifespan of daf-2 (e1370, age-1 (hx546, and daf-16 (mu86 mutant strains. Our findings suggest that GNC extends the lifespan of C. elegans via the insulin/IGF-1 signalling pathway and may be a potential antiageing agent.

Nicotinamide Improves Aspects of Healthspan, but Not Lifespan, in Mice.

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Mitchell, Sarah J; Bernier, Michel; Aon, Miguel A; Cortassa, Sonia; Kim, Eun Young; Fang, Evandro F; Palacios, Hector H; Ali, Ahmed; Navas-Enamorado, Ignacio; Di Francesco, Andrea; Kaiser, Tamzin A; Waltz, Tyler B; Zhang, Ning; Ellis, James L; Elliott, Peter J; Frederick, David W; Bohr, Vilhelm A; Schmidt, Mark S; Brenner, Charles; Sinclair, David A; Sauve, Anthony A; Baur, Joseph A; de Cabo, Rafael

2018-03-06

The role in longevity and healthspan of nicotinamide (NAM), the physiological precursor of NAD + , is elusive. Here, we report that chronic NAM supplementation improves healthspan measures in mice without extending lifespan. Untargeted metabolite profiling of the liver and metabolic flux analysis of liver-derived cells revealed NAM-mediated improvement in glucose homeostasis in mice on a high-fat diet (HFD) that was associated with reduced hepatic steatosis and inflammation concomitant with increased glycogen deposition and flux through the pentose phosphate and glycolytic pathways. Targeted NAD metabolome analysis in liver revealed depressed expression of NAM salvage in NAM-treated mice, an effect counteracted by higher expression of de novo NAD biosynthetic enzymes. Although neither hepatic NAD + nor NADP + was boosted by NAM, acetylation of some SIRT1 targets was enhanced by NAM supplementation in a diet- and NAM dose-dependent manner. Collectively, our results show health improvement in NAM-supplemented HFD-fed mice in the absence of survival effects. Published by Elsevier Inc.

Emotional Egocentricity Bias across the life-span

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Federica eRiva

2016-04-01

Full Text Available In our daily lives, we often have to quickly estimate the emotions of our conspecifics in order to have successful social interactions. While this estimation process seems quite easy when we are ourselves in a neutral or equivalent emotional state, it has recently been shown that in case of incongruent emotional states between ourselves and the others, our judgments can be biased. This phenomenon, introduced to the literature with the term Emotional Egocentricity Bias (EEB, has been found to occur in young adults and, to a greater extent, in children. However, how EEB changes across the life-span from adolescence to old age has been largely unexplored. In this study, we recruited 114 female participants subdivided in four cohorts (adolescents, young adults, middle-aged adults, older adults to examine EEB age-related changes. Participants were administered with a paradigm which, by making use of visuo-tactile stimulation that elicits conflicting feelings in paired participants, allows the valid and reliable exploration of EEB. Results highlighted a U-shaped relation between age and EEB, revealing higher emotional egocentricity in adolescents and older adults compared to young and middle-aged adults. These results are in line with the neuroscientific literature which has recently shown that overcoming EEB is associated with a greater activation of a portion of the parietal lobe, namely the right Supramarginal Gyrus (rSMG. This is an area that reaches full maturation only by the end of adolescence, and displays an early decay in older age. Thus, the age-related changes of the EEB could be possibly due to the life-span development of the rSMG. This study is the first one to show the quadratic relation between age and the EEB and set a milestone for further research exploring the neural correlates of the life-span development of the EEB. Future studies are needed in order to generalize these results to the male population and to explore gender

Conditional abrogation of Atm in osteoclasts extends osteoclast lifespan and results in reduced bone mass.

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Hirozane, Toru; Tohmonda, Takahide; Yoda, Masaki; Shimoda, Masayuki; Kanai, Yae; Matsumoto, Morio; Morioka, Hideo; Nakamura, Masaya; Horiuchi, Keisuke

2016-09-28

Ataxia-telangiectasia mutated (ATM) kinase is a central component involved in the signal transduction of the DNA damage response (DDR) and thus plays a critical role in the maintenance of genomic integrity. Although the primary functions of ATM are associated with the DDR, emerging data suggest that ATM has many additional roles that are not directly related to the DDR, including the regulation of oxidative stress signaling, insulin sensitivity, mitochondrial homeostasis, and lymphocyte development. Patients and mice lacking ATM exhibit growth retardation and lower bone mass; however, the mechanisms underlying the skeletal defects are not fully understood. In the present study, we generated mutant mice in which ATM is specifically inactivated in osteoclasts. The mutant mice did not exhibit apparent developmental defects but showed reduced bone mass due to increased osteoclastic bone resorption. Osteoclasts lacking ATM were more resistant to apoptosis and showed a prolonged lifespan compared to the controls. Notably, the inactivation of ATM in osteoclasts resulted in enhanced NF-κB signaling and an increase in the expression of NF-κB-targeted genes. The present study reveals a novel function for ATM in regulating bone metabolism by suppressing the lifespan of osteoclasts and osteoclast-mediated bone resorption.

Parahippocampal Cortex Mediates the Relationship between Lutein and Crystallized Intelligence in Healthy, Older Adults.

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Zamroziewicz, Marta K; Paul, Erick J; Zwilling, Chris E; Johnson, Elizabeth J; Kuchan, Matthew J; Cohen, Neal J; Barbey, Aron K

2016-01-01

Introduction: Although, diet has a substantial influence on the aging brain, the relationship between dietary nutrients and aspects of brain health remains unclear. This study examines the neural mechanisms that mediate the relationship between a carotenoid important for brain health across the lifespan, lutein, and crystallized intelligence in cognitively intact older adults. We hypothesized that higher serum levels of lutein are associated with better performance on a task of crystallized intelligence, and that this relationship is mediated by gray matter structure of regions within the temporal cortex. This investigation aims to contribute to a growing line of evidence, which suggests that particular nutrients may slow or prevent aspects of cognitive decline by targeting specific features of brain aging. Methods: We examined 76 cognitively intact adults between the ages of 65 and 75 to investigate the relationship between serum lutein, tests of crystallized intelligence (measured by the Wechsler Abbreviated Scale of Intelligence), and gray matter volume of regions within the temporal cortex. A three-step mediation analysis was implemented using multivariate linear regressions to control for age, sex, education, income, depression status, and body mass index. Results: The mediation analysis revealed that gray matter thickness of one region within the temporal cortex, the right parahippocampal cortex (Brodmann's Area 34), partially mediates the relationship between serum lutein and crystallized intelligence. Conclusion: These results suggest that the parahippocampal cortex acts as a mediator of the relationship between serum lutein and crystallized intelligence in cognitively intact older adults. Prior findings substantiate the individual relationships reported within the mediation, specifically the links between (i) serum lutein and temporal cortex structure, (ii) serum lutein and crystallized intelligence, and (iii) parahippocampal cortex structure and

Aging, adiposity, and calorie restriction.

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Fontana, Luigi; Klein, Samuel

2007-03-07

Excessive calorie intake and subsequent obesity increases the risk of developing chronic disease and decreases life expectancy. In rodent models, calorie restriction with adequate nutrient intake decreases the risk of developing chronic disease and extends maximum life span. To evaluate the physiological and clinical implications of calorie restriction with adequate nutrient intake. Search of PubMed (1966-December 2006) using terms encompassing various aspects of calorie restriction, dietary restriction, aging, longevity, life span, adiposity, and obesity; hand search of journals that focus on obesity, geriatrics, or aging; and search of reference lists of pertinent research and review articles and books. Reviewed reports (both basic science and clinical) included epidemiologic studies, case-control studies, and randomized controlled trials, with quality of data assessed by taking into account publication in a peer-reviewed journal, number of animals or individuals studied, objectivity of measurements, and techniques used to minimize bias. It is not known whether calorie restriction extends maximum life span or life expectancy in lean humans. However, calorie restriction in adult men and women causes many of the same metabolic adaptations that occur in calorie-restricted rodents and monkeys, including decreased metabolic, hormonal, and inflammatory risk factors for diabetes, cardiovascular disease, and possibly cancer. Excessive calorie restriction causes malnutrition and has adverse clinical effects. Calorie restriction in adult men and women causes beneficial metabolic, hormonal, and functional changes, but the precise amount of calorie intake or body fat mass associated with optimal health and maximum longevity in humans is not known. In addition, it is possible that even moderate calorie restriction may be harmful in specific patient populations, such as lean persons who have minimal amounts of body fat.

Curcumin-supplemented diets increase superoxide dismutase activity and mean lifespan in Drosophila

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Curcumin is an antioxidant extracted from the root of the turmeric plant. We examined the antioxidant effect and lifespan extension of curcumin in Drosophila. To ascertain the antioxidant effects of curcumin with regard to lifespan extension and the response to reactive oxygen species, female and ma...

Avoidant restrictive food intake disorder: an illustrative case example.

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Bryant-Waugh, Rachel

2013-07-01

Avoidant/restrictive food intake disorder (ARFID) is a new diagnostic category in DSM-5. Although replacing Feeding Disorder of Infancy or Early Childhood, it is not restricted to childhood presentations. In keeping with the broader aim of revising and updating criteria and text to better reflect lifespan issues and clinical expression across the age range, ARFID is a diagnosis relevant to children, adolescents, and adults. This case example of a 13-year old boy with ARFID illustrates key issues in diagnosis and treatment planning. The issues discussed are not exhaustive, but serve as a guide for central diagnostic and treatment issues to be considered by the clinician. It is anticipated that the inclusion of specific criteria for ARFID as a category within Feeding and Eating Disorders in DSM-5 will stimulate research into its typology, prevalence, and incidence in different populations and facilitate the development of effective, evidence-based interventions for this patient group. Copyright © 2013 Wiley Periodicals, Inc.

Comparing the Developmental Genetics of Cognition and Personality over the Lifespan

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Briley, Daniel A.; Tucker-Drob, Elliot M.

2015-01-01

Objective Empirical studies of cognitive ability and personality have tended to operate in isolation of one another. We suggest that returning to a unified approach to considering the development of individual differences in both cognition and personality can enrich our understanding of human development. Method We draw on previous meta-analyses of longitudinal, behavior genetic studies of cognition and personality across the lifespan, focusing particular attention on age trends in heritability and differential stability. Results Both cognition and personality are moderately heritable and exhibit large increases in stability with age; however, marked differences are evident. First, the heritability of cognition increases substantially with child age, while the heritability of personality decreases modestly with age. Second, increasing stability of cognition with age is overwhelmingly mediated by genetic factors, whereas increasing stability of personality with age is entirely mediated by environmental factors. Third, the maturational time-course of stability differs: Stability of cognition nears its asymptote by the end of the first decade of life, whereas stability of personality takes three decades to near its asymptote. Conclusions We discuss how proximal gene-environment dynamics, developmental processes, broad social contexts, and evolutionary pressures may intersect to give rise to these divergent patterns. PMID:26045299

Aging, neurogenesis, and caloric restriction in different model organisms.

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Arslan-Ergul, Ayca; Ozdemir, A Tugrul; Adams, Michelle M

2013-08-01

Brain aging is a multifactorial process that is occurring across multiple cognitive domains. A significant complaint that occurs in the elderly is a decrement in learning and memory ability. Both rodents and zebrafish exhibit a similar problem with memory during aging. The neurobiological changes that underlie this cognitive decline are complex and undoubtedly influenced by many factors. Alterations in the birth of new neurons and neuron turnover may contribute to age-related cognitive problems. Caloric restriction is the only non-genetic intervention that reliably increases life span and healthspan across multiple organisms although the molecular mechanisms are not well-understood. Recently the zebrafish has become a popular model organism for understanding the neurobiological consequences but to date very little work has been performed. Similarly, few studies have examined the effects of dietary restriction in zebrafish. Here we review the literature related to memory decline, neurogenesis, and caloric restriction across model organisms and suggest that zebrafish has the potential to be an important animal model for understanding the complex interactions between age, neurobiological changes in the brain, and dietary regimens or their mimetics as interventions.

Workplace flexibility across the lifespan

OpenAIRE

Bal, Pieter; Jansen, Paul G W

2016-01-01

As demographic changes impact the workplace, governments, organizations and workers arelooking for ways to sustain optimal working lives at higher ages. Workplace flexibility has beenintroduced as a potential way workers can have more satisfying working lives until theirretirement ages. This paper presents a critical review of the literature on workplace flexibilityacross the lifespan. It discusses how flexibility has been conceptualized across differentdisciplines, and postulates a definitio...

Dietary phosphorus acutely impairs endothelial function.

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Shuto, Emi; Taketani, Yutaka; Tanaka, Rieko; Harada, Nagakatsu; Isshiki, Masashi; Sato, Minako; Nashiki, Kunitaka; Amo, Kikuko; Yamamoto, Hironori; Higashi, Yukihito; Nakaya, Yutaka; Takeda, Eiji

2009-07-01

Excessive dietary phosphorus may increase cardiovascular risk in healthy individuals as well as in patients with chronic kidney disease, but the mechanisms underlying this risk are not completely understood. To determine whether postprandial hyperphosphatemia may promote endothelial dysfunction, we investigated the acute effect of phosphorus loading on endothelial function in vitro and in vivo. Exposing bovine aortic endothelial cells to a phosphorus load increased production of reactive oxygen species, which depended on phosphorus influx via sodium-dependent phosphate transporters, and decreased nitric oxide production via inhibitory phosphorylation of endothelial nitric oxide synthase. Phosphorus loading inhibited endothelium-dependent vasodilation of rat aortic rings. In 11 healthy men, we alternately served meals containing 400 mg or 1200 mg of phosphorus in a double-blind crossover study and measured flow-mediated dilation of the brachial artery before and 2 h after the meals. The high dietary phosphorus load increased serum phosphorus at 2 h and significantly decreased flow-mediated dilation. Flow-mediated dilation correlated inversely with serum phosphorus. Taken together, these findings suggest that endothelial dysfunction mediated by acute postprandial hyperphosphatemia may contribute to the relationship between serum phosphorus level and the risk for cardiovascular morbidity and mortality.

A Modified Carbon Monoxide Breath Test for Measuring Erythrocyte Lifespan in Small Animals

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Yong-Jian Ma

2016-01-01

Full Text Available This study was to develop a CO breath test for RBC lifespan estimation of small animals. The ribavirin induced hemolysis rabbit models were placed individually in a closed rebreath cage and air samples were collected for measurement of CO concentration. RBC lifespan was calculated from accumulated CO, blood volume, and hemoglobin concentration data. RBC lifespan was determined in the same animals with the standard biotin-labeling method. RBC lifespan data obtained by the CO breath test method for control (CON, 49.0±5.9 d rabbits, rabbits given 10 mg/kg·d−1 of ribavirin (RIB10, 31.0±4.0 d, and rabbits given 20 mg/kg·d−1 of ribavirin (RIB20, 25.0±2.9 d were statistically similar (all p>0.05 to and linearly correlated (r=0.96, p<0.01 with the RBC lifespan data obtained for the same rabbits by the standard biotin-labeling method (CON, 51.0±2.7 d; RIB10, 33.0±1.3 d; and RIB20, 27.0±0.8 d. The CO breath test method takes less than 3 h to complete, whereas the standard method requires at least several weeks. In conclusion, the CO breath test method provides a simple and rapid means of estimating RBC lifespan and is feasible for use with small animal models.

Dietary Advanced Glycation End Products and Cardiometabolic Risk.

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Luévano-Contreras, Claudia; Gómez-Ojeda, Armando; Macías-Cervantes, Maciste Habacuc; Garay-Sevilla, Ma Eugenia

2017-08-01

This report analyzes emerging evidence about the role of dietary advanced glycation end products (AGEs) as a cardiometabolic risk factor. Two important aspects are discussed: First, the modulation of AGE load by dietary AGEs; second, if the evidence of clinical and observational studies is enough to make dietary recommendations towards lowering AGE intake. Clinical studies in subjects with diabetes mellitus have shown that high intake of dietary AGEs increases inflammation markers, oxidative stress, and could impair endothelial function. In subjects at risk for cardiometabolic diseases (with overweight, obesity, or prediabetes), dietary AGE restriction decreases some inflammatory molecules and improves insulin sensitivity. However, studies in healthy subjects are limited, and not all of the studies have shown a decrease in circulating AGEs. Therefore, it is still unclear if dietary AGEs represent a health concern for people potentially at risk for cardiometabolic diseases. The evidence shows that dietary AGEs are bioavailable and absorbed, and the rate of excretion depends on dietary intake. The metabolic fate of most dietary AGEs remains unknown. Regardless, most studies have shown that by diminishing AGE intake, circulating levels will also decrease. Thus, dietary AGEs can modulate the AGE load at least in patients with DM, overweight, or obesity. Studies with specific clinical outcomes and large-scale observational studies are needed for a better risk assessment of dietary AGEs and to establish dietary recommendations accordingly.

Carbon dioxide sensing modulates lifespan and physiology in Drosophila.

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Poon, Peter C; Kuo, Tsung-Han; Linford, Nancy J; Roman, Gregg; Pletcher, Scott D

2010-04-20

For nearly all life forms, perceptual systems provide access to a host of environmental cues, including the availability of food and mates as well as the presence of disease and predators. Presumably, individuals use this information to assess the current and future states of the environment and to enact appropriate developmental, behavioral, and regulatory decisions. Recent work using the nematode worm, Caenorhabditis elegans, and the fruit fly, Drosophila melanogaster, has established that aging is subject to modulation through neurosensory systems and that this regulation is evolutionarily conserved. To date, sensory manipulations shown to impact Drosophila aging have involved general loss of function or manipulation of complex stimuli. We therefore know little about the specific inputs, sensors, or associated neural circuits that affect these life and death decisions. We find that a specialized population of olfactory neurons that express receptor Gr63a (a component of the olfactory receptor for gaseous phase CO(2)) affects fly lifespan and physiology. Gr63a loss of function leads to extended lifespan, increased fat deposition, and enhanced resistance to some (but not all) environmental stresses. Furthermore, we find that the reduced lifespan that accompanies exposure to odors from live yeast is dependent on Gr63a. Together these data implicate a specific sensory cue (CO(2)) and its associated receptor as having the ability to modulate fly lifespan and alter organism stress response and physiology. Because Gr63a is expressed in a well-defined population of neurons, future work may now be directed at dissecting more complex neurosensory and neuroendocrine circuits that modulate aging in Drosophila.

Dietary fat content alters insulin-mediated glucose metabolism in healthy men

NARCIS (Netherlands)

Bisschop, PH; de Metz, J; Ackermans, MT; Endert, E; Pijl, H; Kuipers, F; Meijer, AJ; Sauerwein, HP; Romijn, JA

Background: A high dietary fat intake is involved in the pathogenesis of insulin resistance. Objective: The aim was to compare the effect of different amounts of dietary fat on hepatic and peripheral insulin sensitivity. Design: Six healthy men were studied on 3 occasions after consuming for 11 d

Vitamin D-deficient osteomalacia due to excessive self-restrictions for atopic dermatitis.

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Shikino, Kiyoshi; Ikusaka, Masatomi; Yamashita, Tomoko

2014-07-04

A 34-year-old Japanese woman presented with a 2-year history of generalised bone pain, muscle weakness and gait disturbance. The patient had been following a restricted diet (without fish or dairy products) and avoiding ultraviolet exposure for 8 years to manage her worsening atopic dermatitis. Physical examination revealed generalised bone tenderness and bilateral symmetric proximal muscle weakness. Vitamin D-deficient osteomalacia was diagnosed based on the laboratory examination findings, which indicated high serum alkaline phosphatase, high intact parathyroid hormone, and low 25-hydroxyvitamin D levels. Her symptoms improved after oral active vitamin D and calcium administration. To the best our knowledge, this case is the first report of vitamin D-deficient osteomalacia in an adult patient due to excessive dietary restriction for managing atopic dermatitis. We emphasise the importance of increasing awareness of vitamin D deficiency as a risk factor for the development of osteomalacia, and caution against excessive avoidance of sun exposure and dietary restriction. 2014 BMJ Publishing Group Ltd.

Neuromodulation and developmental contextual influences on neural and cognitive plasticity across the lifespan.

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Li, Shu-Chen

2013-11-01

Behavioral, cognitive, and motivational development entails co-constructive interactions between the environmental and social influences from the developmental context, on the one hand, and the individual's neurobiological inheritance, on the other hand. Key brain networks underlying cognition, emotion, and motivation are innervated by major transmitter systems (e.g., the catecholamines and acetylcholine). Thus, the maturation and senescence of neurotransmitter systems have direct implications for lifespan development. In addition to reviewing evidence on life age differences in dopaminergic modulation and cognitive development, this brief review selectively highlights recent findings on how important influences from the developmental context, such as reward-mediated motivational processes, transgenerational stress transmission, psychosocial stress, and cognitive interventions, may, in part, exert their effects on brain and behavioral development through their effects on neuromodulatory mechanisms. Copyright © 2013 Elsevier Ltd. All rights reserved.

In vitro cellular adaptations of indicators of longevity in response to treatment with serum collected from humans on calorie restricted diets.

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Joanne S Allard

2008-09-01

Full Text Available Calorie restriction (CR produces several health benefits and increases lifespan in many species. Studies suggest that alternate-day fasting (ADF and exercise can also provide these benefits. Whether CR results in lifespan extension in humans is not known and a direct investigation is not feasible. However, phenotypes observed in CR animals when compared to ad libitum fed (AL animals, including increased stress resistance and changes in protein expression, can be simulated in cells cultured with media supplemented with blood serum from CR and AL animals. Two pilot studies were undertaken to examine the effects of ADF and CR on indicators of health and longevity in humans. In this study, we used sera collected from those studies to culture human hepatoma cells and assessed the effects on growth, stress resistance and gene expression. Cells cultured in serum collected at the end of the dieting period were compared to cells cultured in serum collected at baseline (before the dieting period. Cells cultured in serum from ADF participants, showed a 20% increase in Sirt1 protein which correlated with reduced triglyceride levels. ADF serum also induced a 9% decrease in proliferation and a 25% increase in heat resistance. Cells cultured in serum from CR participants induced an increase in Sirt1 protein levels by 17% and a 30% increase in PGC-1alpha mRNA levels. This first in vitro study utilizing human serum to examine effects on markers of health and longevity in cultured cells resulted in increased stress resistance and an up-regulation of genes proposed to be indicators of increased longevity. The use of this in vitro technique may be helpful for predicting the potential of CR, ADF and other dietary manipulations to affect markers of longevity in humans.

Generation of herpesvirus entry mediator (HVEM)-restricted herpes simplex virus type 1 mutant viruses: resistance of HVEM-expressing cells and identification of mutations that rescue nectin-1 recognition.

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Uchida, Hiroaki; Shah, Waris A; Ozuer, Ali; Frampton, Arthur R; Goins, William F; Grandi, Paola; Cohen, Justus B; Glorioso, Joseph C

2009-04-01

Both initial infection and cell-to-cell spread by herpes simplex virus type 1 (HSV-1) require the interaction of the viral glycoprotein D (gD) with an entry receptor on the cell surface. The two major HSV entry receptors, herpesvirus entry mediator (HVEM) and nectin-1, mediate infection independently but are coexpressed on a variety of cells. To determine if both receptors are active in these instances, we have established mutant viruses that are selectively impaired for recognition of one or the other receptor. In plaque assays, these viruses showed approximately 1,000-fold selectivity for the matched receptor over the mismatched receptor. Separate assays showed that each virus is impaired for both infection and spread through the mismatched receptor. We tested several human tumor cell lines for susceptibility to these viruses and observed that HT29 colon carcinoma cells are susceptible to infection by nectin-1-restricted virus but are highly resistant to HVEM-restricted virus infection, despite readily detectable HVEM expression on the cell surface. HVEM cDNA isolated from HT29 cells rendered HSV-resistant cells permissive for infection by the HVEM-restricted virus, suggesting that HT29 cells lack a cofactor for HVEM-mediated infection or express an HVEM-specific inhibitory factor. Passaging of HVEM-restricted virus on nectin-1-expressing cells yielded a set of gD missense mutations that each restored functional recognition of nectin-1. These mutations identify residues that likely play a role in shaping the nectin-1 binding site of gD. Our findings illustrate the utility of these receptor-restricted viruses in studying the early events in HSV infection.

Building lifespan: effect on the environmental impact of building components in a Danish perspective

DEFF Research Database (Denmark)

Marsh, Rob

2017-01-01

of building lifespan are inadequately addressed. The aim of this research is therefore to explore how environmental impact from building components is affected by building lifespans of 50, 80, 100 and 120 years in a Danish context. LCAs are undertaken for 792 parametric variations of typical construction...... solutions, covering all primary building components and based on contemporary practice. A full statistical analysis is carried out, which shows a significant statistical correlation between changes in building lifespan and environmental impact for all primary building components, except windows......Construction professionals must now integrate environmental concerns with life cycle assessment (LCA) early in the procurement process. Building lifespan is important to LCA, since results must be normalized on an annualized basis for comparison. However, the scientific literature shows that issues...

Piceatannol extends the lifespan of Caenorhabditis elegans via DAF-16.

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Shen, Peiyi; Yue, Yiren; Sun, Quancai; Kasireddy, Nandita; Kim, Kee-Hong; Park, Yeonhwa

2017-05-06

Piceatannol is a natural stilbene with many beneficial effects, such as antioxidative, anti-inflammatory, antiatherogenic activities; however, its role on aging is not known. In this study, we used Caenorhabditis elegans as an animal model to study the effect of piceatannol on its lifespan and investigated the underlying mechanisms. The results showed that 50 and 100 µM piceatannol significantly extended the lifespan of C. elegans without altering the growth rate, worm size and progeny production. Piceatannol delayed the age-related decline of pumping rate and locomotive activity, and protected the worms from heat and oxidative stress. This study further indicated that lifespan extension and enhanced stress resistance induced by piceatannol requires DAF-16. Since DAF-16 is conserved from nematodes to mammals, our study may have important implications in utilizing piceatannol to promote healthy aging and combat age-related disease in humans. © 2016 BioFactors, 43(3):379-387, 2017. © 2017 International Union of Biochemistry and Molecular Biology.

Mechanisms of increased lifespan in hypoxia in the alfalfa leafcutting bee, Megachile rotundata

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Genetic variation accounts for a small amount of variation in lifespan, while environmental stressors are strong predictors. Hypoxia is an environmental stress that increases longevity in some contexts, but the mechanisms remain poorly understood. In the bee Megachile rotundata, lifespan doubles upo...

Nmdmc overexpression extends Drosophila lifespan and reduces levels of mitochondrial reactive oxygen species

Energy Technology Data Exchange (ETDEWEB)

Yu, Suyeun [Department of Preventive Medicine, College of Medicine, Korea University, 73 Inchon-ro, Seongbuk-gu, Seoul 136-705 (Korea, Republic of); Jang, Yeogil; Paik, Donggi [Department of Physiology, College of Medicine, Korea University, 73 Inchon-ro, Seongbuk-gu, Seoul 136-705 (Korea, Republic of); Lee, Eunil, E-mail: eunil@korea.ac.kr [Department of Preventive Medicine, College of Medicine, Korea University, 73 Inchon-ro, Seongbuk-gu, Seoul 136-705 (Korea, Republic of); Park, Joong-Jean, E-mail: parkjj@korea.ac.kr [Department of Physiology, College of Medicine, Korea University, 73 Inchon-ro, Seongbuk-gu, Seoul 136-705 (Korea, Republic of)

2015-10-02

NAD-dependent methylenetetrahydrofolate dehydrogenase-methenyltetrahydrofolate cyclohydrolase (NMDMC) is a bifunctional enzyme involved in folate-dependent metabolism and highly expressed in rapidly proliferating cells. However, Nmdmc physiological roles remain unveiled. We found that ubiquitous Nmdmc overexpression enhanced Drosophila lifespan and stress resistance. Interestingly, Nmdmc overexpression in the fat body was sufficient to increase lifespan and tolerance against oxidative stress. In addition, these conditions coincided with significant decreases in the levels of mitochondrial ROS and Hsp22 as well as with a significant increase in the copy number of mitochondrial DNA. These results suggest that Nmdmc overexpression should be beneficial for mitochondrial homeostasis and increasing lifespan. - Highlights: • Ubiquitous Nmdmc overexpression enhanced lifespan and stress tolerance. • Nmdmc overexpression in the fat body extended longevity. • Fat body-specific Nmdmc overexpression increased oxidative stress resistance. • Nmdmc overexpression decreased Hsp22 transcript levels and ROS. • Nmdmc overexpression increased mitochondrial DNA copy number.

Nmdmc overexpression extends Drosophila lifespan and reduces levels of mitochondrial reactive oxygen species

International Nuclear Information System (INIS)

Yu, Suyeun; Jang, Yeogil; Paik, Donggi; Lee, Eunil; Park, Joong-Jean

2015-01-01

NAD-dependent methylenetetrahydrofolate dehydrogenase-methenyltetrahydrofolate cyclohydrolase (NMDMC) is a bifunctional enzyme involved in folate-dependent metabolism and highly expressed in rapidly proliferating cells. However, Nmdmc physiological roles remain unveiled. We found that ubiquitous Nmdmc overexpression enhanced Drosophila lifespan and stress resistance. Interestingly, Nmdmc overexpression in the fat body was sufficient to increase lifespan and tolerance against oxidative stress. In addition, these conditions coincided with significant decreases in the levels of mitochondrial ROS and Hsp22 as well as with a significant increase in the copy number of mitochondrial DNA. These results suggest that Nmdmc overexpression should be beneficial for mitochondrial homeostasis and increasing lifespan. - Highlights: • Ubiquitous Nmdmc overexpression enhanced lifespan and stress tolerance. • Nmdmc overexpression in the fat body extended longevity. • Fat body-specific Nmdmc overexpression increased oxidative stress resistance. • Nmdmc overexpression decreased Hsp22 transcript levels and ROS. • Nmdmc overexpression increased mitochondrial DNA copy number.

Protein-restricted diets plus keto/amino acids--a valid therapeutic approach for chronic kidney disease patients.

Science.gov (United States)

Aparicio, Michel; Bellizzi, Vincenzo; Chauveau, Philippe; Cupisti, Adamasco; Ecder, Tevfik; Fouque, Denis; Garneata, Liliana; Lin, Shanyan; Mitch, William E; Teplan, Vladimír; Zakar, Gábor; Yu, Xueqing

2012-03-01

Chronic kidney disease (CKD) is increasingly common, and there is an increasing awareness that every strategy should be used to avoid complications of CKD. Restriction of dietary protein intake has been a relevant part of the management of CKD for more than 100 years, but even today, the principal goal of protein-restricted regimens is to decrease the accumulation of nitrogen waste products, hydrogen ions, phosphates, and inorganic ions while maintaining an adequate nutritional status to avoid secondary problems such as metabolic acidosis, bone disease, and insulin resistance, as well as proteinuria and deterioration of renal function. This supplement focuses on recent experimental and clinical findings related to an optimized dietary management of predialysis, dialysis, and transplanted patients as an important aspect of patient care. Nutritional treatment strategies are linked toward ameliorating metabolic and endocrine disturbances, improving/maintaining nutritional status, as well as delaying the renal replacement initiation and improving outcomes in CKD patients. A final consensus states that dietary manipulations should be considered as one of the main approaches in the management program of CKD patients and that a reasonable number of patients with moderate or severe CKD benefit from dietary protein/phosphorus restriction. Copyright © 2012 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Regional and longitudinal estimation of product lifespan distribution: a case study for automobiles and a simplified estimation method.

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Oguchi, Masahiro; Fuse, Masaaki

2015-02-03

Product lifespan estimates are important information for understanding progress toward sustainable consumption and estimating the stocks and end-of-life flows of products. Publications reported actual lifespan of products; however, quantitative data are still limited for many countries and years. This study presents regional and longitudinal estimation of lifespan distribution of consumer durables, taking passenger cars as an example, and proposes a simplified method for estimating product lifespan distribution. We estimated lifespan distribution parameters for 17 countries based on the age profile of in-use cars. Sensitivity analysis demonstrated that the shape parameter of the lifespan distribution can be replaced by a constant value for all the countries and years. This enabled a simplified estimation that does not require detailed data on the age profile. Applying the simplified method, we estimated the trend in average lifespans of passenger cars from 2000 to 2009 for 20 countries. Average lifespan differed greatly between countries (9-23 years) and was increasing in many countries. This suggests consumer behavior differs greatly among countries and has changed over time, even in developed countries. The results suggest that inappropriate assumptions of average lifespan may cause significant inaccuracy in estimating the stocks and end-of-life flows of products.

Antigenotoxicity of Dietary Coconut Oil

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Clara Lim-Sylianco

1992-06-01

Full Text Available Benzo(apyrene, dimethylnitrosamine, methylmethanesulfonate and tetracycline induced formation of micronucleated polychromatic erythrocytes indicating that these substances are genotoxic to bone marrow cells of the experimental mice.Genotoxicity of these substances to germ cells was also observed when low fertility index and high percentage dead implants were induced in experimental mice.When each genotoxin was administered to mice fed with diets containing 18 % coconut oil for 23 days, the formation of micronucleated polychromatic erythrocytes was greatly reduced. Antigenotoxic activity of dietary coconut oil was very much greater than dietary soybean oil.Germ cell genotoxicity of each genotoxin was also reduced when male mice fed the 18 % coconut oil diet were used. When male mice treated with the genotoxin was mated with virgin females, fertility index was increased in the group fed with coconut oil diet. Percentage dead implants was reduced. The antigenotoxic activity of dietary coconut oil on germ cells far exceeds that of dietary soybean oil.Dietary restriction of coconut oil diets enhanced the antigenotoxic activity of coconut oil in bone marrow cells and germs cells.Among the triacylglycerols of coconut oil, trilaurin gave the best antigenotoxic activity in bone marrow cells. Trilaurin is the major triacylglycerol in coconut oil.

Dynamic range of Nef-mediated evasion of HLA class II-restricted immune responses in early HIV-1 infection.

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Mahiti, Macdonald; Brumme, Zabrina L; Jessen, Heiko; Brockman, Mark A; Ueno, Takamasa

2015-07-31

HLA class II-restricted CD4(+) T lymphocytes play an important role in controlling HIV-1 replication, especially in the acute/early infection stage. But, HIV-1 Nef counteracts this immune response by down-regulating HLA-DR and up-regulating the invariant chain associated with immature HLA-II (Ii). Although functional heterogeneity of various Nef activities, including down-regulation of HLA class I (HLA-I), is well documented, our understanding of Nef-mediated evasion of HLA-II-restricted immune responses during acute/early infection remains limited. Here, we examined the ability of Nef clones from 47 subjects with acute/early progressive infection and 46 subjects with chronic progressive infection to up-regulate Ii and down-regulate HLA-DR and HLA-I from the surface of HIV-infected cells. HLA-I down-regulation function was preserved among acute/early Nef clones, whereas both HLA-DR down-regulation and Ii up-regulation functions displayed relatively broad dynamic ranges. Nef's ability to down-regulate HLA-DR and up-regulate Ii correlated positively at this stage, suggesting they are functionally linked in vivo. Acute/early Nef clones also exhibited higher HLA-DR down-regulation and lower Ii up-regulation functions compared to chronic Nef clones. Taken together, our results support enhanced Nef-mediated HLA class II immune evasion activities in acute/early compared to chronic infection, highlighting the potential importance of these functions following transmission. Copyright © 2015 Elsevier Inc. All rights reserved.

Myc-dependent genome instability and lifespan in Drosophila.

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Christina Greer

Full Text Available The Myc family of transcription factors are key regulators of cell growth and proliferation that are dysregulated in a large number of human cancers. When overexpressed, Myc family proteins also cause genomic instability, a hallmark of both transformed and aging cells. Using an in vivo lacZ mutation reporter, we show that overexpression of Myc in Drosophila increases the frequency of large genome rearrangements associated with erroneous repair of DNA double-strand breaks (DSBs. In addition, we find that overexpression of Myc shortens adult lifespan and, conversely, that Myc haploinsufficiency reduces mutation load and extends lifespan. Our data provide the first evidence that Myc may act as a pro-aging factor, possibly through its ability to greatly increase genome instability.

Caspase-1 but Not Caspase-11 Is Required for NLRC4-Mediated Pyroptosis and Restriction of Infection by Flagellated Legionella Species in Mouse Macrophages and In Vivo.

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Cerqueira, Daiane M; Pereira, Marcelo S F; Silva, Alexandre L N; Cunha, Larissa D; Zamboni, Dario S

2015-09-01

Gram-negative bacteria from the Legionella genus are intracellular pathogens that cause a severe form of pneumonia called Legionnaires' disease. The bacteria replicate intracellularly in macrophages, and the restriction of bacterial replication by these cells is critical for host resistance. The activation of the NAIP5/NLRC4 inflammasome, which is readily triggered in response to bacterial flagellin, is essential for the restriction of bacterial replication in murine macrophages. Once activated, this inflammasome induces pore formation and pyroptosis and facilitates the restriction of bacterial replication in macrophages. Because investigations related to the NLRC4-mediated restriction of Legionella replication were performed using mice double deficient for caspase-1 and caspase-11, we assessed the participation of caspase-1 and caspase-11 in the functions of the NLRC4 inflammasome and the restriction of Legionella replication in macrophages and in vivo. By using several species of Legionella and mice singly deficient for caspase-1 or caspase-11, we demonstrated that caspase-1 but not caspase-11 was required for pore formation, pyroptosis, and restriction of Legionella replication in macrophages and in vivo. By generating F1 mice in a mixed 129 × C57BL/6 background deficient (129 × Casp-11(-/-) ) or sufficient (129 × C57BL/6) for caspase-11 expression, we found that caspase-11 was dispensable for the restriction of Legionella pneumophila replication in macrophages and in vivo. Thus, although caspase-11 participates in flagellin-independent noncanonical activation of the NLRP3 inflammasome, it is dispensable for the activities of the NLRC4 inflammasome. In contrast, functional caspase-1 is necessary and sufficient to trigger flagellin/NLRC4-mediated restriction of Legionella spp. infection in macrophages and in vivo. Copyright © 2015 by The American Association of Immunologists, Inc.

Macrophages and Adipocytes in Human Obesity Adipose Tissue Gene Expression and Insulin Sensitivity During Calorie Restriction and Weight Stabilization

DEFF Research Database (Denmark)

Capel, F.; Klimcakova, E.; Viguerie, N.

2009-01-01

OBJECTIVE-We investigated the regulation of adipose tissue gene expression during different phases of a dietary weight loss program and its relation with insulin sensitivity. RESEARCH DESIGN AND METHODS-Twenty-two obese women followed a dietary intervention program composed of an energy restriction...... expression profiling was performed using a DNA microarray in a subgroup of eight women. RT-quantitative PCR was used for determination of mRNA levels of 31 adipose tissue macrophage markers (n = 22). RESULTS-Body weight, fat mass, and C-reactive protein level decreased and glucose disposal rate increased...... during the dietary intervention program. Transcriptome profiling revealed two main patterns of variations. The first involved 464 mostly adipocyte genes involved in metabolism that were downregulated during energy restriction, upregulated during weight stabilization, and unchanged during the dietary...

Impacts of maternal dietary protein intake on fetal survival, growth, and development.

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Herring, Cassandra M; Bazer, Fuller W; Johnson, Gregory A; Wu, Guoyao

2018-03-01

Maternal nutrition during gestation, especially dietary protein intake, is a key determinant in embryonic survival, growth, and development. Low maternal dietary protein intake can cause embryonic losses, intra-uterine growth restriction, and reduced postnatal growth due to a deficiency in specific amino acids that are important for cell metabolism and function. Of note, high maternal dietary protein intake can also result in intra-uterine growth restriction and embryonic death, due to amino acid excesses, as well as the toxicity of ammonia, homocysteine, and H 2 S that are generated from amino acid catabolism. Maternal protein nutrition has a pronounced impact on fetal programming and alters the expression of genes in the fetal genome. As a precursor to the synthesis of molecules (e.g. nitric oxide, polyamines, and creatine) with cell signaling and metabolic functions, L-arginine (Arg) is essential during pregnancy for growth and development of the conceptus. With inadequate maternal dietary protein intake, Arg and other important amino acids are deficient in mother and fetus. Dietary supplementation of Arg during gestation has been effective in improving embryonic survival and development of the conceptus in many species, including humans, pigs, sheep, mice, and rats. Both the balance among amino acids and their quantity are critical for healthy pregnancies and offspring. Impact statement This review aims at: highlighting adverse effects of elevated levels of ammonia in mother or fetus on embryonic/fetal survival, growth, and development; helping nutritionists and practitioners to understand the mechanisms whereby elevated levels of ammonia in mother or fetus results in embryonic/fetal death, growth restriction, and developmental abnormalities; and bringing, into the attention of nutritionists and practitioners, the problems of excess or inadequate dietary intake of protein or amino acids on pregnancy outcomes in animals and humans. The article provides new

Lifespan and reproduction in brain-specific miR-29-knockdown mouse.

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Takeda, Toru; Tanabe, Hiroyuki

2016-03-18

The microRNA miR-29 is widely distributed and highly expressed in adult mouse brain during the mouse's lifetime. We recently created conditional mutant mice whose miR-29 was brain-specifically knocked down through overexpression of an antisense RNA transgene against miR-29. To explore a role for brain miR-29 in maximizing organismal fitness, we assessed somatic growth, reproduction, and lifespan in the miR-29-knockdown (KD) mice and their wild-type (WT) littermates. The KD mice were developmentally indistinguishable from WT mice with respect to gross morphology and physical activity. Fertility testing revealed that KD males were subfertile, whereas KD females were hyperfertile, only in terms of reproductive success, when compared to their gender-matched WT correspondents. Another phenotypic difference between KD and WT animals appeared in their lifespan data; KD males displayed an overall increasing tendency in post-reproductive survival relative to WT males. In contrast, KD females were prone to shorter lifespans than WT females. These results clarify that brain-targeted miR-29 knockdown affects both lifespan and reproduction in a gender-dependent manner, and moreover that the reciprocal responsiveness to the miR-29 knockdown between these two phenotypes in both genders closely follow life-course models based on the classical trade-off prediction wherein elaborate early-life energetic investment in reproduction entails accelerated late-life declines in survival, and vice versa. Thus, this study identified miR-29 as the first mammalian miRNA that is directly implicated in the lifetime trade-off between the two major fitness components, lifespan and reproduction. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Sex differences and stress across the lifespan

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Bale, Tracy L; Epperson, C Neill

2015-01-01

Sex differences in stress responses can be found at all stages of life and are related to both the organizational and activational effects of gonadal hormones and to genes on the sex chromosomes. As stress dysregulation is the most common feature across neuropsychiatric diseases, sex differences in how these pathways develop and mature may predict sex-specific periods of vulnerability to disruption and increased disease risk or resilience across the lifespan. The aging brain is also at risk to the effects of stress, where the rapid decline of gonadal hormones in women combined with cellular aging processes promote sex biases in stress dysregulation. In this Review, we discuss potential underlying mechanisms driving sex differences in stress responses and their relevance to disease. Although stress is involved in a much broader range of diseases than neuropsychiatric ones, we highlight here this area and its examples across the lifespan. PMID:26404716

Sex differences and stress across the lifespan.

Science.gov (United States)

Bale, Tracy L; Epperson, C Neill

2015-10-01

Sex differences in stress responses can be found at all stages of life and are related to both the organizational and activational effects of gonadal hormones and to genes on the sex chromosomes. As stress dysregulation is the most common feature across neuropsychiatric diseases, sex differences in how these pathways develop and mature may predict sex-specific periods of vulnerability to disruption and increased disease risk or resilience across the lifespan. The aging brain is also at risk to the effects of stress, where the rapid decline of gonadal hormones in women combined with cellular aging processes promote sex biases in stress dysregulation. In this Review, we discuss potential underlying mechanisms driving sex differences in stress responses and their relevance to disease. Although stress is involved in a much broader range of diseases than neuropsychiatric ones, we highlight here this area and its examples across the lifespan.

Carbon dioxide sensing modulates lifespan and physiology in Drosophila.

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Peter C Poon

Full Text Available For nearly all life forms, perceptual systems provide access to a host of environmental cues, including the availability of food and mates as well as the presence of disease and predators. Presumably, individuals use this information to assess the current and future states of the environment and to enact appropriate developmental, behavioral, and regulatory decisions. Recent work using the nematode worm, Caenorhabditis elegans, and the fruit fly, Drosophila melanogaster, has established that aging is subject to modulation through neurosensory systems and that this regulation is evolutionarily conserved. To date, sensory manipulations shown to impact Drosophila aging have involved general loss of function or manipulation of complex stimuli. We therefore know little about the specific inputs, sensors, or associated neural circuits that affect these life and death decisions. We find that a specialized population of olfactory neurons that express receptor Gr63a (a component of the olfactory receptor for gaseous phase CO(2 affects fly lifespan and physiology. Gr63a loss of function leads to extended lifespan, increased fat deposition, and enhanced resistance to some (but not all environmental stresses. Furthermore, we find that the reduced lifespan that accompanies exposure to odors from live yeast is dependent on Gr63a. Together these data implicate a specific sensory cue (CO(2 and its associated receptor as having the ability to modulate fly lifespan and alter organism stress response and physiology. Because Gr63a is expressed in a well-defined population of neurons, future work may now be directed at dissecting more complex neurosensory and neuroendocrine circuits that modulate aging in Drosophila.

Lifespan differences in hematopoietic stem cells are due to imperfect repair and unstable mean-reversion.

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Hans B Sieburg

2013-04-01

Full Text Available The life-long supply of blood cells depends on the long-term function of hematopoietic stem cells (HSCs. HSCs are functionally defined by their multi-potency and self-renewal capacity. Because of their self-renewal capacity, HSCs were thought to have indefinite lifespans. However, there is increasing evidence that genetically identical HSCs differ in lifespan and that the lifespan of a HSC is predetermined and HSC-intrinsic. Lifespan is here defined as the time a HSC gives rise to all mature blood cells. This raises the intriguing question: what controls the lifespan of HSCs within the same animal, exposed to the same environment? We present here a new model based on reliability theory to account for the diversity of lifespans of HSCs. Using clonal repopulation experiments and computational-mathematical modeling, we tested how small-scale, molecular level, failures are dissipated at the HSC population level. We found that the best fit of the experimental data is provided by a model, where the repopulation failure kinetics of each HSC are largely anti-persistent, or mean-reverting, processes. Thus, failure rates repeatedly increase during population-wide division events and are counteracted and decreased by repair processes. In the long-run, a crossover from anti-persistent to persistent behavior occurs. The cross-over is due to a slow increase in the mean failure rate of self-renewal and leads to rapid clonal extinction. This suggests that the repair capacity of HSCs is self-limiting. Furthermore, we show that the lifespan of each HSC depends on the amplitudes and frequencies of fluctuations in the failure rate kinetics. Shorter and longer lived HSCs differ significantly in their pre-programmed ability to dissipate perturbations. A likely interpretation of these findings is that the lifespan of HSCs is determined by preprogrammed differences in repair capacity.

No influence of Indy on lifespan in Drosophila after correction for genetic and cytoplasmic background effects.

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Janne M Toivonen

2007-06-01

Full Text Available To investigate whether alterations in mitochondrial metabolism affect longevity in Drosophila melanogaster, we studied lifespan in various single gene mutants, using inbred and outbred genetic backgrounds. As positive controls we included the two most intensively studied mutants of Indy, which encodes a Drosophila Krebs cycle intermediate transporter. It has been reported that flies heterozygous for these Indy mutations, which lie outside the coding region, show almost a doubling of lifespan. We report that only one of the two mutants lowers mRNA levels, implying that the lifespan extension observed is not attributable to the Indy mutations themselves. Moreover, neither Indy mutation extended lifespan in female flies in any genetic background tested. In the original genetic background, only the Indy mutation associated with altered RNA expression extended lifespan in male flies. However, this effect was abolished by backcrossing into standard outbred genetic backgrounds, and was associated with an unidentified locus on the X chromosome. The original Indy line with long-lived males is infected by the cytoplasmic symbiont Wolbachia, and the longevity of Indy males disappeared after tetracycline clearance of this endosymbiont. These findings underscore the critical importance of standardisation of genetic background and of cytoplasm in genetic studies of lifespan, and show that the lifespan extension previously claimed for Indy mutants was entirely attributable to confounding variation from these two sources. In addition, we saw no effects on lifespan of expression knockdown of the Indy orthologues nac-2 and nac-3 in the nematode Caenorhabditis elegans.

Dietary sodium modulation of aldosterone activation and renal function during the progression of experimental heart failure.

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Miller, Wayne L; Borgeson, Daniel D; Grantham, J Aaron; Luchner, Andreas; Redfield, Margaret M; Burnett, John C

2015-02-01

Aldosterone activation is central to the sodium–fluid retention that marks the progression of heart failure (HF). The actions of dietary sodium restriction, a mainstay in HF management, on cardiorenal and neuroendocrine adaptations during the progression of HF are poorly understood. The study aim was to assess the role of dietary sodium during the progression of experimental HF. Experimental HF was produced in a canine model by rapid right ventricular pacing which evolves from early mild HF to overt, severe HF. Dogs were fed one of three diets: (i) high sodium [250 mEq (5.8 g) per day, n =6]; (ii) standard sodium [58 mEq (1.3 g) per day, n =6]; and (iii) sodium restriction [11 mEq (0.25 g) per day, n =6]. During the 38-day study, haemodynamics, renal function, plasma renin activity (PRA), and aldosterone were measured. Changes in haemodynamics at 38 days were similar in all three groups, as were changes in renal function. Aldosterone activation was demonstrated in all three groups; however, dietary sodium restriction, in contrast to high sodium, resulted in early (10 days) activation of PRA and aldosterone. High sodium demonstrated significant suppression of aldosterone activation over the course of HF progression. Excessive dietary sodium restriction particularly in early stage HF results in early aldosterone activation, while normal and excess sodium intake are associated with delayed or suppressed activation. These findings warrant evaluation in humans to determine if dietary sodium manipulation, particularly during early stage HF, may have a significant impact on neuroendocrine disease progression.

Conserved and differential effects of dietary energy intake on the hippocampal transcriptomes of females and males.

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Bronwen Martin

2008-06-01

Full Text Available The level of dietary energy intake influences metabolism, reproductive function, the development of age-related diseases, and even cognitive behavior. Because males and females typically play different roles in the acquisition and allocation of energy resources, we reasoned that dietary energy intake might differentially affect the brains of males and females at the molecular level. To test this hypothesis, we performed a gene array analysis of the hippocampus in male and female rats that had been maintained for 6 months on either ad libitum (control, 20% caloric restriction (CR, 40% CR, intermittent fasting (IF or high fat/high glucose (HFG diets. These diets resulted in expected changes in body weight, and circulating levels of glucose, insulin and leptin. However, the CR diets significantly increased the size of the hippocampus of females, but not males. Multiple genes were regulated coherently in response to energy restriction diets in females, but not in males. Functional physiological pathway analyses showed that the 20% CR diet down-regulated genes involved in glycolysis and mitochondrial ATP production in males, whereas these metabolic pathways were up-regulated in females. The 40% CR diet up-regulated genes involved in glycolysis, protein deacetylation, PGC-1alpha and mTor pathways in both sexes. IF down-regulated many genes in males including those involved in protein degradation and apoptosis, but up-regulated many genes in females including those involved in cellular energy metabolism, cell cycle regulation and protein deacetylation. Genes involved in energy metabolism, oxidative stress responses and cell death were affected by the HFG diet in both males and females. The gender-specific molecular genetic responses of hippocampal cells to variations in dietary energy intake identified in this study may mediate differential behavioral responses of males and females to differences in energy availability.

A Ketogenic Diet Extends Longevity and Healthspan in Adult Mice.

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Roberts, Megan N; Wallace, Marita A; Tomilov, Alexey A; Zhou, Zeyu; Marcotte, George R; Tran, Dianna; Perez, Gabriella; Gutierrez-Casado, Elena; Koike, Shinichiro; Knotts, Trina A; Imai, Denise M; Griffey, Stephen M; Kim, Kyoungmi; Hagopian, Kevork; McMackin, Marissa Z; Haj, Fawaz G; Baar, Keith; Cortopassi, Gino A; Ramsey, Jon J; Lopez-Dominguez, Jose Alberto

2017-09-05

Calorie restriction, without malnutrition, has been shown to increase lifespan and is associated with a shift away from glycolysis toward beta-oxidation. The objective of this study was to mimic this metabolic shift using low-carbohydrate diets and to determine the influence of these diets on longevity and healthspan in mice. C57BL/6 mice were assigned to a ketogenic, low-carbohydrate, or control diet at 12 months of age and were either allowed to live their natural lifespan or tested for physiological function after 1 or 14 months of dietary intervention. The ketogenic diet (KD) significantly increased median lifespan and survival compared to controls. In aged mice, only those consuming a KD displayed preservation of physiological function. The KD increased protein acetylation levels and regulated mTORC1 signaling in a tissue-dependent manner. This study demonstrates that a KD extends longevity and healthspan in mice. Copyright © 2017 Elsevier Inc. All rights reserved.

Focal Transplantation of Human iPSC-Derived Glial-Rich Neural Progenitors Improves Lifespan of ALS Mice

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Takayuki Kondo

2014-08-01

Full Text Available Transplantation of glial-rich neural progenitors has been demonstrated to attenuate motor neuron degeneration and disease progression in rodent models of mutant superoxide dismutase 1 (SOD1-mediated amyotrophic lateral sclerosis (ALS. However, translation of these results into a clinical setting requires a renewable human cell source. Here, we derived glial-rich neural progenitors from human iPSCs and transplanted them into the lumbar spinal cord of ALS mouse models. The transplanted cells differentiated into astrocytes, and the treated mouse group showed prolonged lifespan. Our data suggest a potential therapeutic mechanism via activation of AKT signal. The results demonstrated the efficacy of cell therapy for ALS by the use of human iPSCs as cell source.

Stress, emotional eating behaviour and dietary patterns in children.

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Michels, Nathalie; Sioen, Isabelle; Braet, Caroline; Eiben, Gabriele; Hebestreit, Antje; Huybrechts, Inge; Vanaelst, Barbara; Vyncke, Krishna; De Henauw, Stefaan

2012-12-01

Psychological stress has been suggested to change dietary pattern towards more unhealthy choices and as such to contribute to overweight. Emotional eating behaviour could be an underlying mediating mechanism. The interrelationship between stress, emotional eating behaviour and dietary patterns has only rarely been examined in young children. Nevertheless, research in children is pivotal as the foundations of dietary habits are established starting from childhood and may track into adulthood. In 437 children (5-12years) of the ChiBS study, stress was measured by questionnaires on stressful events, emotions (happy, angry, sad, anxious) and problems (emotional, peer, conduct and hyperactivity). Data were collected on children's emotional eating behaviour and also on dietary patterns: frequency of fatty foods, sweet foods, snacks (fat and sweet), fruit and vegetables. Stressful events, negative emotions and problems were positively associated with emotional eating. Positive associations were observed between problems and both sweet and fatty foods consumption. Negative associations were observed between events and fruit and vegetables consumption. Overall, stress was associated with emotional eating and a more unhealthy dietary pattern and could thus contribute to the development of overweight, also in children. Nevertheless, emotional eating behaviour was not observed to mediate the stress-diet relation. Copyright © 2012 Elsevier Ltd. All rights reserved.

The mediational significance of negative/depressive affect in the relationship of childhood maltreatment and eating disorder features in adolescent psychiatric inpatients.

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Hopwood, C J; Ansell, E B; Fehon, D C; Grilo, C M

2011-03-01

Childhood maltreatment is a risk factor for eating disorder and negative/depressive affect appears to mediate this relation. However, the specific elements of eating- and body-related psychopathology that are influenced by various forms of childhood maltreatment remain unclear, and investigations among adolescents and men/boys have been limited. This study investigated the mediating role of negative affect/depression across multiple types of childhood maltreatment and eating disorder features in hospitalized adolescent boys and girls. Participants were 148 adolescent psychiatric inpatients who completed an assessment battery including measures of specific forms of childhood maltreatment (sexual, emotional, and physical abuse), negative/depressive affect, and eating disorder features (dietary restriction, binge eating, and body dissatisfaction). Findings suggest that for girls, negative/depressive affect significantly mediates the relationships between childhood maltreatment and eating disorder psychopathology, although effects varied somewhat across types of maltreatment and eating disorder features. Generalization of mediation effects to boys was limited.

Surveying Parental Mediation: Connections, Challenges and Questions for Media Literacy

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Mendoza, Kelly

2009-01-01

This paper examines three strategies of parental mediation--coviewing, restrictive mediation, and active mediation--in order to make connections, challenge, and raise questions for media literacy. Coviewing, whether it is intentional practice, or whether it functions to promote media literacy, is explored. Restrictive mediation, how it connects to…

Running on empty: does mitochondrial DNA mutation limit replicative lifespan in yeast?: Mutations that increase the division rate of cells lacking mitochondrial DNA also extend replicative lifespan in Saccharomyces cerevisiae.

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Dunn, Cory D

2011-10-01

Mitochondrial DNA (mtDNA) mutations escalate with increasing age in higher organisms. However, it has so far been difficult to experimentally determine whether mtDNA mutation merely correlates with age or directly limits lifespan. A recent study shows that budding yeast can also lose functional mtDNA late in life. Interestingly, independent studies of replicative lifespan (RLS) and of mtDNA-deficient cells show that the same mutations can increase both RLS and the division rate of yeast lacking the mitochondrial genome. These exciting, parallel findings imply a potential causal relationship between mtDNA mutation and replicative senescence. Furthermore, these results suggest more efficient methods for discovering genes that determine lifespan. Copyright © 2011 WILEY Periodicals, Inc.

Rec-8 dimorphism affects longevity, stress resistance and X-chromosome nondisjunction in C. elegans, and replicative lifespan in yeast

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Srinivas eAyyadevara

2014-08-01

Full Text Available A quantitative trait locus (QTL in the nematode C. elegans, lsq4, was recently implicated by mapping longevity genes. QTLs for lifespan and 3 stress-resistance traits coincided within a span of <300 kbp, later narrowed to <200 kbp. A single gene in this interval is now shown to modulate all lsq4-associated traits. Full-genome analysis of transcript levels indicates that lsq4 contains a dimorphic gene governing expression of sperm-specific genes, suggesting effects on spermatogenesis. Quantitation of allele-specific transcripts encoded within the lsq4 interval revealed significant, 2- to 15-fold expression differences for 10 of 33 genes. Fourteen genes, implicated by both position and expression, were tested for RNA-interference effects on QTL-linked traits. In a strain carrying the shorter-lived allele, knockdown of rec-8 (encoding a meiotic cohesin reduced its transcripts 4-fold, to a level similar to the longer-lived strain, and extended lifespan 25–26% whether begun before fertilization or at maturity. The short-lived lsq4 allele also conferred sensitivity to oxidative and thermal stresses, and lower male frequency, traits reversed uniquely by rec-8 knockdown. A strain bearing the longer-lived lsq4 allele, differing from the short-lived strain at <0.3% of its genome, derived no lifespan or stress-survival benefit from rec-8 knockdown. We consider two possible explanations: high rec-8 expression may include increased leaky expression in mitotic cells, leading to deleterious destabilization of somatic genomes; or REC-8 may act entirely in germ-line meiotic cells to reduce aberrations such as nondisjunction, thereby blunting a stress-resistance response mediated by innate immunity. Replicative lifespan was extended 20% in haploid S. cerevisiae (BY4741 by deletion of REC8, orthologous to nematode rec-8, implying that REC8 disruption of mitotic-cell survival is widespread, reflecting antagonistic pleiotropy and/or balancing selection.

The effect of protein restriction on the progression of renal insufficiency

International Nuclear Information System (INIS)

Ihle, B.U.; Becker, G.J.; Whitworth, J.A.; Charlwood, R.A.; Kincaid-Smith, P.S.

1989-01-01

Dietary protein intake may be an important determinant of the rate of decline in renal function in patients with chronic renal insufficiency. We conducted a prospective, randomized study of the efficacy of protein restriction in slowing the rate of progression of renal impairment. The study lasted 18 months and included 64 patients with serum creatinine concentrations ranging from 350 to 1000 micromol per liter. The patients were randomly assigned to follow either a regular diet or an isocaloric protein-restricted diet (0.4 g of protein per kilogram of the body weight per day). Blood-pressure levels and the balance between calcium and phosphate were similar in the two groups. End-stage renal failure developed in 9 of the 33 patients (27 percent) who followed the regular diet during the study, as compared with 2 of the 31 patients (6 percent) who followed the protein-restricted diet (P less than 0.05). The mean (+/- SE) glomerular filtration rate, as measured by the clearance of 51Cr bound to EDTA, fell from 0.25 +/- 0.03 to 0.10 +/- 0.05 ml per second (P less than 0.01) in the group on the regular diet, whereas it fell from 0.23 +/- 0.04 to 0.20 +/- 0.05 ml per second (P not significant) in the group on the protein-restricted diet. We conclude that dietary protein restriction is effective in slowing the rate of progression of chronic renal failure

Dietary carbohydrates impair the protective effect of protein restriction against diabetes in NZO mice used as a model of type 2 diabetes.

Science.gov (United States)

Laeger, Thomas; Castaño-Martinez, Teresa; Werno, Martin W; Japtok, Lukasz; Baumeier, Christian; Jonas, Wenke; Kleuser, Burkhard; Schürmann, Annette

2018-06-01

Low-protein diets are well known to improve glucose tolerance and increase energy expenditure. Increases in circulating fibroblast growth factor 21 (FGF21) have been implicated as a potential underlying mechanism. We aimed to test whether low-protein diets in the context of a high-carbohydrate or high-fat regimen would also protect against type 2 diabetes in New Zealand Obese (NZO) mice used as a model of polygenetic obesity and type 2 diabetes. Mice were placed on high-fat diets that provided protein at control (16 kJ%; CON) or low (4 kJ%; low-protein/high-carbohydrate [LP/HC] or low-protein/high-fat [LP/HF]) levels. Protein restriction prevented the onset of hyperglycaemia and beta cell loss despite increased food intake and fat mass. The effect was seen only under conditions of a lower carbohydrate/fat ratio (LP/HF). When the carbohydrate/fat ratio was high (LP/HC), mice developed type 2 diabetes despite the robustly elevated hepatic FGF21 secretion and increased energy expenditure. Prevention of type 2 diabetes through protein restriction, without lowering food intake and body fat mass, is compromised by high dietary carbohydrates. Increased FGF21 levels and elevated energy expenditure do not protect against hyperglycaemia and type 2 diabetes per se.

Embryonic expression of shuttle craft, a Drosophila gene involved in neuron development, is associated with adult lifespan.

Science.gov (United States)

Roshina, Natalia V; Symonenko, Alexander V; Krementsova, Anna V; Trostnikov, Mikhail V; Pasyukova, Elena G

2014-12-01

Despite the progress in aging research that highlights the role of the nervous system in longevity, whether genes that control development and consequently structure of the nervous system affect lifespan is unclear. We demonstrated that a mutation inshuttle craft, a gene involved in the nervous system development, increased the lifespan of unmated females and decreased the lifespan of mated females, without affecting males. Precise reversions of the mutation lead to the restoration of the lifespan specific to control females. In mutant unmated females, increased lifespan was associated with elevated locomotion at older ages, indicating slowed aging. In mutant mated females, reproduction was decreased compared to controls, indicating a lack of tradeoff between this trait and lifespan. No differences in shuttle craft transcription were observed between whole bodies, ovaries, and brains of mutant and control females of different ages, either unmated or mated. The amount of shuttle craft transcript appeared to be substantially decreased in mutant embryos. Our results demonstrated that a gene that regulates development of the nervous system might also influence longevity, and thus expanded the spectrum of genes involved in lifespan control. We hypothesize that this "carry-over" effect might be the result of transcription regulation in embryos.

Lifespan and reproduction of isoclonal individual E.coli in different environments

DEFF Research Database (Denmark)

Jouvet, Lionel; Steiner, Ulrich

Lifespan and reproduction are key fitness components, both of which are influences by genetics and the environment. Tracking large numbers of genotypically known individuals throughout their lives in known environments has been challenging. Here we show for isogenic individual E. coli bacteria...... under controlled environments how demographic parameters and distributions in reproduction and survival change across environments. We achieve this by using a microfluidic device that traps thousands of individual E. coli cells and tracks their division (reproduction) over their lifespan. Our results...

Forever young: SIRT3 a shield against mitochondrial meltdown, aging, and neurodegeneration

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Brad eKincaid

2013-09-01

Full Text Available Caloric restriction, fasting, and exercise have long been recognized for their neuroprotective and lifespan-extending properties; however, the underlying mechanisms of these phenomena remain elusive. Such extraordinary benefits might be linked to the activation of sirtuins. In mammals, the sirtuin family has seven members (SIRT1-7, which diverge in tissue distribution, subcellular localization, enzymatic activity and targets. SIRT1, SIRT2, and SIRT3 have deacetylase activity. Their dependence on NAD+ directly links their activity to the metabolic status of the cell. High NAD+ levels convey neuroprotective effects, possibly via activation of sirtuin family members. Mitochondrial sirtuin 3 (SIRT3 has received much attention for its role in metabolism and aging. Specific small nucleotide polymorphisms (SNPs in Sirt3 are linked to increased human lifespan. SIRT3 mediates the adaptation of increased energy demand during caloric restriction, fasting and exercise to increased production of energy equivalents. SIRT3 deacetylates and activates mitochondrial enzymes involved in fatty acid β-oxidation, amino acid metabolism, the electron transport chain, and antioxidant defenses. As a result, the mitochondrial energy metabolism increases. In addition, SIRT3 prevents apoptosis by lowering reactive oxygen species (ROS and inhibiting components of the mitochondrial permeability transition pore. Mitochondrial deficits associated with aging and neurodegeneration might therefore be slowed or even prevented by SIRT3 activation. In addition, upregulating SIRT3 activity by dietary supplementation of sirtuin activating compounds might promote the beneficial effects of this enzyme. The goal of this review is to summarize emerging data supporting a neuroprotective action of SIRT3 against Alzheimer’s disease (AD, Huntington’s disease (HD, Parkinson’s disease (PD and amyotrophic lateral sclerosis (ALS.

Toward an understanding of late life suicidal behavior: the role of lifespan developmental theory.

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Fiske, Amy; O'Riley, Alisa A

2016-01-01

Suicidal behavior in late life differs in important ways from suicidal behavior that occurs earlier in the lifespan, suggesting the possibility of developmental differences in the etiology of suicidal behavior. This paper examines late life suicidal behavior within the context of lifespan developmental theory. This paper presents a conceptual framework for using lifespan developmental theory to better understand late life suicidal behavior. We argue that the motivational theory of lifespan development, which focuses on control, is particularly relevant to late life suicide. This theory posits that opportunities to exert control over important aspects of one's life diminish in late life as a result of declines in physical functioning and other factors, and that successful aging is associated with adaptive regulation of this developmental change. Although continued striving to meet goals is normative throughout the lifespan, most individuals also increase the use of compensatory strategies in old age or when faced with a decline in functioning. We propose that individuals who do not adapt to developmental changes by altering their strategies for exerting control will be at risk for suicidal behavior in late life. This paper reviews evidence that supports the importance of control with respect to suicidal outcomes in older adults, as well as findings regarding specific types of control strategies that may be related to suicide risk in older adults with health-related limitations. Although suicidal behavior is not a normal part of aging, the application of lifespan developmental theory may be useful in understanding and potentially preventing suicide among older adults.

How parental dietary behavior and food parenting practices affect children's dietary behavior. Interacting sources of influence?

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Larsen, Junilla K; Hermans, Roel C J; Sleddens, Ester F C; Engels, Rutger C M E; Fisher, Jennifer O; Kremers, Stef P J

2015-06-01

Until now, the literatures on the effects of food parenting practices and parents' own dietary behavior on children's dietary behavior have largely been independent from one another. Integrating findings across these areas could provide insight on simultaneous and interacting influences on children's food intake. In this narrative review, we provide a conceptual model that bridges the gap between both literatures and consists of three main hypotheses. First, parental dietary behavior and food parenting practices are important interactive sources of influence on children's dietary behavior and Body Mass Index (BMI). Second, parental influences are importantly mediated by changes in the child's home food environment. Third, parenting context (i.e., parenting styles and differential parental treatment) moderates effects of food parenting practices, whereas child characteristics (i.e., temperament and appetitive traits) mainly moderate effects of the home food environment. Future studies testing (parts of) this conceptual model are needed to inform effective parent-child overweight preventive interventions. Copyright © 2015 Elsevier Ltd. All rights reserved.

Brain IGF-1 receptors control mammalian growth and lifespan through a neuroendocrine mechanism.

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Laurent Kappeler

2008-10-01

Full Text Available Mutations that decrease insulin-like growth factor (IGF and growth hormone signaling limit body size and prolong lifespan in mice. In vertebrates, these somatotropic hormones are controlled by the neuroendocrine brain. Hormone-like regulations discovered in nematodes and flies suggest that IGF signals in the nervous system can determine lifespan, but it is unknown whether this applies to higher organisms. Using conditional mutagenesis in the mouse, we show that brain IGF receptors (IGF-1R efficiently regulate somatotropic development. Partial inactivation of IGF-1R in the embryonic brain selectively inhibited GH and IGF-I pathways after birth. This caused growth retardation, smaller adult size, and metabolic alterations, and led to delayed mortality and longer mean lifespan. Thus, early changes in neuroendocrine development can durably modify the life trajectory in mammals. The underlying mechanism appears to be an adaptive plasticity of somatotropic functions allowing individuals to decelerate growth and preserve resources, and thereby improve fitness in challenging environments. Our results also suggest that tonic somatotropic signaling entails the risk of shortened lifespan.

Dietary n-3 PUFA affect TcR-mediated activation of purified murine T cells and accessory cell function in co-cultures

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CHAPKIN, R S; ARRINGTON, J L; APANASOVICH, T V; CARROLL, R J; MCMURRAY, D N

2002-01-01

Diets enriched in n-3 polyunsaturated fatty acids (PUFA) suppress several functions of murine splenic T cells by acting directly on the T cells and/or indirectly on accessory cells. In this study, the relative contribution of highly purified populations of the two cell types to the dietary suppression of T cell function was examined. Mice were fed diets containing different levels of n-3 PUFA; safflower oil (SAF; control containing no n-3 PUFA), fish oil (FO) at 2% and 4%, or 1% purified docosahexaenoic acid (DHA) for 2 weeks. Purified (>90%) T cells were obtained from the spleen, and accessory cells (>95% adherent, esterase-positive) were obtained by peritoneal lavage. Purified T cells or accessory cells from each diet group were co-cultured with the alternative cell type from every other diet group, yielding a total of 16 different co-culture combinations. The T cells were stimulated with either concanavalin A (ConA) or antibodies to the T cell receptor (TcR)/CD3 complex and the costimulatory molecule CD28 (αCD3/αCD28), and proliferation was measured after four days. Suppression of T cell proliferation in the co-cultures was dependent upon the dose of dietary n-3 PUFA fed to mice from which the T cells were derived, irrespective of the dietary treatment of accessory cell donors. The greatest dietary effect was seen in mice consuming the DHA diet (P = 0·034 in the anova; P = 0·0053 in the Trend Test), and was observed with direct stimulation of the T cell receptor and CD28 costimulatory ligand, but not with ConA. A significant dietary effect was also contributed accessory cells (P = 0·033 in the Trend Test). We conclude that dietary n-3 PUFA affect TcR-mediated by T cell activation by both direct and indirect (accessory cell) mechanisms. PMID:12296847

The effects of graded levels of calorie restriction: III. Impact of short term calorie and protein restriction on mean daily body temperature and torpor use in the C57BL/6 mouse

Science.gov (United States)

Mitchell, Sharon E.; Delville, Camille; Konstantopedos, Penelope; Derous, Davina; Green, Cara L.; Chen, Luonan; Han, Jing-Dong J.; Wang, Yingchun; Promislow, Daniel E.L.; Douglas, Alex; Lusseau, David; Speakman, John R.

2015-01-01

A commonly observed response in mammals to calorie restriction (CR) is reduced body temperature (Tb). We explored how the Tb of male C57BL/6 mice responded to graded CR (10 to 40%), compared to the response to equivalent levels of protein restriction (PR) over 3 months. Under CR there was a dynamic change in daily Tb over the first 30–35 days, which stabilized thereafter until day 70 after which a further decline was noted. The time to reach stability was dependent on restriction level. Body mass negatively correlated with Tb under ad libitum feeding and positively correlated under CR. The average Tb over the last 20 days was significantly related to the levels of body fat, structural tissue, leptin and insulin-like growth factor-1. Some mice, particularly those under higher levels of CR, showed periods of daily torpor later in the restriction period. None of the changes in Tb under CR were recapitulated by equivalent levels of PR. We conclude that changes in Tb under CR are a response only to the shortfall in calorie intake. The linear relationship between average Tb and the level of restriction supports the idea that Tb changes are an integral aspect of the lifespan effect. PMID:26286956

Dietary Composition Independent of Weight Loss in the Management of Non-Alcoholic Fatty Liver Disease

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Tannaz Eslamparast

2017-07-01

Full Text Available Poor dietary composition is an important factor in the progression of non-alcoholic fatty liver disease (NAFLD. The majority of NAFLD patients follow diets with overconsumption of simple carbohydrates, total and saturated fat, with reduced intake of dietary fiber and omega-3 rich foods. Although lifestyle modifications including weight loss and exercise remain the keystone of NAFLD management, modifying dietary composition with or without a calorie-restricted diet may also be a feasible and sustainable strategy for NAFLD treatment. In the present review article, we highlight the potential therapeutic role of a “high quality healthy diet” to improve hepatic steatosis and metabolic dysfunction in patients with NAFLD, independent of caloric restriction and weight loss. We provide a literature review evaluating the evidence behind dietary components including fiber-, meat- and omega-3-rich diets and, pending further evidence, we concur with the EASL-EASD-EASO Clinical Guidelines recommendation of the Mediterranean diet as the diet of choice in these patients.

Can the gastrointestinal microbiota be modulated by dietary fibre to treat obesity?

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Davis, H C

2018-05-01

Recent research suggests that the human gastrointestinal microbiota is greatly involved in yielding, storing and expending energy from the diet; therefore, it may be a further factor in linking diet to obesity. The gut microbial composition is affected by diet throughout the human lifespan, and is highly dynamic and efficient in response to dietary alterations in particular to dietary fibre intake. Short-chained fatty acids (SCFA) are the bi-product of fibre fermentation and have both obesogenic and anti-obesogenic properties. The production of specific forms of SCFAs depends on the microbes available in the gut and the type of fibre ingested. The gut microbiome associated with healthy lean individuals has a higher microbial biodiversity and a greater Bacteroidete to Firmicute ratio compared to the obese individuals associated with microbiome. These gut microbial associations are similar to those seen in individuals with high and low dietary fibre intakes, respectively. Metabolites generated by Bacteroidetes and Firmicutes include the three main SCFA related to obesity, namely butyrate, acetate and propionate. However, neither Bacteroidetes nor Firmicutes is purely causative or purely preventative of obesity. More research is crucial in linking the various types of fibre with particular SCFA production and the microbiome it promotes before suggesting that dietary fibre modulation of the gut microbiome can treat obesity. However, the long-term dietary trend plays the principal role in assembling the diversity and abundance of gut microbes; thus, a sustained diet high in fibre may help prevent obesity by promoting a microbiome associated with a lean phenotype.

Dietary caffeine, performance and mood: enhancing and restorative effects after controlling for withdrawal reversal.

Science.gov (United States)

James, Jack E; Gregg, M Elizabeth; Kane, Marian; Harte, Frances

2005-01-01

This study aimed to determine whether sustained (i.e. dietary) use of caffeine has net effects on performance and mood compared with sustained abstinence, and whether dietary caffeine restores performance and mood adversely affected by sleep restriction. Participants (n = 96) alternated weekly between ingesting placebo and caffeine (1.75 mg/kg) three times daily for 4 consecutive weeks, while either rested or sleep restricted. Performance involved either a single task requiring sustained vigilance or a varied battery of brief psychomotor and cognitive tasks, and mood was assessed using the Profile of Mood States. Caffeine had no significant net enhancing effects for either performance or mood when participants were rested, and produced no net restorative effects when performance and mood were degraded by sleep restriction. Copyright 2005 S. Karger AG, Basel

Protein restriction does not affect body temperature pattern in female mice.

Science.gov (United States)

Kato, Goro A; Shichijo, Hiroki; Takahashi, Toshihiro; Shinohara, Akio; Morita, Tetsuo; Koshimoto, Chihiro

2017-10-30

Daily torpor is a physiological adaptation in mammals and birds characterized by a controlled reduction of metabolic rate and body temperature during the resting phase of circadian rhythms. In laboratory mice, daily torpor is induced by dietary caloric restriction. However, it is not known which nutrients are related to daily torpor expression. To determine whether dietary protein is a key factor in inducing daily torpor in mice, we fed mice a protein-restricted (PR) diet that included only one-quarter of the amount of protein but the same caloric level as a control (C) diet. We assigned six non-pregnant female ICR mice to each group and recorded their body weights and core body temperatures for 4 weeks. Body weights in the C group increased, but those in the PR group remained steady or decreased. Mice in both groups did not show daily torpor, but most mice in a food-restricted group (n=6) supplied with 80% of the calories given to the C group exhibited decreased body weights and frequently displayed daily torpor. This suggests that protein restriction is not a trigger of daily torpor; torpid animals can conserve their internal energy, but torpor may not play a significant role in conserving internal protein. Thus, opportunistic daily torpor in mice may function in energy conservation rather than protein saving.

Reward speeds up and increases consistency of visual selective attention: a lifespan comparison.

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Störmer, Viola; Eppinger, Ben; Li, Shu-Chen

2014-06-01

Children and older adults often show less favorable reward-based learning and decision making, relative to younger adults. It is unknown, however, whether reward-based processes that influence relatively early perceptual and attentional processes show similar lifespan differences. In this study, we investigated whether stimulus-reward associations affect selective visual attention differently across the human lifespan. Children, adolescents, younger adults, and older adults performed a visual search task in which the target colors were associated with either high or low monetary rewards. We discovered that high reward value speeded up response times across all four age groups, indicating that reward modulates attentional selection across the lifespan. This speed-up in response time was largest in younger adults, relative to the other three age groups. Furthermore, only younger adults benefited from high reward value in increasing response consistency (i.e., reduction of trial-by-trial reaction time variability). Our findings suggest that reward-based modulations of relatively early and implicit perceptual and attentional processes are operative across the lifespan, and the effects appear to be greater in adulthood. The age-specific effect of reward on reducing intraindividual response variability in younger adults likely reflects mechanisms underlying the development and aging of reward processing, such as lifespan age differences in the efficacy of dopaminergic modulation. Overall, the present results indicate that reward shapes visual perception across different age groups by biasing attention to motivationally salient events.

Changes in Atherogenic Dyslipidemia Induced by Carbohydrate Restriction in Men Are Dependent on Dietary Protein Source1234

OpenAIRE

Mangravite, Lara M.; Chiu, Sally; Wojnoonski, Kathleen; Rawlings, Robin S.; Bergeron, Nathalie; Krauss, Ronald M.

2011-01-01

Previous studies have shown that multiple features of atherogenic dyslipidemia are improved by replacement of dietary carbohydrate with mixed sources of protein and that these lipid and lipoprotein changes are independent of dietary saturated fat content. Because epidemiological evidence suggests that red meat intake may adversely affect cardiovascular disease risk, we tested the effects of replacing dietary carbohydrate with beef protein in the context of high- vs. low-saturated fat intake i...

Lymphocyte mediators of delayed hypersensitivity; the early phase cells

Energy Technology Data Exchange (ETDEWEB)

Lefford, M J; McGregor, D D [Trudeau Inst., Saranac Lake, N.Y. (USA)

1978-04-01

Inbred rats were immunized with living Bacillus Calmette-Guerin (BCG) and lymphocytes which mediate tuberculin DTH and anti-tuberculosis immunity were found 10 days later in the draining lymph nodes, thoracic duct, blood, spleen, and acute peritoneal exudates. The lymphocytes that mediated DTH incorporated /sup 3/HT in vitro, were large in size, sensitive to vinblastine but relatively resistant to irradiation, and had a short effective lifespan in syngeneic recipients. These properties characterize the cells as short-lived, nonrecirculating immunoblasts. In some experimental situations it was possible to dissociate the expression of DTH and immunity following the transfer of sensitized lymphocytes.

Parahippocampal Cortex Mediates the Relationship between Lutein and Crystallized Intelligence in Healthy, Older Adults

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Marta Karolina Zamroziewicz

2016-12-01

Full Text Available Introduction: Although diet has a substantial influence on the aging brain, the relationship between dietary nutrients and aspects of brain health remains unclear. This study examines the neural mechanisms that mediate the relationship between a carotenoid important for brain health across the lifespan, lutein, and crystallized intelligence in cognitively intact older adults. We hypothesized that higher serum levels of lutein are associated with better performance on a task of crystallized intelligence, and that this relationship is mediated by gray matter structure of regions within the temporal cortex. This investigation aims to contribute to a growing line of evidence, which suggests that particular nutrients may slow or prevent aspects of cognitive decline by targeting specific features of brain aging.Methods: We examined 75 cognitively intact adults between the ages of 65 and 75 to investigate the relationship between serum lutein, tests of crystallized intelligence (measured by the Wechsler Abbreviated Scale of Intelligence, and gray matter volume of regions within the temporal cortex. A three-step mediation analysis was implemented using multivariate linear regressions to control for age, sex, education, income, depression status, and body mass index.Results: The mediation analysis revealed that gray matter thickness of one region within the temporal cortex, the right parahippocampal cortex (Brodmann’s Area 34, partially mediates the relationship between serum lutein and crystallized intelligence. Conclusion: These results suggest that the parahippocampal cortex acts as a mediator of the relationship between serum lutein and crystallized intelligence in cognitively intact older adults. Prior findings substantiate the individual relationships reported within the mediation, specifically the links between (i serum lutein and temporal cortex structure, (ii serum lutein and crystallized intelligence, and (iii parahippocampal cortex structure

Vasopressin and oxytocin levels during normal pregnancy: effects of chronic dietary sodium restriction.

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van der Post, J A; van Buul, B J; Hart, A A; van Heerikhuize, J J; Pesman, G; Legros, J J; Steegers, E A; Swaab, D F; Boer, K

1997-03-01

Neurohypophysial hormones are thought to be involved in alterations in fluid balance during pregnancy and delivery. In the course of normal pregnancy intravascular volume is increased whereas sodium restriction is thought to reduce plasma volume and cardiac output. In the present study, we measured the effect of long-term severe sodium restriction on vasopressin (AVP) and oxytocin (OT) levels during normal pregnancy and after delivery. Fifty-nine healthy nulliparous women were randomized either for a low sodium diet (20 mmol sodium daily) or for a normal diet from week 12 of pregnancy onwards. Circulating plasma levels and urinary excretion of AVP and OT, their neurophysins (Np-AVP and Np-OT) and AVP bound to platelets were determined at regular intervals during pregnancy and after delivery. After completion of the study, women on a sodium-restricted diet were compared with control women on a normal diet using repeated measurement ANOVA with adjustment for potentially confounding variables. After randomization, a reduction in urinary sodium excretion of, on average, 40-82% was found. In general, no effect of sodium restriction could be demonstrated on the various parameters (0.53 sodium restriction compared with non-smokers having a normal diet (P = 0.018). For all parameters, clear changes were found in the course of pregnancy and puerperium (P pregnancy. After birth, free plasma AVP, platelet-bound AVP, OT, osmolality, sodium and potassium increased, while Np-AVP and Np-OT decreased. Although elevated Np-AVP and Np-OT levels during pregnancy seem to indicate increased release of neurohypophysial hormones, pregnancy up to 36 weeks of gestation is accompanied by low circulating AVP and OT levels. Long-term severe sodium restriction diminishes urinary AVP excretion in (non-smoking) pregnant women, without changing circulating levels of AVP and OT, despite the known reduction in circulating volume. The reduced circulating (platelet-bound) AVP levels during pregnancy

Short sleep duration and dietary intake: epidemiologic evidence, mechanisms, and health implications

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Links between short sleep duration and obesity, type 2 diabetes, hypertension, and cardiovascular disease may be mediated through changes in dietary intake. This review provides an overview of recent epidemiologic studies on the relations between habitual short sleep duration and dietary intake in a...

How nutritional status, diet and dietary supplements can affect autism. A review.

Science.gov (United States)

Kawicka, Anna; Regulska-Ilow, Bozena

2013-01-01

Autism is a neurodevelopmental disorder with symptoms arising that are apparent throughout the patient's lifespan. Autism Spectrum Disorders (ASD) are characterised by impaired social and communication interactions as well as restricted, repetitive interests and behaviour. Currently in Poland, about 50 000 people suffer from autism, of which 1/5 are children. Epidemiological studies show that the incidence of autism is increasing, which may be due to the diagnostic category of ASD having been developed. Of vital importance in the treatment of autism, is early diagnosis which is conducive to more rapidly improving the quality of patients' health. It is believed that both genetic and environmental factors may affect the development of the disease. Moreover, expert opinion emphasises the importance of making an adequate diagnosis when the first symptoms of autism start appearing which can be both psychological, gastro-intestinal and metabolic ones. Conventional treatment is based on the combination of behavioural and dietary therapy together with pharmacotherapy. For example, adapting an appropriate diet could help alleviate the disease severity, as well as the psychological and gastrointestinal symptoms. Much scientific research has indicated that pathogenesis of autism may have a beginning already in foetal life. During pregnancy, specialists should take special heed of metabolic disorders, which can increase the risk ofASD in children. One of the dietician's tasks are to properly assess the nutritional status of mothers before and during pregnancy, thereby allowing changes in nutrition to be made wherever necessary in order that metabolic indicators be improved. Thus an important part of autism therapy is the improving patient's nutritional status to prevent the onset of gastrointestinal symptoms. Adopting diets and tailored to individual disease symptoms, is linked to the nutritional requirements and food preferences of the patient. Specialists also emphasise that

Maternal amino acid supplementation for intrauterine growth restriction

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Brown, Laura D; Green, Alice S; Limesand, Sean W; Rozance, Paul J

2011-01-01

Maternal dietary protein supplementation to improve fetal growth has been considered as an option to prevent or treat intrauterine growth restriction. However, in contrast to balanced dietary supplementation, adverse perinatal outcomes in pregnant women who received high amounts of dietary protein supplementation have been observed. The responsible mechanisms for these adverse outcomes are unknown. This review will discuss relevant human and animal data to provide the background necessary for the development of explanatory hypotheses and ultimately for the development therapeutic interventions during pregnancy to improve fetal growth. Relevant aspects of fetal amino acid metabolism during normal pregnancy and those pregnancies affected by IUGR will be discussed. In addition, data from animal experiments which have attempted to determine mechanisms to explain the adverse responses identified in the human trials will be presented. Finally, we will suggest new avenues for investigation into how amino acid supplementation might be used safely to treat and/or prevent IUGR. PMID:21196387

Nicotinamide extends replicative lifespan of human cells.

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Kang, Hyun Tae; Lee, Hyung Il; Hwang, Eun Seong

2006-10-01

We found that an ongoing application of nicotinamide to normal human fibroblasts not only attenuated expression of the aging phenotype but also increased their replicative lifespan, causing a greater than 1.6-fold increase in the number of population doublings. Although nicotinamide by itself does not act as an antioxidant, the cells cultured in the presence of nicotinamide exhibited reduced levels of reactive oxygen species (ROS) and oxidative damage products associated with cellular senescence, and a decelerated telomere shortening rate without a detectable increase in telomerase activity. Furthermore, in the treated cells growing beyond the original Hayflick limit, the levels of p53, p21WAF1, and phospho-Rb proteins were similar to those in actively proliferating cells. The nicotinamide treatment caused a decrease in ATP levels, which was stably maintained until the delayed senescence point. Nicotinamide-treated cells also maintained high mitochondrial membrane potential but a lower respiration rate and superoxide anion level. Taken together, in contrast to its demonstrated pro-aging effect in yeast, nicotinamide extends the lifespan of human fibroblasts, possibly through reduction in mitochondrial activity and ROS production.

Repeated intra-specific divergence in lifespan and ageing of African annual fishes along an aridity gradient

DEFF Research Database (Denmark)

Blažek, Radim; Polačik, Matej; Kačer, Petr

2017-01-01

intrinsic lifespans and a greater increase in mortality with age, more pronounced cellular and physiological deterioration (oxidative damage, tumor load), and a faster decline in fertility than populations from wetter regions. This parallel intra-specific divergence in lifespan and ageing was not associated......Lifespan and ageing are substantially modified by natural selection. Across species, higher extrinsic (environmentally-related) mortality (and hence shorter life expectancy) selects for the evolution of more rapid ageing. However, among populations within species, high extrinsic mortality can lead...... to extended lifespan and slower ageing as a consequence of condition-dependent survival. Using within-species contrasts of eight natural populations of Nothobranchius fishes in common garden experiments, we demonstrate that populations originating from dry regions (with short life expectancy) had shorter...

Diet quality and psychosocial mediators in rural African Americans

Science.gov (United States)

PURPOSE: Obesity and its comorbidities, including cardiovascular disease, hypertension, and diabetes, are largely preventable or modifiable through behavioral factors, such as dietary intake. We examined associations among diet quality, dietary intake, and psychosocial mediators of behavioral chan...

Dietary restraint in college women : Fear of an imperfect fat self is stronger than hope of a perfect thin self

NARCIS (Netherlands)

Dalley, Simon E.; Toffanin, Paolo; Pollet, Thomas V.

We predicted that the perceived likelihood of acquiring a hoped-for thin self would mediate perfectionistic strivings on dietary restraint, and that the perceived likelihood of acquiring a feared fat self would mediate perfectionistic concerns on dietary restraint. We also predicted that the

Dietary restraint in college women: Fear of an imperfect fat self is stronger than hope of a perfect thin self

NARCIS (Netherlands)

Dalley, S.E.; Toffanin, P.; Pollet, T.V.

2012-01-01

We predicted that the perceived likelihood of acquiring a hoped-for thin self would mediate perfectionistic strivings on dietary restraint, and that the perceived likelihood of acquiring a feared fat self would mediate perfectionistic concerns on dietary restraint. We also predicted that the

Maternal dietary n-6 polyunsaturated fatty acid deprivation does not exacerbate post-weaning reductions in arachidonic acid and its mediators in the mouse hippocampus.

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Alashmali, Shoug M; Kitson, Alex P; Lin, Lin; Lacombe, R J Scott; Bazinet, Richard P

2017-09-13

The present study examines how lowering maternal dietary n-6 polyunsaturated fatty acids (PUFA) (starting from pregnancy) compared to offspring (starting from post-weaning) affect the levels of n-6 and n-3 fatty acids in phospholipids (PL) and lipid mediators in the hippocampus of mice. Pregnant mice were randomly assigned to consume either a deprived or an adequate n-6 PUFA diet during pregnancy and lactation (maternal exposure). On postnatal day (PND) 21, half of the male pups were weaned onto the same diet as their dams, and the other half were switched to the other diet for 9 weeks (offspring exposure). At PND 84, upon head-focused high-energy microwave irradiation, hippocampi were collected for PL fatty acid and lipid mediator analyses. Arachidonic acid (ARA) concentrations were significantly decreased in both total PL and PL fractions, while eicosapentaenoic acid (EPA) concentrations were increased only in PL fractions upon n-6 PUFA deprivation of offspring, regardless of maternal exposure. Several ARA-derived eicosanoids were reduced, while some of the EPA-derived eicosanoids were elevated by n-6 PUFA deprivation in offspring. There was no effect of diet on docosahexaenoic acid (DHA) or DHA-derived docosanoids concentrations under either maternal or offspring exposure. These results indicate that the maternal exposure to dietary n-6 PUFA may not be as important as the offspring exposure in regulating hippocampal ARA and some lipid mediators. Results from this study will be helpful in the design of experiments aimed at testing the significance of altering brain ARA levels over different stages of life.

Energy restriction during childhood and early adulthood and ovarian cancer risk

NARCIS (Netherlands)

Schouten, L.J.; Dijk, B.A.C. van; Lumey, L.; Goldbohm, R.A.; Brandt, P.A. van den

2011-01-01

Dietary energy restriction may protect against cancer. In parts of the Netherlands, mostly in larger cities, periods of chronically impaired nutrition and even severe famine (Hunger Winter 1944-1945) existed during the 1930s and World War II (1940-1945). We studied the association between energy

Focus on opportunities as a mediator of the relationship between business owners' age and venture growth

NARCIS (Netherlands)

Gielnik, Michael M.; Zacher, Hannes; Frese, Michael

Combining upper echelons and lifespan theories, we investigated the mediating effect of focus on opportunities on the negative relationship between business owners' age and venture growth. We also expected that mental health moderates the negative relationship between business owners' age and focus

Colon preneoplasia after carcinogen exposure is enhanced and colonic serotonergic system is suppressed by food deprivation.

Science.gov (United States)

Kannen, Vinicius; Fernandes, Cleverson R; Stopper, Helga; Zanette, Dalila L; Ferreira, Frederico R; Frajacomo, Fernando T; Carvalho, Milene C; Brandão, Marcus L; Elias Junior, Jorge; Jordão Junior, Alceu Afonso; Uyemura, Sérgio Akira; Waaga-Gasser, Ana Maria; Garcia, Sérgio B

2013-10-04

Calorie restriction regimens usually promote health and extend life-span in mammals. This is partially related to their preventive effects against malignancies. However, certain types of nutritional restriction failed to induce beneficial effects. The American Institute of Nutrition defines calorie restriction as diets which have only 40% fewer calories, but provide normal amounts of necessary food components such as protein, vitamins and minerals; whereas, food restriction means 40% less of all dietary ingredients plus 40% less calories. Our study aimed to test the hypothesis that the latter type of food deprivation (40% less food than consumed by standard fed rats) might increase cancer risk instead of reducing it, as is generally assumed for all dietary restrictive regimens. Since the endogenous modulation of the colon serotonergic system has been observed to play a role during the early steps of carcinogenesis we also investigated whether the serotoninergic system could be involved in the food intake modulation of cancer risk. For this, rats were exposed to a carcinogen and subjected to food deprivation for 56 days. Triglyceride levels and visceral adipose tissue were reduced while hepatic and colonic lipid peroxidation was increased. This dietary restriction also decreased serotonin levels in colon, and gene expression of its intestinal transporter and receptors. Finally, the numbers of preneoplastic lesions in the colon tissue of carcinogen-exposed rats were increased. Our data suggest that food deprivation enhances formation of early tumorigenic lesions by suppressing serotonergic activity in colon tissue. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Fasting or caloric restriction for healthy aging.

Science.gov (United States)

Anton, Stephen; Leeuwenburgh, Christiaan

2013-10-01

Aging is associated with a host of biological changes that contribute to a progressive decline in cognitive and physical function, ultimately leading to a loss of independence, and increased risk of mortality. To date, prolonged caloric restriction (i.e., a reduction in caloric intake without malnutrition) is the only non-genetic intervention that has consistently been found to extend both mean and maximal life span across a variety of species. Most individuals have difficulty sustaining prolonged caloric restriction, which has led to a search for alternative approaches that can produce similar to benefits as caloric restriction. A growing body of evidence indicates that fasting periods and intermittent fasting regimens in particular can trigger similar biological pathways as caloric restriction. For this reason, there is increasing scientific interest in further exploring the biological and metabolic effects of intermittent fasting periods, as well as whether long-term compliance may be improved by this type of dietary approach. This special will highlight the latest scientific findings related to the effects of both caloric restriction and intermittent fasting across various species including yeast, fruit flies, worms, rodents, primates, and humans. A specific emphasis is placed on translational research with findings from basic bench to bedside reviewed and practical clinical implications discussed. Copyright © 2013 Elsevier Inc. All rights reserved.

Applying a Lifespan Developmental Perspective to Chronic Pain: Pediatrics to Geriatrics.

Science.gov (United States)

Walco, Gary A; Krane, Elliot J; Schmader, Kenneth E; Weiner, Debra K

2016-09-01

An ideal taxonomy of chronic pain would be applicable to people of all ages. Developmental sciences focus on lifespan developmental approaches, and view the trajectory of processes in the life course from birth to death. In this article we provide a review of lifespan developmental models, describe normal developmental processes that affect pain processing, and identify deviations from those processes that lead to stable individual differences of clinical interest, specifically the development of chronic pain syndromes. The goals of this review were 1) to unify what are currently separate purviews of "pediatric pain," "adult pain," and "geriatric pain," and 2) to generate models so that specific elements of the chronic pain taxonomy might include important developmental considerations. A lifespan developmental model is applied to the forthcoming Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks-American Pain Society Pain Taxonomy to ascertain the degree to which general "adult" descriptions apply to pediatric and geriatric populations, or if age- or development-related considerations need to be invoked. Copyright © 2016. Published by Elsevier Inc.

Activation of endothelial nitric oxide synthase by dietary isoflavones: role of NO in Nrf2-mediated antioxidant gene expression.

Science.gov (United States)

Mann, Giovanni E; Rowlands, David J; Li, Francois Y L; de Winter, Patricia; Siow, Richard C M

2007-07-15

The endothelium plays a key role in the maintenance of vascular homeostasis, and increased oxidative stress in vascular disease leads to reduced nitric oxide bioavailability and impaired endothelium-dependent relaxation of resistance vessels. Although epidemiological evidence suggests that diets containing high amounts of natural antioxidants afford protection against coronary heart disease (CHD), antioxidant supplementation trials have largely reported only marginal health benefits. There is controversy concerning the cardiovascular benefits of prolonged estrogen/progestin or soy isoflavone therapy for postmenopausal women and patients with an increased risk of CHD. Research on the potential health benefits of soy isoflavones and other polyphenols contained in red wine, green and black tea and dark chocolate developed rapidly during the 1990's, and recent clinical trials and studies in animal models and cultured endothelial cells provide important and novel insights into the mechanisms by which dietary polyphenols afford protection against oxidative stress. In this review, we highlight that NO and reactive oxygen radicals may mediate dietary polyphenol induced activation of Nrf2, which in turn triggers antioxidant response element (ARE) driven transcription of phase II detoxifying and antioxidant defense enzymes in vascular cells.

Every-other-day feeding extends lifespan but fails to delay many symptoms of aging in mice

DEFF Research Database (Denmark)

Xie, Kan; Neff, Frauke; Markert, Astrid

2017-01-01

that every-other-day feeding-induced longevity is sufficiently explained by delays in life-limiting neoplastic disorders and is not associated with a more general slowing of the aging process in mice.Dietary restriction can extend the life of various model organisms. Here, Xie et al. show that intermittent...... periods of fasting achieved through every-other-day feeding protect mice against neoplastic disease but do not broadly delay organismal aging in animals....

IGF-1 has sexually dimorphic, pleiotropic, and time-dependent effects on healthspan, pathology, and lifespan.

Science.gov (United States)

Ashpole, Nicole M; Logan, Sreemathi; Yabluchanskiy, Andriy; Mitschelen, Matthew C; Yan, Han; Farley, Julie A; Hodges, Erik L; Ungvari, Zoltan; Csiszar, Anna; Chen, Sixia; Georgescu, Constantin; Hubbard, Gene B; Ikeno, Yuji; Sonntag, William E

2017-04-01

Reduced circulating levels of IGF-1 have been proposed as a conserved anti-aging mechanism that contributes to increased lifespan in diverse experimental models. However, IGF-1 has also been shown to be essential for normal development and the maintenance of tissue function late into the lifespan. These disparate findings suggest that IGF-1 may be a pleiotropic modulator of health and aging, as reductions in IGF-1 may be beneficial for one aspect of aging, but detrimental for another. We postulated that the effects of IGF-1 on tissue health and function in advanced age are dependent on the tissue, the sex of the animal, and the age at which IGF-1 is manipulated. In this study, we examined how alterations in IGF-1 levels at multiple stages of development and aging influence overall lifespan, healthspan, and pathology. Specifically, we investigated the effects of perinatal, post-pubertal, and late-adult onset IGF-1 deficiency using genetic and viral approaches in both male and female igf f/f C57Bl/6 mice. Our results support the concept that IGF-1 levels early during lifespan establish the conditions necessary for subsequent healthspan and pathological changes that contribute to aging. Nevertheless, these changes are specific for each sex and tissue. Importantly, late-life IGF-1 deficiency (a time point relevant for human studies) reduces cancer risk but does not increase lifespan. Overall, our results indicate that the levels of IGF-1 during development influence late-life pathology, suggesting that IGF-1 is a developmental driver of healthspan, pathology, and lifespan.

Identification of Potential Calorie Restriction-Mimicking Yeast Mutants with Increased Mitochondrial Respiratory Chain and Nitric Oxide Levels

Directory of Open Access Journals (Sweden)

Bin Li

2011-01-01

Full Text Available Calorie restriction (CR induces a metabolic shift towards mitochondrial respiration; however, molecular mechanisms underlying CR remain unclear. Recent studies suggest that CR-induced mitochondrial activity is associated with nitric oxide (NO production. To understand the role of mitochondria in CR, we identify and study Saccharomyces cerevisiae mutants with increased NO levels as potential CR mimics. Analysis of the top 17 mutants demonstrates a correlation between increased NO, mitochondrial respiration, and longevity. Interestingly, treating yeast with NO donors such as GSNO (S-nitrosoglutathione is sufficient to partially mimic CR to extend lifespan. CR-increased NO is largely dependent on mitochondrial electron transport and cytochrome c oxidase (COX. Although COX normally produces NO under hypoxic conditions, CR-treated yeast cells are able to produce NO under normoxic conditions. Our results suggest that CR may derepress some hypoxic genes for mitochondrial proteins that function to promote the production of NO and the extension of lifespan.

Avoidant/Restrictive Food Intake Disorder in an 11-Year Old South American Boy: Medical and Cultural Challenges

OpenAIRE

Schermbrucker, Jonah; Kimber, Melissa; Johnson, Natasha; Kearney, Sarah; Couturier, Jennifer

2017-01-01

Avoidant/Restrictive Food Intake Disorder (ARFID) is new in the DSM-5, replacing the DSM-IV-TR diagnosis of Feeding Disorder of Infancy or Early Childhood. ARFID has no age criterion, and therefore addresses eating disturbances across the lifespan. This report illustrates the case of an 11-year-old boy of Colombian ancestry with ARFID and explores the role of culture in the diagnosis of ARFID. To date, literature describing this disorder is limited. ARFID is often seen in the child and adoles...

Effect of dietary molybdenum and sulphur on the copper status of ...

African Journals Online (AJOL)

in all groups receiving supplementary Mo. A dietary supplement of 70 mg Mo for a restricted period is ... Keywords: Sheep nutrition, copper toxicity, molybdenum toxicity, sulphur. ..... observation supports the suggestion by Dick, et af. (1975).

Joint inhibition of TOR and JNK pathways interacts to extend the lifespan of Brachionus manjavacas (Rotifera).

Science.gov (United States)

Snell, Terry W; Johnston, Rachel K; Rabeneck, Brett; Zipperer, Cody; Teat, Stephanie

2014-04-01

The TOR kinase pathway is central in modulating aging in a variety of animal models. The target of rapamycin (TOR) integrates a complex network of signals from growth conditions, nutrient availability, energy status, and physiological stresses and matches an organism's growth rate to the resource environment. Important remaining problems are the identification of the pathways that interact with TOR and their characterization as additive or synergistic. One of the most versatile stress sensors in metazoans is the Jun-N-terminal kinase (JNK) signaling pathway. JNK is an evolutionarily conserved stress-activated protein kinase that is induced by a range of stressors, including UV irradiation, reactive oxygen species, DNA damage, heat, and bacterial antigens. JNK is thought to interact with the TOR pathway, but its effects on TOR are poorly understood. We used the rotifer Brachionus manjavacas as a model animal to probe the regulation of TOR and JNK pathways and explore their interaction. The effect of various chemical inhibitors was examined in life table and stressor challenge experiments. A survey of 12 inhibitors revealed two, rapamycin and JNK inhibitor, that significantly extended lifespan of B. manjavacas. At 1 μM concentration, exposure to rapamycin or JNK inhibitor extended mean rotifer lifespan by 35% and maximum lifespan by 37%. Exposure to both rapamycin and JNK inhibitor simultaneously extended mean rotifer lifespan by 65% more than either alone. Exposure to a combination of rapamycin and JNK inhibitors conveyed greater protection to starvation, UV and osmotic stress than either inhibitor alone. RNAi knockdown of TOR and JNK gene expression was investigated for its ability to extend rotifer lifespan. RNAi knockdown of the TOR gene resulted in 29% extension of the mean lifespan compared to control and knockdown of the JNK gene resulted in 51% mean lifespan extension. In addition to the lifespan, we quantified mitochondria activity using the fluorescent

Ketogenic Diet Reduces Midlife Mortality and Improves Memory in Aging Mice.

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Newman, John C; Covarrubias, Anthony J; Zhao, Minghao; Yu, Xinxing; Gut, Philipp; Ng, Che-Ping; Huang, Yu; Haldar, Saptarsi; Verdin, Eric

2017-09-05

Ketogenic diets recapitulate certain metabolic aspects of dietary restriction such as reliance on fatty acid metabolism and production of ketone bodies. We investigated whether an isoprotein ketogenic diet (KD) might, like dietary restriction, affect longevity and healthspan in C57BL/6 male mice. We find that Cyclic KD, KD alternated weekly with the Control diet to prevent obesity, reduces midlife mortality but does not affect maximum lifespan. A non-ketogenic high-fat diet (HF) fed similarly may have an intermediate effect on mortality. Cyclic KD improves memory performance in old age, while modestly improving composite healthspan measures. Gene expression analysis identifies downregulation of insulin, protein synthesis, and fatty acid synthesis pathways as mechanisms common to KD and HF. However, upregulation of PPARα target genes is unique to KD, consistent across tissues, and preserved in old age. In all, we show that a non-obesogenic ketogenic diet improves survival, memory, and healthspan in aging mice. Published by Elsevier Inc.

Caenorhabditis elegans battling starvation stress: low levels of ethanol prolong lifespan in L1 larvae.

Directory of Open Access Journals (Sweden)

Paola V Castro

Full Text Available The nematode Caenorhabditis elegans arrests development at the first larval stage if food is not present upon hatching. Larvae in this stage provide an excellent model for studying stress responses during development. We found that supplementing starved larvae with ethanol markedly extends their lifespan within this L1 diapause. The effects of ethanol-induced lifespan extension can be observed when the ethanol is added to the medium at any time between 0 and 10 days after hatching. The lowest ethanol concentration that extended lifespan was 1 mM (0.005%; higher concentrations to 68 mM (0.4% did not result in increased survival. In spite of their extended survival, larvae did not progress to the L2 stage. Supplementing starved cultures with n-propanol and n-butanol also extended lifespan, but methanol and isopropanol had no measurable effect. Mass spectrometry analysis of nematode fatty acids and amino acids revealed that L1 larvae can incorporate atoms from ethanol into both types of molecules. Based on these data, we suggest that ethanol supplementation may extend the lifespan of L1 larvae by either serving as a carbon and energy source and/or by inducing a stress response.

Trade-off between reproduction and lifespan of the rotifer Brachionus plicatilis under different food conditions.

Science.gov (United States)

Sun, Yunfei; Hou, Xinying; Xue, Xiaofeng; Zhang, Lu; Zhu, Xuexia; Huang, Yuan; Chen, Yafen; Yang, Zhou

2017-11-13

Phaeocystis globosa, one of the most typical red tide-forming species, is usually mixed in the food composition of rotifers. To explore how rotifers respond by adjusting life history strategy when feeding on different quality foods, we exposed the rotifer Brachionus plicatilis to cultures with 100% Chlorella, a mixture of 50% P. globosa and 50% Chlorella, or 100% P. globosa. Results showed that rotifers exposed to 100% Chlorella or to mixed diets produced more total offspring and had higher age-specific fecundity than those exposed to 100% P. globosa. Food combination significantly affected the net reproduction rates of rotifers. By contrast, rotifers that fed on 100% P. globosa or on mixed diets had a longer lifespan than those fed on 100% Chlorella. The overall performances (combining reproduction and lifespan together) of rotifers cultured in 100% Chlorella or mixed diets were significantly higher than those cultured in 100% P. globosa. In general, Chlorella favors rotifers reproduction at the cost of shorter lifespan, whereas P. globosa tends to extend the lifespan of rotifers with lower fecundity, indicating that trade-off exists between reproduction and lifespan under different food conditions. The present study also suggests that rotifers may have the potential to control harmful P. globosa.

Age-Dependence and Aging-Dependence: Neuronal Loss and Lifespan in a C. elegans Model of Parkinson's Disease.

Science.gov (United States)

Apfeld, Javier; Fontana, Walter

2017-12-23

It is often assumed, but not established, that the major neurodegenerative diseases, such as Parkinson's disease, are not just age-dependent (their incidence changes with time) but actually aging-dependent (their incidence is coupled to the process that determines lifespan). To determine a dependence on the aging process requires the joint probability distribution of disease onset and lifespan. For human Parkinson's disease, such a joint distribution is not available, because the disease cuts lifespan short. To acquire a joint distribution, we resorted to an established C. elegans model of Parkinson's disease in which the loss of dopaminergic neurons is not fatal. We find that lifespan is not correlated with the loss of individual neurons. Therefore, neuronal loss is age-dependent and aging-independent. We also find that a lifespan-extending intervention into insulin/IGF1 signaling accelerates the loss of specific dopaminergic neurons, while leaving death and neuronal loss times uncorrelated. This suggests that distinct and compartmentalized instances of the same genetically encoded insulin/IGF1 signaling machinery act independently to control neurodegeneration and lifespan in C. elegans . Although the human context might well be different, our study calls attention to the need to maintain a rigorous distinction between age-dependence and aging-dependence.

Phylogenetic relationship and Fourier-transform infrared spectroscopy-derived lipid determinants of lifespan parameters in the Saccharomyces cerevisiae yeast.

Science.gov (United States)

Molon, Mateusz; Zebrowski, Jacek

2017-06-01

Yeast ageing has been gaining much attention in gerontology research, yet the process itself is still not entirely clear. One of the constraints related to the use of the Saccharomyces cerevisiae yeast in studies is the ambiguity of the results concerning ageing determinants for different genetic backgrounds. In this paper, we compare reproductive potentials and lifespans of seven widely used haploid laboratory strains differing in daughter cells production capabilities and highlight the importance of choosing an appropriate genotype for the studies on ageing. Moreover, we show here links between post-reproductive lifespan and lipid metabolism, as well as between reproductive potential, reproductive lifespan and phylogenetic relationship. Using FTIR spectroscopy that generated a biochemical fingerprint of cells, coupled with chemometrics, we found that the band of carbonyl (C = O) stretching vibration discriminates the strains according to post-reproductive lifespan. The results indicated that prolonged post-reproductive lifespan was associated with relatively lower amount of fatty acids esterified to phospholipids compared to a free acid pool, thus implying phospholipid metabolism for the post-reproductive lifespan of yeast. In addition, phylogenetic analysis showed a correlation between nucleotide similarity and the reproductive potential or reproductive lifespan, but not to the longevity expressed in time units. © FEMS 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Evolution of product lifespan and implications for environmental assessment and management: a case study of personal computers in higher education.

Science.gov (United States)

Babbitt, Callie W; Kahhat, Ramzy; Williams, Eric; Babbitt, Gregory A

2009-07-01

Product lifespan is a fundamental variable in understanding the environmental impacts associated with the life cycle of products. Existing life cycle and materials flow studies of products, almost without exception, consider lifespan to be constant over time. To determine the validity of this assumption, this study provides an empirical documentation of the long-term evolution of personal computer lifespan, using a major U.S. university as a case study. Results indicate that over the period 1985-2000, computer lifespan (purchase to "disposal") decreased steadily from a mean of 10.7 years in 1985 to 5.5 years in 2000. The distribution of lifespan also evolved, becoming narrower over time. Overall, however, lifespan distribution was broader than normally considered in life cycle assessments or materials flow forecasts of electronic waste management for policy. We argue that these results suggest that at least for computers, the assumption of constant lifespan is problematic and that it is important to work toward understanding the dynamics of use patterns. We modify an age-structured model of population dynamics from biology as a modeling approach to describe product life cycles. Lastly, the purchase share and generation of obsolete computers from the higher education sector is estimated using different scenarios for the dynamics of product lifespan.

The comparative effect of fasting with and without caloric restriction in Rat on oxidative stress parameters

OpenAIRE

Nurina Tyagita; Taufiqurrachman Nasihun; Titiek Sumarawati

2016-01-01

Introduction: Fasting, like Islamic Ramadan Fasting, has been associated with health benefits. Islamic Ramadan fasting, a form of caloric restriction (CR) or alternate day fasting that. Studies suggest a comparable effect of ADF and caloric restriction. Despite the fact that fasting can be considered as a form of dietary restriction, fasters tend to have difficulty to reduce their food intake during non-fasting period by overeating leading to the excessive calorie intake. To compare the effec...

Lifespan-extending effects of royal jelly and its related substances on the nematode Caenorhabditis elegans.

Directory of Open Access Journals (Sweden)

Yoko Honda

Full Text Available One of the most important challenges in the study of aging is to discover compounds with longevity-promoting activities and to unravel their underlying mechanisms. Royal jelly (RJ has been reported to possess diverse beneficial properties. Furthermore, protease-treated RJ (pRJ has additional pharmacological activities. Exactly how RJ and pRJ exert these effects and which of their components are responsible for these effects are largely unknown. The evolutionarily conserved mechanisms that control longevity have been indicated. The purpose of the present study was to determine whether RJ and its related substances exert a lifespan-extending function in the nematode Caenorhabditis elegans and to gain insights into the active agents in RJ and their mechanism of action.We found that both RJ and pRJ extended the lifespan of C. elegans. The lifespan-extending activity of pRJ was enhanced by Octadecyl-silica column chromatography (pRJ-Fraction 5. pRJ-Fr.5 increased the animals' lifespan in part by acting through the FOXO transcription factor DAF-16, the activation of which is known to promote longevity in C. elegans by reducing insulin/IGF-1 signaling (IIS. pRJ-Fr.5 reduced the expression of ins-9, one of the insulin-like peptide genes. Moreover, pRJ-Fr.5 and reduced IIS shared some common features in terms of their effects on gene expression, such as the up-regulation of dod-3 and the down-regulation of dod-19, dao-4 and fkb-4. 10-Hydroxy-2-decenoic acid (10-HDA, which was present at high concentrations in pRJ-Fr.5, increased lifespan independently of DAF-16 activity.These results demonstrate that RJ and its related substances extend lifespan in C. elegans, suggesting that RJ may contain longevity-promoting factors. Further analysis and characterization of the lifespan-extending agents in RJ and pRJ may broaden our understanding of the gene network involved in longevity regulation in diverse species and may lead to the development of nutraceutical

Changes in atherogenic dyslipidemia induced by carbohydrate restriction in men are dependent on dietary protein source.

Science.gov (United States)

Mangravite, Lara M; Chiu, Sally; Wojnoonski, Kathleen; Rawlings, Robin S; Bergeron, Nathalie; Krauss, Ronald M

2011-12-01

Previous studies have shown that multiple features of atherogenic dyslipidemia are improved by replacement of dietary carbohydrate with mixed sources of protein and that these lipid and lipoprotein changes are independent of dietary saturated fat content. Because epidemiological evidence suggests that red meat intake may adversely affect cardiovascular disease risk, we tested the effects of replacing dietary carbohydrate with beef protein in the context of high- vs. low-saturated fat intake in 40 healthy men. After a 3-wk baseline diet [50% daily energy (E) as carbohydrate, 13% E as protein, 15% E as saturated fat], participants consumed for 3 wk each in a randomized crossover design two high-beef diets in which protein replaced carbohydrate (31% E as carbohydrate, 31% E as protein, with 10% E as beef protein). The high-beef diets differed in saturated fat content (8% E vs. 15% E with exchange of saturated for monounsaturated fat). Two-week washout periods were included following the baseline diet period and between the randomized diets periods. Plasma TG concentrations were reduced after the 2 lower carbohydrate dietary periods relative to after the baseline diet period and these reductions were independent of saturated fat intake. Plasma total, LDL, and non-HDL cholesterol as well as apoB concentrations were lower after the low-carbohydrate, low-saturated fat diet period than after the low-carbohydrate, high-saturated fat diet period. Given our previous observations with mixed protein diets, the present findings raise the possibility that dietary protein source may modify the effects of saturated fat on atherogenic lipoproteins.

Nutritional adequacy of dietary intake in women with anorexia nervosa

Science.gov (United States)

Background: Understanding nutrient intake of anorexia nervosa (AN) patients is essential for the establishment of dietary treatment. Design: Women, aged 19 to 30 years, with both restricting and binge purge types of AN, participating in an ecological momentary assessment study, completed three nonc...

The Effect of Post-Reproductive Lifespan on the Fixation Probability of Beneficial Mutations

DEFF Research Database (Denmark)

Giaimo, Stefano; Baudisch, Annette

2015-01-01

Post-reproductive lifespan is a common trait among mammals and is usually considered to be neutral; i.e. with no influence on population dynamics. Here, we explore the role of post-reproductive lifespan in the fixation probability of beneficial genetic variation. We compare two separate, stationary...... populations living in a constant environment that are equivalent except for the average time their respective members spend in the post-reproductive stage of life. Using a recently derived approximation, we show that fixation of a beneficial mutation is more likely in the population with greater post......-reproductive longevity. This finding is surprising, as the population with more prolonged post-reproductive lifespan has smaller effective size and the classic population-genetic model would suggest that decreasing effective size reduces fixation chances of beneficial mutations. Yet, as we explain, in the age...

Dietary pattern, serum magnesium, ferritin, C-reactive protein and anaemia among older people.

Science.gov (United States)

Xu, Xiaoyue; Hall, John; Byles, Julie; Shi, Zumin

2017-04-01

Epidemiological data of dietary patterns and anaemia among older Chinese remains extremely scarce. We examined the association between dietary patterns and anaemia in older Chinese, and to assess whether biomarkers of serum magnesium, C-reactive protein (CRP) and serum ferritin can mediate these associations. We analysed the 2009 China Health and Nutrition Survey data (2401 individuals aged ≥60 years for whom both dietary and biomarker data are available). Dietary data was obtained using 24 h-recall over three consecutive days. Fasting blood samples and anthropometry measurement were also collected. Factor analysis was used to identify dietary patterns. Factor scores representing dietary patterns were used in Poisson regression models to explore the association between each dietary pattern and anaemia. Of the 2401 participants, 18.9% had anaemia, 1.9% had anaemia related to inflammation (AI), and 1.3% had iron-deficiency anaemia (IDA). A traditional dietary pattern (high intake of rice, pork and vegetables) was positively associated with anaemia; a modern dietary pattern (high intake of fruit and fast food) was inversely associated with anaemia. Progressively lower magnesium and BMI levels were associated with increasing traditional dietary quartiles; while a progressively higher magnesium and BMI levels were associated with increasing modern dietary quartiles (p  0.05) in CRP and serum ferritin across quartiles for either dietary pattern. In the fully adjusted model, the prevalence ratio (PR) of anaemia, comparing the fourth quartile to the first quartile, was 1.75 (95% CI: 1.33; 2.29) for a traditional dietary pattern, and 0.89 (95% CI: 0.68; 1.16) for a modern dietary pattern. The association between dietary patterns and anaemia is mediated by serum magnesium. Traditional dietary pattern is associated with a higher prevalence of anaemia among older Chinese. Future studies need to examine whether correcting micronutrient deficiency (e.g. magnesium) by