Effects Of Dietary Restriction Research Articles

Chemosensory and caloric mechanisms influence distinct components of mortality rate

Both caloric and chemosensory mechanisms influence lifespan, but the relative importance of each of these mechanisms in mediating effects of dietary restriction on lifespan has been unclear. Here we demonstrate that chemosensory mechanisms consistently influence initial mortality rate, whereas caloric mechanisms consistently influence age-dependent acceleration of mortality rate. Based on this analysis, life-extending effects of dietary restriction are mediated primarily by caloric mechanisms in rats and nematodes and by both mechanisms in mice and flies.

P.5.f.001 Dietary restriction effects on age induced changes in APP, PS-1 and ADAM mRNA expression

P.5.f.001 Dietary restriction effects on age induced changes in APP, PS-1 and ADAM mRNA expression

Programming Neuroendocrine Stress Axis Activity by Exposure to Glucocorticoids during Postembryonic Development of the Frog, Xenopus laevis

Exposure to elevated glucocorticoids during early mammalian development can have profound, long-term consequences for health and disease. However, it is not known whether such actions occur in nonmammalian species, and if they do, whether the molecular physiological mechanisms are evolutionarily conserved. We investigated the effects of dietary restriction, which elevates endogenous corticosterone (CORT), or exposure to exogenous CORT added to the aquarium water of Xenopus laevis tadpoles on later-life measures of growth, feeding behavior, and neuroendocrine stress axis activity. Dietary restriction of prometamorphic tadpoles reduced body size at metamorphosis, but juvenile frogs increased food intake, showed catch-up growth through 21 d after metamorphosis, and had elevated whole-body CORT content compared with controls. Dietary restriction causes increased CORT in tadpoles, so to mimic this increase, we treated tadpoles with 100 nm CORT or vehicle for 5 or 10 d and then reared juvenile frogs to 2 months after metamorphosis. Treatment with CORT decreased body weight at metamorphosis, but juvenile frogs showed catch-up growth and had elevated basal plasma (CORT). Immunohistochemical analysis showed that CORT exposure as a tadpole led to decreased glucocorticoid receptor immunoreactivity in brain regions involved with stress axis regulation and in the anterior pituitary gland of juvenile frogs. The elevated CORT in juvenile frogs, which could result from decreased negative feedback owing to down-regulation of glucocorticoid receptor, may drive the hyperphagic response. Taken together, our findings suggest that long-term, stable phenotypic changes in response to elevated glucocorticoids early in life are an ancient and conserved feature of the vertebrate lineage.

Aging and dietary restriction effects on ubiquitination, sumoylation, and the proteasome in the heart

Dietary restriction (DR), in the absence of malnutrition, is the only intervention known to reliably increase average and maximal lifespan in a variety of organisms including mammals. Because the effects of DR on the heart are poorly understood, in the present study we examined the effects of DR on the ubiquitin-proteasome pathway (UPP) in the heart. In these studies we observed that DR significantly reduced age-related impairments in proteasome-mediated protein degradation, and reduced age-related increases in ubiquitinated, oxidized, and sumoylated protein in the heart. Interestingly, DR did not significantly increase the expression of 20S proteasome subunits or the proteasome maturation factor (POMP-1). These data demonstrate for the first time the effects of aging and DR on proteasome biogenesis and sumoylation in the heart. Cumulatively, our data indicate that DR has many beneficial effects towards the UPP in the heart, and suggests that a preservation of the UPP may be a potential mechanism by which DR mediates beneficial effects on the cardiovascular system.

Dietary lipoic acid supplementation can mimic or block the effect of dietary restriction on life span

Dietary restriction feeding extends survival in a range of species but a detailed understanding of the underlying mechanism is lacking. There is interest therefore in identifying a more targeted approach to replicate this effect on survival. We report that in rats dietary supplementation with alpha-lipoic acid, has markedly differing effects on lifetime survival depending upon the dietary history of the animal. When animals are switched from DR feeding to ad libitum feeding with a diet supplemented with alpha-lipoic acid, the extended survival characteristic of DR feeding is maintained, even though the animals show accelerated growth. Conversely, switching from ad libitum feeding a diet supplemented with alpha-lipoic acid to DR feeding of the non-supplemented diet, blocks the normal effect of DR to extend survival, even after cessation of lipoic acid supplementation. Unlike the dynamic effect of switching between DR and ad libitum feeding with a non-supplemented diet where the subsequent survival trajectory is determined by the new feeding regime, lipoic acid fixes the survival trajectory to that established by the initial feeding regime. Ad libitum feeding a diet supplemented with lipoic acid can therefore act as mimetic of DR to extend survival.

Vasoprotective effects of resveratrol and SIRT1: attenuation of cigarette smoke-induced oxidative stress and proinflammatory phenotypic alterations

The dietary polyphenolic compound resveratrol, by activating the protein deacetylase enzyme silent information regulator 2/sirtuin 1 (SIRT1), prolongs life span in evolutionarily distant organisms and may mimic the cytoprotective effects of dietary restriction. The present study was designed to elucidate the effects of resveratrol on cigarette smoke-induced vascular oxidative stress and inflammation, which is a clinically highly relevant model of accelerated vascular aging. Cigarette smoke exposure of rats impaired the acetylcholine-induced relaxation of carotid arteries, which could be prevented by resveratrol treatment. Smoking and in vitro treatment with cigarette smoke extract (CSE) increased reactive oxygen species production in rat arteries and cultured coronary arterial endothelial cells (CAECs), respectively, which was attenuated by resveratrol treatment. The smoking-induced upregulation of inflammatory markers (ICAM-1, inducible nitric oxide synthase, IL-6, and TNF-alpha) in rat arteries was also abrogated by resveratrol treatment. Resveratrol also inhibited CSE-induced NF-kappaB activation and inflammatory gene expression in CAECs. In CAECs, the aforementioned protective effects of resveratrol were abolished by knockdown of SIRT1, whereas the overexpression of SIRT1 mimicked the effects of resveratrol. Resveratrol treatment of rats protected aortic endothelial cells against cigarette smoking-induced apoptotic cell death. Resveratrol also exerted antiapoptotic effects in CSE-treated CAECs, which could be abrogated by knockdown of SIRT1. Resveratrol treatment also attenuated CSE-induced DNA damage in CAECs (comet assay). Thus resveratrol and SIRT1 exert antioxidant, anti-inflammatory, and antiapoptotic effects, which protect the endothelial cells against the adverse effects of cigarette smoking-induced oxidative stress. The vasoprotective effects of resveratrol will likely contribute to its antiaging action in mammals and may be especially beneficial in pathophysiological conditions associated with accelerated vascular aging.

Dietary restriction does not prevent nigrostriatal degeneration in the 6-hydroxydopamine model of Parkinson's disease

Chronic reduction of the caloric intake is associated with extended lifespan, in rodents, and has been proposed to counteract neuronal loss in animal models of neurodegeneration. To test this hypothesis, we investigated the effect of dietary restriction (DR) in a rodent model of Parkinson's disease, based on the intrastriatal infusion of 6-hydroxydopamine. We could not confirm the neuroprotective effect of DR previously suggested: histological and behavioral measures indicated similar degrees of dopaminergic neuron loss in rats maintained on DR – for two or eight weeks prior to the lesion – or with free access to food.

Plasma lipid profiles in Nigerians with normal blood pressure, hypertension and other acquired cardiac conditions

The attention of researchers has recently been drawn to the changing lipid pattern in the Nigerian African because of diet and changing lifestyles. With increasing awareness of systemic hypertension and the role of cholesterol in ischaemic heart disease, indiscriminate emphasis has been placed on the reduction of fat intake and total calorie intake in every patient who has any form of heart disease. To assess and demonstrate any association between abnormal lipid profile and some acquired cardiovascular diseases, which confer relevance of dietary cholesterol restriction. A cross-sectional study. Cardiology clinic, University of Benin Teaching Hospital. One hundred and twenty two patients (59 males and 63 females) who attended the cardiology clinic in the month of May 2001. The results revealed significant hyperlipidaemia in three groups of Nigerian patients with acquired heart disease: the hypertensive with or without hypertensive heart disease (HHDx), the patient with ischaemic heart disease (IHD), and those with hypertrophic cardiomyopathy (HCM). Rheumatic heart disease (RHD) and dilated cardiomyopathy (DCM) had lower cholesterol levels than the normotensives. This study has demonstrated that not all acquired cardiovascular diseases are associated with hyperlipidaemia. Intervention studies may therefore be needed to examine the benefits or adverse effects of dietary restriction in such conditions.

Electron paramagnetic resonance analyses of the effect of dietary restriction on salmonella infection in different tissues

Caloric restriction (CR) involves a reduction in caloric intake while maintaining adequate nutrition and preserves the activities of antioxidant enzymes. The aim of the present contribution was study the formation of free radicals in different tissues of mice at 2, 6 and 12 months of age which were fed either with CR or ad libitum, produced by infection with S. Typhimurium determined through electron paramagnetic resonance (EPR).All samples of heart and brain collected depicted the same EPR spectra with a single signal at g=1.99, which corresponds to a free radical. The EPR spectra obtained from liver showed two signals, one of them at g=2.031 which corresponds to the the nitrosyl‐iron complex, this signal show higher intensity in mice fed with RC. Therefore, the production of nitric oxide could be important in the liver when the mice are treated with S. Typhimurium. The signal at g =1.99 correspond to free radical it was observed in muscle samples as well. In the 12 month old mice age different signals were observed, which has been assigned to peroxinitrite (ONOO‐) a molecule that is of great importance during the infection with salmonella.

Effects of selenium supply and dietary restriction on maternal and fetal metabolic hormones in pregnant ewe lambs1

The objective of these studies was to evaluate the effects of dietary restriction and Se on maternal and fetal metabolic hormones. In Exp. 1, pregnant ewe lambs (n = 32; BW = 45.6 +/- 2.3 kg) were allotted randomly to 1 of 4 treatments. Diets contained (DM basis) either no added Se (control), or supranutritional Se added as high-Se wheat at 3.0 mg/kg (Se-wheat), or sodium selenate at 3 (Se3) and 15 (Se15) mg/kg of Se. Diets (DM basis) were similar in CP (15.5%) and ME (2.68 Mcal/kg). Treatments were initiated at 50 +/- 5 d of gestation. The control, Se-wheat, Se3, and Se15 treatments provided 2.5, 75, 75, and 375 microg/kg of BW of Se, respectively. Ewe jugular blood samples were collected at 50, 64, 78, 92, 106, 120, and 134 d of gestation. Fetal serum samples were collected at necropsy on d 134. In Exp. 2, pregnant ewe lambs (n = 36; BW 53.8 +/- 1.3 kg) were allotted randomly to treatments in a 2 x 2 factorial arrangement. Factors were nutrition (control, 100% of requirements vs. restricted nutrition, 60% of control) and dietary Se (adequate Se, 6 microg/kg of BW vs. high Se, 80 microg/kg of BW). Selenium treatments were initiated 21 d before breeding, and nutritional treatments were initiated on d 64 of gestation. Diets were 16% CP and 2.12 Mcal/kg of ME (DM basis). Blood samples were collected from the ewes at 62, 76, 90, 104, 118, 132, and 135 d of gestation. Fetal blood was collected at necropsy on d 135. In Exp.1, dietary Se source and concentration had no effect (P > 0.17) on maternal and fetal serum IGF-I, triiodothyronine (T(3)), or thyroxine (T(4)) concentrations. Selenium supplementation increased (P = 0.06) the T(4):T(3) ratio vs. controls. In Exp. 2, dietary Se had no impact (P > 0.33) on main effect means for maternal and fetal serum IGF-I, T(3), or T(4) concentrations from d 62 to 132; however, at d 135, high-Se ewes had lower (P = 0.01) serum T(4) concentrations than adequate-Se ewes. A nutrition by Se interaction (P = 0.06) was detected for the T(4):T(3) ratios; ewes fed restricted and adequate-Se diets had greater (P = 0.10) T(4):T(3) ratios compared with the other treatments. Nutrient-restricted ewes had lower (P < 0.05) serum IGF-I, T(3), and T(4) concentrations. Fetal serum IGF-I concentrations were lower (P = 0.01) in restricted-vs. control-fed ewes; however, fetal T(3) and T(4) concentrations were unaffected (P > 0.13) by dietary Se or maternal plane of nutrition. These data indicate that dietary Se may alter maternal T(4):T(3) ratios. In addition, nutrient restriction during gestation reduces maternal IGF-I, T(3), and T(4) and fetal IGF-I concentrations.

Dietary restriction reduces the rate of estradiol clearance in sheep (Ovis aries)

Three experiments were designed to test the effect of dietary restriction on clearance of 17beta-estradiol (E(2)) in sheep. A preliminary experiment examined the effect of a 4-d fast on the rate of E(2) clearance in wethers. The second experiment tested the hypothesis that either long-term restriction (7 wk) or a 5-d fast would increase steroid-binding capacity of serum by increasing the concentration of sex hormone-binding globulin (SHBG) in the blood of ovariectomized ewes. In Exp. 3, we hypothesized that nutrition-dependent regulation of E(2) clearance by the liver would result in divergence in biliary extraction of E(2) in fed and fasted wethers receiving comparable levels of exogenous E(2). A marked difference in E(2) clearance between fed and fasted wethers was noted in the preliminary study. Relative to ad libitumfed wethers, a 4-d fast decreased E(2) clearance by 52%. Serum concentrations of SHBG were increased in long-term energy-restricted and fasted ewes, relative to the concentration in maintenancefed ewes (P = 0.015). Furthermore, a 5-d fast nearly doubled serum steroid-binding capacity in wethers. The E(2) concentration in bile was 2 times greater in fasted than in fed wethers. This fasting-dependent increase in biliary E(2) may be reflective of the increased serum E(2) in fasted animals, because each 1 pg/mL increase in serum E(2) increased bile E(2) by 0.86 +/- 0.12 pg/mL, independent of nutrition (P = 0.002). Our results demonstrate that the rate of clearance of E(2) is decreased during nutritional restriction. Additionally, these data indicate that altered SHBG expression, enterohepatic recirculation, or both are involved in the decreased E(2) clearance during dietary restriction.

Dietary restriction inhibits spatial learning ability and hippocampal cell proliferation in rats1

Abstract: We investigated the effect of dietary restriction on spatial learning ability and hippocampal cell proliferation in adult rats using two spatial learning tasks and immunohistochemical staining with 5‐bromo‐2′‐deoxyuridine (BrdU). Sixteen rats were divided into restricted or ad lib feeding groups at 70 days of age, and were trained in the delayed‐matching‐to‐place (DMTP) task (a working memory task) from 93 days of age, and then the Morris water maze task (a reference memory task). Dietary restriction had no effect on the DMTP task with 30 s delay and on the water maze task. However, in the DMTP task with 30 min delay, restricted rats performed significantly more poorly than ad lib rats. Quantitative analysis of hippocampal cell proliferation revealed that the density of newborn cells in restricted rats was significantly lower than that in ad lib rats. These results suggest that a loss of proliferating capacity in the hippocampus may be a candidate for an anatomical and biological basis for the cognitive decline caused by dietary restriction.

Effects of dietary restriction on hematopoietic stem-cell aging are genetically regulated

AbstractDiminished stem-cell functions with age may be a major cause of anemias and other defects. Unfortunately, treatments that increase stem-cell function can also increase the incidence of cancers. Lifelong dietary restriction (DR) is known to decrease spontaneous cancers and lengthen lifespan. This study examines the effect of DR on the ability of bone marrow cells to repopulate irradiated recipients and produce erythrocytes and lymphocytes. In BALB/cByJ (BALB) mice, repopulating abilities decline with age; DR ameliorates this trend. In C57BL/6J (B6) and (BALB × B6) F1 hybrid (F1) mice, repopulating abilities increase with age; DR maintains this increase. Hematopoietic stem cell (HSC) numbers are highly variable in aged BALB mice; however, the observed loss of marrow function results from a major loss in repopulating ability per HSC. DR greatly ameliorates this loss of function with age. In contrast, function per HSC in B6 mice is affected neither by age nor by DR. Thus, DR increases or maintains increased marrow repopulating ability with age in the 3 different genotypes tested, but effects on function per HSC depend on genotype. That DR increases or maintains stem-cell function with age, while decreasing cancer, has far-reaching health implications.

Impact of Dietary Restriction on Peroxidative Effects of Nickel Chloride in Wistar Rats

ABSTRACTThe purpose of this study, carried out in Wistar rats, was to evaluate the protective effect of dietary restriction (performed by intermittent fasting) against oxidative stress induced by a low concentration of nickel chloride in kidney, liver, uterus, and ovary. Lipid peroxidation (TBARS), catalase activity, and the levels of vitamins E and A in the blood were investigated in rats feed for 1 month either daily (N) or 1 day over two (intermittent fasting, IF) and then injected (NNi, IFNi) or not with nickel chloride (30 μmoles/kg body weight/day) for 10 days. Ni induced a significant increase of TBARS in organs of N rats. Intermittent fasting alone or associated to nickel treatment did not result in TBARS change in IF and IFNi rats. Catalase activity levels were found to be similar in N and IF rats. In Ni-treated rats a transient increase of catalase activity appeared at day 1 in the kidney and days 1 and 3 in the liver. Then, catalase activity was found to be inhibited until day 10. In the uterus and ovary, catalase activity was always found to be inhibited. In IFNi rats, no significant increase of catalase activity was observed as compared to IF rats. Vitamin E was inhibited from the 1st to the 10th day in Ni rats, whereas no significant changes were noted in IFNi rats. A moderate decrease of vitamin A was only found at days 1 and 3 in Ni rats. In conclusion, intermittent fasting is able to protect from oxidative stress induced by low concentration of Ni, but catalase and Vitamins E and A do not seem to be involved.

Rhodiola: A Promising Anti-Aging Chinese Herb

Using the fruit fly, Drosophila melanogaster, we investigated the effects of Rhodiola on life-span. Rhodiola is a plant root used in traditional Chinese medicine that may increase an organism's resistance to stress. It has been proposed that Rhodiola can extend longevity and improve health span by alleviating oxidative stress. Rhodiola supplied every other day at 30 mg/mL significantly increased the lifespan of Drosophila melanogaster. When comparing the distribution of deaths between Rhodiola-supplemented and control flies, Rhodiola-fed flies exhibited decelerated aging. Although the observed extension in lifespan was associated with statistically insignificant reductions in fecundity, correcting for a possible dietary restriction effect still did not eliminate the difference between supplemented and control flies, nor does the effect of Rhodiola depend on dietary manipulation, strongly suggesting that Rhodiola is not a mere dietary restriction mimetic. Although this study does not reveal the causal mechanism behind the effect of Rhodiola, it does suggest that the supplement is worthy of continued investigation, unlike the other Chinese herbals, Lu Duo Wei (LDW), Bu Zhong Yi Qi Tang (BZYQT), San Zhi Pian (SZP, Three Imperial Mushrooms), Hong Jing Tian (Rhodiola) that were evaluated in this study.

DAF-2/Insulin-Like Signaling in C. elegans Modifies Effects of Dietary Restriction and Nutrient Stress on Aging, Stress and Growth

BackgroundDietary 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.Principal FindingsWe 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.ConclusionsThese 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.

Dietary restriction by bacterial deprivation increases life span in wild-derived nematodes

Dietary restriction is known to promote longevity in a variety of eukaryotic organisms. Most studies of dietary restriction have been performed on animals bred for many generations under conditions that differ substantially from their natural environment, raising the possibility that some apparent beneficial effects of dietary restriction are due to adaptation to laboratory conditions. To address this question in an invertebrate model, we determined the effect of dietary restriction by bacterial deprivation on life span in five different wild-derived Caenorhabditis elegans strains and two strains of the related species Caenorhabditis remanei. Longevity was enhanced in each of the wild-derived C. elegans strains, in most cases to a degree similar to that observed in N2, the standard laboratory strain. Both strains of C. remanei were substantially longer lived any of the C. elegans isolates, produced larger brood sizes, and retained the ability to produce offspring for a longer period of time. Dietary restriction failed to increase mean life span in one C. remanei isolate, but significantly increased the maximum life span of both C. remanei strains. Thus, we find no evidence that adaptation to laboratory conditions has significantly altered the aging process in C. elegans under either standard or food-restricted conditions.

Dietary Restriction Enhances Kainate-Induced Increase in NCAM While Blocking the Glial Activation in Adult Rat Brain

In the present study effect of dietary restriction (DR) on neuronal plasticity markers neural cell adhesion molecule (NCAM) and its polysialylated form PSA-NCAM and astrocytic marker glial fibrillary acidic protein (GFAP) was assessed following brain injury by intraperitoneal injection of kainic acid or physiological saline in adult male wistar rats. After 7-day recovery period, rats were sacrificed to study the NCAM-ir, PSA-NCAM-ir, and GFAP-ir in all the groups with immunohistofluorescence and immunoblotting. We noticed increase in NCAM and PSA-NCAM expression after KA excitotoxicity, and DR enhanced this increase in NCAM and PSA-NCAM expression. A marked increase in NCAM and PSA-NCAM-ir was observed in CA3 region of hippocampus, subgranular region and hilus of dentate gyrus, hypothalamus, and piriform cortex in both vehicle treated as well KA-treated DR rats as compared to vehicle and KA-treated AL rats, respectively. Whenever, CNS is damaged it undergoes an injury response called reactive gliosis. Our study confirmed the neuroprotective role of DR as evident from attenuation of GFAP-ir and enhanced levels of neuronal plasticity markers NCAM and PSA-NCAM. The potential beneficial role of DR regimen in attenuating KA-induced reactive astrogliosis and enhancing expression of neuronal plasticity markers may point the way to new strategies of intervention therapy by DR that will facilitate recovery from ageing and disease related neuronal dysfunction and enhance restorative processes by modulating astrogliosis.

Intermittent Dietary Restriction as a Practical Intervention in Aging

Recent studies on the effects of dietary restriction (DR) in rodents and primates have shown that even late-onset short-term regimens can bring about comparable beneficial changes seen in animals subjected to life-long DR. We examined the effect of 3 months of DR on the expression of antioxidant enzymes and antioxidants, heat-shock protein 70 (HSP-70), neural cell adhesion molecule (NCAM) and its polysialylated form, PSA-NCAM, as well as astrocytic marker glial fibrillary acidic protein (GFAP) in 18-month-old middle-aged rats. The present study shows that DR initiated in late adulthood confers beneficial effects, such as attenuation of oxidative stress, enhanced expression of HSP-70, neural plasticity markers NCAM, and PSA-NCAM, and reduced levels of GFAP.

Developmental stress impairs song complexity but not learning accuracy in non-domesticated zebra finches (Taeniopygia guttata)

Food restrictions early in life can have adverse effects on the development of adult avian song structure. Nutritional deficiencies during brain development are thought to impair the growth of neural circuits responsible for learning and production of song in adulthood. Thus, the quality of song may reflect the quality of the singer due to the costs associated with neural development early in life. Recent investigations have focused on domesticated laboratory strains of zebra finches where early dietary deficiencies have significantly reduced the complexity of song and its sexual attractiveness. Domesticated zebra finches may be more sensitive to the early effects of moderate under-nutrition on song complexity than their non-domesticated counterparts. In an aviary experiment with non-domesticated zebra finch stock, we found that song complexity when measured by a linear combination of six variables was reduced in food-restricted birds, with syllable rate and maximum syllable frequency as the principal variables affected. The restriction had no effect on learning accuracy when song phrases of experimental birds were compared to those of their fathers.This result demonstrates that early nutrition may differentially affect the development of neural processes that influence learning accuracy and song complexity. While the finding of negative effects of dietary restriction on song complexity is robust for zebra finches and is not an artefact of domestication, it does not explain why some nutritionally stressed populations of wild zebra finches have more complex songs than those from other regions of Australia characterised by greater food availability.