Effects Of Dietary Restriction Research Articles

Regulation of Lifespan in Drosophila by Modulation of Genes in the TOR Signaling Pathway

In many species, reducing nutrient intake without causing malnutrition extends lifespan [1–3]. Like DR (dietary restriction), modulation of genes in the insulin-signaling pathway, known to alter nutrient sensing, has been shown to extend lifespan in various species [1–4]. In Drosophila, the target of rapamycin (TOR) and the insulin pathways have emerged as major regulators of growth and size. Hence we examined the role of TOR pathway genes in regulating lifespan by using Drosophila. We show that inhibition of TOR signaling pathway by alteration of the expression of genes in this nutrient-sensing pathway, which is conserved from yeast to human, extends lifespan in a manner that may overlap with known effects of dietary restriction on longevity. In Drosophila, TSC1 and TSC2 (tuberous sclerosis complex genes 1 and 2) act together to inhibit TOR (target of rapamycin), which mediates a signaling pathway that couples amino acid availability to S6 kinase, translation initiation, and growth [5]. We find that overexpression of dTsc1, dTsc2, or dominant-negative forms of dTOR or dS6K all cause lifespan extension. Modulation of expression in the fat is sufficient for the lifespan-extension effects. The lifespan extensions are dependent on nutritional condition, suggesting a possible link between the TOR pathway and dietary restriction.

Lower body temperature as a potential mechanism of life extension in homeotherms

Although best known for his studies on the anti-aging effects of dietary restriction, Dr Roy Walford began his career by studying the anti-aging effects of lowering body temperature. As a tribute to his long and productive career, we review these pioneering studies and the singular influence these have had on our own thinking about the potential for lower body temperature to extend the life span of homeotherms. We show our results from a study of six classical inbred strains of mice that depict marked strain variation in the body temperature response to dietary restriction. In addition, we show a genome scan from a recombinant inbred strain panel in which we identified a significant quantitative trait locus on murine chromosome 9 and a provisional locus on chromosome 17 that specify variation in the response of body temperature to dietary restriction. These discoveries suggest that we can now extend the studies of Dr Walford to critically test whether lower body temperature can prolong the life span of mammals.

Ovarian and hormonal responses to a progesterone-releasing controlled internal drug releasing treatment in dietary-restricted goats

An experiment was conducted to evaluate the effects of dietary restriction on ovarian, endocrine (ovarian steroids and luteinizing hormone (LH) pulse) and metabolic (glucose, insulin and non-esterified fatty acid (NEFA)) profiles in goats treated with a progesterone-releasing controlled internal drug releasing (CIDR-G) device. Cycling goats were offered either a maintenance or a restricted (30% of requirement; n=4 per treatment) level of feeding. The dietary restriction was started on the day following ovulation. At 30–32 days after the start of food restriction, the goats received a prostaglandin F 2α (2 mg of dinoprost) injection followed by 10 days of CIDR-G treatment. Ovarian ultrasonographic images were monitored daily throughout the experiment and blood samples were collected daily just before the morning feeding for analysis of endocrine and metabolic profiles. Frequent blood samples (1 ml) were also collected at 10 min intervals for 8 h from −8 h to CIDR-G removal, and from 32 to 40 h after CIDR-G removal for analysis of LH pulses. Body weight was significantly ( P<0.05) decreased in the food-restricted animals. Oestrous behaviour and ovulation followed by a rise of plasma progesterone concentration were observed after the CIDR-G removal in all control animals but not in any of the food-restricted animals within 12 days after CIDR-G removal. The LH pulse frequency from 32 to 40 h after the CIDR-G removal was significantly ( P<0.05) lower in the food-restricted animals than in control animals (1.5±0.6 versus 3.8±0.5 pulses for 8 h). There was no significant difference in the glucose concentration in weekly plasma samples between control and food-restricted animals. Insulin concentrations from 2 weeks after the start of feed restriction were significantly ( P<0.05) lower in restricted animals than in control animals. The NEFA concentration in restricted animals was significantly ( P<0.05) increased after the start of feed restriction, and then decreased gradually to the basal level. The present results suggest that nutritionally induced anovulation after CIDR-G treatment is associated with a reduction in the frequency of LH pulses, and that insulin and NEFA, rather than the glucose concentration in the circulation, may be associated with the metabolic suppression of LH pulses.

Effects of Dietary Restriction and Metal Supplementation on the Accumulation of Iron-Laden Glial Inclusions in the Aging Rat Hippocampus

The mechanisms responsible for the pathological deposition of iron and other redox-active metals in the aging and degenerating mammalian CNS remain poorly understood. We previously demonstrated that normal aging and pharmacological (oxidative) stressors promote the transformation of astroglial mitochondria to iron-laden, diaminobenzidine (DAB)-positive cytoplasmic inclusions in sub-cortical regions of the rat brain. In the current study, we demonstrate that (1) numbers of DAB-positive glial granules in the rat dorsal hippocampus, an area implicated in learning and memory, progressively increase between 3, 12 and 22 months of age; (2) dietary restriction (40%), a manipulation that attenuates many mammalian aging processes, has no effect on the age-related accumulation of these gliosomes in the rat hippocampus; and (3) the latter can be accelerated by dietary supplementation of iron and copper. Our data support the view that dietary exposure to iron and/or copper in adult life can impact the sequestration of redox-active metals in aging hippocampal astroglia.

Aging increases DNase γ, an apoptosis-related endonuclease, in rat liver nuclei: effect of dietary restriction

Organ-specific endonuclease might play a role in the age-related increase in apoptosis in laboratory rodent tissues. In nuclear extracts from liver tissues of male F344 rats, the DNase activity gel system identified DNase γ, Ca2+/Mg2+-dependent endonuclease. The enzyme activity, which was measured at 3, 6, 16, and 24 months (mo) of age, was significantly increased between 16 and 24mo in control rats fed ad libitum (AL). The expression level of DNase γ-mRNA, estimated by a semi-quantitative reverse transcription-polymerase chain reaction method, was also increased at 24mo in group AL. The proportion of immunohistochemically DNase γ-positive cells, most of which were light-microscopically confined to apoptotic cells, was also significantly increased between 16 and 24mo. Dietary restriction, a powerful anti-aging intervention, which was achieved by providing 70% of the mean food intake in group AL from 6 weeks of age, inhibited the age-related increase in the enzyme activity and the proportion of immunostained cells; for the mRNA level, statistical significance was not obtained. The present study suggests that DNase γ is involved in an age-related increase in the apoptosis of rat liver, and that CR inhibits the increase as it minimized the age-related increase in the fraction of DNA-damaged hepatocytes susceptible to apoptosis.

Effects of dietary restriction on total body, femoral, and vertebral bone in SENCAR, C57BL/6, and DBA/2 mice

Dietary restriction (DR) increases the life span and retards aging, in part, by limiting free radical generation and oxidative damage. DR also reduces body mass, a major determinant of bone mass across the life span. We tested the hypothesis that DR has its most beneficial effects on bone in mouse strains with high free radical generation (sensitive to carcinogenesis [SENCAR] > C57 > DBA) versus the hypothesis that bone mass at weight-bearing sites is determined by body mass in DR and ad libitum (AL)-fed mice. Male mice of each strain were killed at 10 weeks of age (t 0) or randomized to an AL-fed or 30% DR feeding regimen for 6 months. Food consumption by AL-fed mice was measured daily, and DR mice received 70% of the amount of food consumed by their respective AL-fed mice the previous day. Body fat (%) and bone mineral density (BMD) and content (BMC) were determined by PIXImus densitometry. There were strain-dependent effects on body mass, crown-to-rump length, percent body fat, and total body, femoral, and vertebral BMD and BMC under all conditions. SENCAR mice were heavier, longer, had larger bones, and generally exhibited higher total body, femoral, and vertebral BMC and BMD than C57 and DBA mice. DR had beneficial effects on BMD and BMC in the vertebrae of the SENCAR mouse model of high free radical generation and in the obese, diabetes-prone C57 mouse model of high end-stage protein glycation. DR DBA and SENCAR mice had lower femoral BMDs and BMCs than their respective AL-fed controls. Regression analysis confirmed linear relationships between total and lean body mass and total body and femoral BMDs and BMCs, suggesting that physiologic adaptation to a lower body mass accounts for the lower femoral bone mineral values observed in DR versus AL-fed mice. Thus, both hypotheses are, at least, partially valid. DR is beneficial in the trabeculae-rich vertebrae of animal models of high oxidant stress, and total/lean body mass determines BMD and BMC in the weight-bearing femur in DR and AL-fed mice.

Selective alteration of DNA fragmentation and caspase activity in the spinal cord of aged rats and effect of dietary restriction

Age-related alterations in CNS may preferentially affect spinal cord. We report here that in spinal cord of aged (30-month-old) rats, a significant increase of DNA fragmentation accompanied by an increased activity of caspase-1, but not of caspase-3, can be measured. The increase in caspase-1 activation, but not the increased level of DNA fragmentation, was substantially reverted by long-lasting dietary restriction.

Gene-diet interactions in brain aging and neurodegenerative disorders.

While there are many examples of people who live for 100 years or more with little evidence of a decline in brain function, many others are not so fortunate and experience a neurodegenerative disorder, such as Alzheimer disease or Parkinson disease. Although an increasing number of genetic factors that may affect the risk for neurodegenerative disorders are being identified, emerging findings suggest that dietary factors play major roles in determining whether the brain ages successfully or experiences a neurodegenerative disorder. Dietary factors may interact with disease-causing or predisposing genes in molecular cascades that either promote or prevent the degeneration of neurons. Epidemiologic findings suggest that high-calorie diets and folic acid deficiency increase the risk for Alzheimer disease and Parkinson disease; studies of animal models of these disorders have shown that dietary restriction (reduced calorie intake or intermittent fasting) and dietary supplementation with folic acid can reduce neuronal damage and improve behavioral outcome. Animal studies have shown that the beneficial effects of dietary restriction on the brain result in part from increased production of neurotrophic factors and cytoprotective protein chaperones in neurons. By keeping homocysteine levels low, folic acid can protect cerebral vessels and prevent the accumulation of DNA damage in neurons caused by oxidative stress and facilitated by homocysteine. Although additional studies are required in humans, the emerging data suggest that high-calorie diets and elevated homocysteine levels may render the brain vulnerable to age-related neurodegenerative disorders, particularly in persons with a genetic predisposition to such disorders.

The effects of dietary restriction on humeral and mandibular bone in SENCAR, C57BL/6, and DBA/2 mice

Dietary restriction (DR) increases the life span and retards the development of age-related disorders. However, the low body mass that accompanies DR is associated with risk factors for fracture that may outweigh the beneficial effects of DR on cellular aging that are mediated, in part, by limiting free radical generation and oxidative damage. We tested the effects of DR in murine models that differ in free radical generation capacity (SENCAR > C57 > DBA). Male mice of each strain were killed at 10 weeks of age (t 0; time zero) or randomized to an ad libitum-fed (AL-fed) or 30% DR feeding regimen for 6 months. The food consumption of AL-fed mice was measured daily. DR mice received 70% of the amount of food consumed by their respective AL-fed mice the previous day. The DR diet was normalized with respect to calcium (Ca), phosphorus (P), and micronutrients. Lean body mass (LBM), bone mineral density (BMD), and bone mineral content (BMC) in the humerus and mandible were determined by PIXImus densitometry. The length and midshaft width of the humerus were determined by direct measurement. There were highly strain- and diet/time-dependent effects on LBM, humerus length, mandibular and humeral BMD, and humeral BMC. The interaction between diet/time and strain was more significant in the humerus than the mandible. All 30% DR mice had lower humeral BMDs and BMCs than their respective AL-fed controls. However, 30% DR C57 and DBA (but not SENCAR) mice had higher humeral BMD and BMC than their respective t 0 controls. There was a linear relationship between LBM and humeral BMD and BMC in both AL-fed and 30% DR mice, suggesting that the lower BMD and BMC in 30% DR mice, relative to AL-fed controls, reflects a physiologic adaptation to lower biomechanical loading. Mandibular BMC in 30% DR C57 (but not DBA or SENCAR) mice was lower than that observed in their AL-fed controls. Mandibular BMD and BMC increased versus t 0 values in 30% DR mice of all strains.

Insulin sensitivity and glucose effectiveness from three minimal models: effects of energy restriction and body fat in adult male rhesus monkeys.

The minimal model of glucose disappearance (MINMOD version 3; MM3) and both the one-compartment (1CMM) and the two-compartment (2CMM) minimal models were used to analyze stable isotope-labeled intravenous glucose tolerance test (IVGTT) data from year 10 of a study of the effect of dietary restriction (DR) in male rhesus monkeys. Adult monkeys were energy restricted (R; n = 12) on a semipurified diet to approximately 70% of control (C) intake (ad libitum-fed monkeys; n = 12). Under ketamine anesthesia, fasting insulin levels were greater among C monkeys. Insulin sensitivity estimates from all models were greater in R than C monkeys, whereas glucose effectiveness estimates were not consistently greater in R monkeys. Fasting plasma glucose as well as hepatic glucose production and clearance rates did not differ between groups. Body fat, in part, statistically mediated the effect of DR to enhance insulin sensitivity indexes. Precision of estimation and intermodel relationships among insulin sensitivity and glucose effectiveness estimates were in the ranges of those reported previously for humans and dogs, suggesting that the models may provide valid estimates for rhesus monkeys as well. The observed insulin sensitivity indexes from all models, elevated among R vs. C monkeys, may be explained, at least in part, by the difference in body fat content between these groups after chronic DR.

Dietary Restriction and Beta-Cell Sensitivity to Glucose in Adult Male Rhesus Monkeys

We examined the effects of dietary restriction (DR) and age on ss-cell function and peripheral insulin sensitivity in rhesus monkeys. A semipurified diet was provided either ad libitum for approximately 8 hours/day to controls (C) or as approximately 70% of baseline intake to restricted (R) animals for 10 years. The minimal model of C-peptide secretion and kinetics and the labeled 2-compartment minimal model of glucose kinetics were identified using plasma glucose, C-peptide, and insulin concentrations during an intravenous glucose tolerance test. R monkeys had less body fat, lower basal ss-cell sensitivity to glucose (Ø(b)), greater insulin sensitivity, and lower first-phase plasma insulin response. DR did not significantly affect first-phase and second-phase ss-cell sensitivity to glucose. Indices of body fatness were highly predictive of the effect of DR on Ø(b), fasting insulin concentration and insulin responses to glucose. Enhanced peripheral insulin sensitivity among R monkeys was strongly correlated with lower Ø(b).

Gallbladder motility in obesity, diabetes mellitus and coeliac disease.

We reviewed data on gallbladder motility in obesity, diabetes and coeliac disease. In obesity, a condition characterised by increased risk of gallstone(s), decreased gallbladder motility has heterogeneously been reported as a consequence of the different type of meals used to induce gallbladder contraction, characteristics of the population studied, technique used, and proportion of patients with hyperinsulinaemia. Moreover, recent studies have evaluated the effect of dietary restriction on gallbladder motility in obese patients. A two- to three-fold increase in the risk of cholesterol gallstone(s) has been reported in diabetic patients, mainly in relation to obesity and hypertriglyceridaemia. Furthermore, decreased gallbladder motility has been described and attributed to other factors, including underlying autonomic neuropathy, reduced gallbladder sensitivity to cholecystokinin and/or reduced number of cholecystokinin receptors on the gallbladder wall. Impaired gallbladder motility has been reported also in patients with coeliac disease in relation to reduced secretion of enteric hormones and/or decreased gallbladder sensitivity to them. In particular, untreated coeliacs, when compared to controls, showed low postprandial cholecystokinin and increased fasting somatostatin levels. Interestingly, the correlation between fasting somatostatin levels and gallbladder size has clearly been confirmed in patients affected by somatostatinoma or treated with somatostatin or its analogues. Gallbladder motility can be affected by various clinical conditions, such as obesity, diabetes mellitus and coeliac disease.

RESTRICTED FEEDING AND BONE MASS IN AN ANIMAL MODEL OF THE FEMALE ATHLETE TRIAD

Previous work in this laboratory demonstrated that female rats, restricted-fed to persistent anestrus and allowed unlimited access to running wheels, had significantly lower total body and femoral BMC and BMD compared to ad libitum-fed rats. Also, and libitum-fed rats, with unlimited access to running wheels, had significantly greater total body and femoral BMD and BMC compared to sedentary rats. PURPOSE To examine the effects of dietary restriction and exercise on bone mass in female rats. METHODS Twenty-two female Sprague-Dawley rats (age 40 days) were randomly assigned to four groups: ad libitum-fed running, ad libitum-fed sedentary, restricted-fed running, and restricted-fed sedentary. Running rats were individually housed with digitally monitored running wheels. Rats were fed pelleted AIN-G chow. Beginning at 159 days, the restricted-fed rats were subjected to 30% dietary restriction to initiate weight loss and anestrus. After 60+ days in anestrus (day 280), total body and femoral BMD and BMC were measured by dual-energy x-ray absorptiometry. Separate ANOVAs were used to examine the effects of feeding and exercise on BMD and BMC. RESULTS There were significant main effects (p < 0.05) for feeding and exercise on body mass such that ad libitum-fed and running rats had significantly greater body mass compared to restricted-fed and sedentary rats. Prior to normalizing for body mass, restricted-fed and sedentary rats had significantly less femoral BMD than ad libitum-fed and running rats. However, when normalized for body mass, restricted-fed and sedentary rats had significantly greater femoral BMD and BMC compared to ad libitum-fed and running rats. Feeding and exercise explained 65–85% and 21–56% of the variability in bone mass, respectively. CONCLUSION These findings suggest that the bone loss observed in the restricted-fed rats may have been due primarily to weight loss rather than anestrus.

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

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 C57BL6 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.

Therapeutic effects of restricted diet and exeicise is of benefit to patients with non-alcoholic steatohepatitis (NASH)

Therapeutic effects of restricted diet and exeicise is of benefit to patients with non-alcoholic steatohepatitis (NASH)

The Effects of Feeding Restriction on Metallothionein Levels and Ethoxyresorufin-O-Deethylase Activities in Mummichogs

Pollution exposure is thought to affect animals through increased maintenance costs, which lead to a decrease in the energy available for other production processes. This can cause weight loss in animals that are chronically exposed to sublethal pollution levels. Starvation and food deprivation have been shown to affect the expression of commonly used bioindicators in fish. The experiments reported in this article were designed to examine the effect of dietary restrictions (in the absence of pollution exposure) on metallothionein and ethoxyresorufin-O-deethylase (EROD; an indicator of CYP1A1 expression) levels in mummichogs Fundulus heteroclitus, a fish that has been extensively examined as an environmental bio-indicator species. Dietary restriction over a 35-d period led to weight loss and alterations in physiological indicators (condition index, liver glycogen, and RNA–DNA ratio) consistent with a reduction in available food. Liver EROD activity increased up to 20-fold on a gram basis and 7-fold on a total-liver basis after 35 d of food restriction. The induction of EROD activity was dependent on the level of caloric restriction. Metallothionein levels initially decreased but then increased slightly to near baseline levels after 35 d of dietary restriction. These results are discussed in the context of using mummichogs as bioindicators of pollution exposure.

Minimal effects of dietary restriction on neuroendocrine carcinogenesis in Rb+/- mice.

The efficacy of dietary restriction in retarding tumor growth is well established in rodents. However, gene and cell lineage specificity of dietary restriction effects is far less defined. Mice with a single copy of the retinoblastoma susceptibility gene (Rb) develop a well-established syndrome of mouse neuroendocrine neoplasia associated with Rb deficiency. Thus, if DR represses tumor growth in this model, it should be unambiguously attributed to the Rb defect in neuroendocrine cell lineages. To address this possibility, Rb(+/-) mice were entered into a diet restriction study. Surprisingly, 40-50% reductions in dietary intake, relative to an ad libitum group, started on either postnatal day 28 or 42 had little to no effect on either the frequency or growth of pituitary tumors either during the latency period (postnatal day 224) or at the time of their natural death. Consistent with cross-section data, survival of 65 diet restricted Rb(+/-) mice was almost identical to that of 67 Rb(+/-) mice fed ad libitum (AL); median life span was 414 and 436 days for AL and DR groups, respectively. These findings indicate that diet restriction provides no significant benefit in delaying growth and progression of neuroendocrine tumors exhibiting loss of RB function. They also introduce the possibility that RB is required for the tumor-repressive effects of DR.

Maternal protein restriction before pregnancy affects vital organs of offspring in Wistar rats

Epidemiologic studies indicate that undernutrition during fetal growth can have long-term effects on adult health. However, it is not known whether these effects are also associated with maternal undernutrition before conception. The objective of the present study was to examine the effect of dietary restriction before pregnancy on the vital organs and blood parameters of offspring at different time points. Wistar female rats in the restricted group were fed a diet consisting of 80 g protein/kg for 8 weeks before pregnancy and switched to 160 g protein/kg (control) from day 0 of pregnancy, while animals from the control group were fed 160 g protein/kg throughout life. The progeny were studied at birth (n = 71), at 94 days (n = 20), and at 180 days (n = 16). Weight gain during pregnancy was significantly lower (P <.01) for dams in the restricted group. At birth, relative weight for brain was lower (P ≤.008), while for kidney it was higher (P ≤.008) in the restricted group compared to control. At 94 days, the relative weights of brain, liver, and heart were lower (P ≤.01 for all) in the restricted group than in the control group. However, at 180 days, only liver and kidney showed lower (P ≤.01 for both) relative weights. Further, in the restricted group, increases in blood glucose at 94 days and in cholesterol at 180 days were significant (P <.01 for both) in the offspring. The results thus indicate that maternal undernutrition before conception not only affected growth of vital organs, but also resulted in increased levels of glucose and cholesterol in the offspring at adulthood. Copyright 2003, Elsevier Science (USA). All rights reserved.

Influence of Age at Weaning on Caecal Content Characteristics and Post-weaning Performance and Health of Rabbits

This study chiefly aimed to ascertain the effect of age at weaning on caecal content characteristics, post-weaning performance and health of rabbits. A secondary aim was to study the effect of dietary restriction on performance and health of rabbits. After delivery, 30 litters of 8 pups each, were housed in separate cages. Fifteen litters were weaned 24 days from birth (group W 24) while the other 15 were weaned at 28 days (group W28). After weaning, 53 rabbits of group W24 and 56 of group W28 were fed ad libitum (group LIB), while 53 rabbits of group W24 and 57 of group W28 were restricted (group RES). All the rabbits were kept in individual cages. Fourteen other rabbits of groups W24 (7 fed ad libitum and 7 restricted) and 7 of group W28 were sacrificed to obtain data regarding caecum weight and caecal content. Age at weaning affected neither the state of health nor the final live weight. In comparison with those of group W28, the rabbits weaned at 24 days had a lower daily gain until 35 days of age but gain was higher subsequently. From the 28th day, however, the feed intake and the feed conversion ratio of the group W24 rabbits were always better than those of W28. The restricted diet until 42 days resulted in a lower weight both at 42 days (1,078 vs. 1,164 g) and at 70 days (2,192 vs. 2,294 g). Indeed, from the 42nd day, despite receiving feed ad libitum the rabbits of the restricted group continued to ingest less feed (120.8 vs. 127.2 g) than those of the ad libitum group, and had a slightly lower daily gain (39.8 vs. 40.3 g). The measurements carried out on the caecum highlighted significant differences among the groups in caecal content (33.1 vs. 31.7 vs. 25.3 g respectively for groups W24LIB, W28 and W24RES), for total volatile fatty acids (53.2 vs. 50.6 vs. 44.5 mmol/l respectively for groups W24LIB, W28 and W24RES) for ammonia (7.0 vs. 7.2vs 8.8 mmol/l respectively for groups W24LIB, W28 and W24RES), for propionate (5.7 vs. 6.3 vs. 8.1% respectively for groups W24LIB, W28 and W24RES) and for propionate/butyrate (0.33 vs. 0.36 vs. 0.49 respectively for groups W24LIB, W28 and W24RES). (Asian-Aust. J. Anim. Sci. 2003. Vol 16, No. 10 : 1540-1544)

4P-1042 Inhibitory effect of dietary restriction on endothelial nitric oxide synthase expression and function

4P-1042 Inhibitory effect of dietary restriction on endothelial nitric oxide synthase expression and function