Simin Meydani
Tufts University, Immunology, Faculty Member
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Abstract The relationship between aging, nutrition and immunity is explored. Section headings include: Changes in nutritional status with aging; Effects of nutrients on immunity with aging; Protein and calories; Lipids; Vitamin B6;... more
Abstract The relationship between aging, nutrition and immunity is explored. Section headings include: Changes in nutritional status with aging; Effects of nutrients on immunity with aging; Protein and calories; Lipids; Vitamin B6; Ascorbic acid; Vitamin E; β-Carotene; ...
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Aging is associated with changes in immune response. I Decline in immunological vigor may contribute to many age-associated diseases such as cancer. Well-documented, age-related functional changes have been defined for both humoral and... more
Aging is associated with changes in immune response. I Decline in immunological vigor may contribute to many age-associated diseases such as cancer. Well-documented, age-related functional changes have been defined for both humoral and cell-mediated responses.v " Although all four major cell types of the immune system show age-related changes, the major alterations have been demonstrated in the T cells.":" In vitro. T cell-mediated functions such as antigen and mitogen-stimulated lymphocyte proliferation and IL-2 production have been shown to be decreased with age. Several groups have shown that the decrease in IL-2 production with age contributes to T cell-mediated defects observed with aging in rodents and humans.I"? Furthermore, IL-2 reconstitution in vitro and in vivo was shown to improve cell-mediated lymphocyte responses of aged mice. 8 ,9
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... Kent J. DeZee, MD, MPH. William Shimeall, MD, MPH. Kevin Douglas, MD. Jeffrey L. Jackson, MD, MPH. Walter Reed Army Medical Center; Washington, DC 20307. ... Joseph E. Baggott. Ann Intern Med July 19, 2005 143:155-156. ...
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Fifth AACR International Conference on Frontiers in Cancer Prevention Research, Nov 12-15, 2006 A223 Polyunsaturated fatty acid metabolites are known to be involved in inflammation, and fatty acid precursors and metabolites may also exert... more
Fifth AACR International Conference on Frontiers in Cancer Prevention Research, Nov 12-15, 2006 A223 Polyunsaturated fatty acid metabolites are known to be involved in inflammation, and fatty acid precursors and metabolites may also exert genomic control over the expression of genes involved in proliferation and differentiation. Some researchers suggest that a higher ratio of omega-3/omega-6 fatty acids would be beneficial in cancer prevention and therapy, either alone or as an adjuvant to traditional treatments. In this study, we examined whether dietary supplementation with fish oil (with a high omega-3/omego-6 ratio) or corn oil (with a low omega-3/omega-6 ratio) could influence lung carcinogenesis in the NNK carcinogen-induced mouse model of lung cancer. A/J mice (n=14/group) were fed AIN-93M semi-purified rodent diet alone or supplemented with menhaden fish oil (10% wt/wt), corn oil (10% wt/wt), or soybean oil (10% wt/wt, as an isocaloric control) for three weeks prior to a single dose carcinogen injection (100 mg NNK/kg body weight), and 17 weeks thereafter. We found that dietary supplementation with 10% menhaden fish oil was able to decrease lung tumor multiplicity by 78%, compared to a control group receiving soybean oil supplementation (80% decrease vs. NNK injection alone). Corn oil supplementation had no effect on tumor incidence or tumor multiplicity. The mechanism behind these chemopreventive effects remains elusive, but does not seem to involve modulation of the nuclear hormone receptors RXRα, RARβ, or PPARγ; the cyclin dependent kinase inhibitor p21; the inducible enzyme cyclooxygenase-2; nor modulation of the mitogen IGF-I or its binding protein IGFBP-3 in total lung tissue. Ongoing research aims to determine molecular changes occurring at tumor initiation sites and molecular mechanisms of action at the cellular level.
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Concentration of prostaglandins E1, E2, F2alpha, and 15 keto, 13, 14-dihydro F2alpha (MPF2alpha), were measured in gastric, duodenal, jejunal, and ileal mucosa, and in the luminal contents of these gastrointestinal segments in miniature... more
Concentration of prostaglandins E1, E2, F2alpha, and 15 keto, 13, 14-dihydro F2alpha (MPF2alpha), were measured in gastric, duodenal, jejunal, and ileal mucosa, and in the luminal contents of these gastrointestinal segments in miniature swine at 30, 60, and 120 min after they ingested a liquid nutrient meal. Large quantities of E1 and F2alpha were present in gastric contents at 30 min with lesser amounts of E2 and MPF2alpha. The concentrations of E1, E2, and F2alpha in the gastric contents decreased progressively with time after feeding. The total quantity and the concentrations of E1 and F2alpha decreased with passage of ingesta through the duodenum and jejunum. Mucosal concentrations of E1 and F2alpha were greatest in the duodenum and proximal jejunum and lowest in gastric mucosa. These results indicate that there is considerable production and metabolism of prostaglandins in the gastrointestinal tract, with major amounts secreted into the luminal contents of the stomach and duodenum after food intake.
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Research Interests: Incidence Geometry, Medicine, Antioxidants, Humans, Internal Medicine, and 15 morePlacebo, Nursing Homes, Female, Male, Dietary Supplements, Incidence, Common Cold, Nutritional Status, Aged, Middle Aged, Respiratory Tract Infection, JAMA, Homes for the Aged, Relative Risk, and Medical and Health Sciences
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ABSTRACT The in vitro and in vivo immune response was investigated in adult squirrel and cebus monkeys fed corn oil (CORN) or coconut oil (COCO) diets (31% calories as fat) since birth. The in vitro blastogenic response of lymphocytes... more
ABSTRACT The in vitro and in vivo immune response was investigated in adult squirrel and cebus monkeys fed corn oil (CORN) or coconut oil (COCO) diets (31% calories as fat) since birth. The in vitro blastogenic response of lymphocytes cultured in calf serum or in autologous serum to T- and B-cell mitogens was compared between the two species fed the two types of fat. For in vivo measurements of immune competence, all monkeys received measles vaccine and their serum antibody titers were measured by hemagglutination inhibition assay along with measurement of IgG, IgM and IgA. Prostaglandin E2 synthesis by peripheral blood mononuclear cells (PBMC) was measured following stimulation with calcium ionophore. Cells cultured in either calf or autologous serum responded in the same relative fashion to mitogens. However, culturing cells in autologous serum exaggerated the dietary differences found. Cebus monkey lymphocytes were more responsive than squirrel monkeys, but squirrel monkeys fed corn oil had the lowest blastogenic responses to T-cell and B-cell mitogens and lower antibody titers to measles vaccine. Cebus monkey PBMC also generated less PGE2 than those from squirrel monkeys. The data suggest that genetic variation in phospholipid metabolism, possibly including PGE2 synthesis, may underlie differences in the immune response to dietary fat unsaturation by these two species of monkeys.
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Santoguin and vitamin E were added to the diets of six week old CBA/J mice that were fed mouse chow and received daily subcutaneous casein (CAS) injections and 24 month old C57BL/6Nia mice fed a casein enriched diet respectively. DNA... more
Santoguin and vitamin E were added to the diets of six week old CBA/J mice that were fed mouse chow and received daily subcutaneous casein (CAS) injections and 24 month old C57BL/6Nia mice fed a casein enriched diet respectively. DNA synthetic responses to Phytohemagglutinin (PHA) and Concanavalin A (ConA) were measured in spleen cell cultures to determine the effects of these potent antioxidants on cellular immune function. The incidence and degree of amyloidosis was measured after Congo red staining of formalin fixed sections.
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Bacterially‐synthesized menaquinones (MKn) may contribute to vitamin K (VK) nutriture. There are limited data on interindividual variability in endogenous MK synthesis and its relation to circulating forms of VK. Serum and fecal VK... more
Bacterially‐synthesized menaquinones (MKn) may contribute to vitamin K (VK) nutriture. There are limited data on interindividual variability in endogenous MK synthesis and its relation to circulating forms of VK. Serum and fecal VK concentrations were assessed in 13 healthy adults (45–65 yr) consuming a standardized diet for 14 d. Phylloquinone (PK), MK4 and MK6‐MK13 concentrations were measured by HPLC in fasting serum collected on day 8 and 72 hr‐fecal homogenates collected days 8–10. LC/MS was used to confirm individual MKn. PK, the primary dietary form, comprised only 6 ± 3% of total fecal VK content (fecal PK [mean ± SD]; 0.45 ± 0.17 μg/g dry wt), and was not correlated with serum PK concentrations (1.85 ± 0.89 pmol/L). No MKn were detected in serum. MK4 and MK6‐MK12 were detected in all, and MK13 in 7 fecal homogenates. Mean fecal MKn concentrations ranged from 0.17 ± 0.05 μg/g dry wt for MK4 to 4.95 ± 2.30 μg/g dry wt for MK10, with MK10 comprising 63 ± 19% of total fecal MKn...
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since the 1950s. Soc Hist Med 2001;14:79–106. 6. Lissau I, Overpeck MD, Ruan WJ, Due P, Holstein BE, Hediger ML. Body mass index and overweight in adolescents in 13 European countries, Israel, and the United States. Arch Pediatr Adolesc... more
since the 1950s. Soc Hist Med 2001;14:79–106. 6. Lissau I, Overpeck MD, Ruan WJ, Due P, Holstein BE, Hediger ML. Body mass index and overweight in adolescents in 13 European countries, Israel, and the United States. Arch Pediatr Adolesc Med 2004;158:27–33. 7. Zhou SS, Li D, Zhou YM, Sun WP, Liu QG. B-vitamin consumption and the prevalence of diabetes and obesity among the US adults: population based ecological study. BMC Public Health 2010;10:746. 8. Ahluwalia N, Dalmasso P, Rasmussen M, Lipsky L, Currie C, Haug E, Kelly C, Damsgaard MT, Due P, Tabak I, et al. Trends in overweight prevalence among 11-, 13and 15-year-olds in 25 countries in Europe, Canada and USA from 2002 to 2010. Eur J Public Health 2015;25(Suppl 2):28–32. 9. Althausen TL, Eiler JJ, Stockholm M. The effect of B vitamins on intestinal absorption and food utilization: metabolism studies in rats on diets deficient in certain B vitamins and during recovery from such diets. Gastroenterology 1946;7:555–61. 10. Milman N, Byg KE, Ovesen L, Kirchhoff M, Jurgensen KS. Iron status in Danish women, 1984-1994: a cohort comparison of changes in iron stores and the prevalence of iron deficiency and iron overload. Eur J Haematol 2003;71:51–61.
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Free radicals and reactive oxygen species (ROS) which are generated continuously cause mutagenic alterations resulting in cancer, aging and abnormalities in the nervous system. Accumulating evidence indicates that Vitamin E, the most... more
Free radicals and reactive oxygen species (ROS) which are generated continuously cause mutagenic alterations resulting in cancer, aging and abnormalities in the nervous system. Accumulating evidence indicates that Vitamin E, the most potent lipid peroxyl radical scavenger, may reduce free radical induced chromosomal damages through inhibition of free radical formation, and activation of endonuclease that can be triggered by intracellular oxidative stress, and by increasing the rate of removal of damaged DNA. Although some studies suggest a potential usefulness of Vitamin E in the prevention of mutagenic effects caused by genotoxic free radicals, other studies report no effects. Thus the data are not conclusive enough to be used as a basis to change the current recommended dietary allowances (RDA). Future research should address molecular mechanisms underlying the protective effects of Vitamin E and develop appropriate biologically relevant biomarkers of DNA damage to further help in determining the dietary levels of Vitamin E needed to protect the genetic pool from internally and externally induced DNA damages. © 2001 Elsevier Science B.V. All rights reserved.
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Aging is associated with significant changes in the immune system, a phenomenon called immunosenescence, which has been implicated in the increased morbidity of, and mortality from, infection in the elderly. While many immune functions... more
Aging is associated with significant changes in the immune system, a phenomenon called immunosenescence, which has been implicated in the increased morbidity of, and mortality from, infection in the elderly. While many immune functions are affected by aging, the defects in T cells are the most pronounced and best characterized. Nutritional intervention has been proposed to be helpful in delaying or reversing immunosenescence, which is well exemplified in the case of vitamin E. Studies in several species of animals show that vitamin E deficiency impairs immune function, which can be corrected by vitamin E repletion. Although vitamin E deficiency is rare in humans, increased intake above recommended levels has been shown to enhance T cell function, particularly in aged animals and humans. The mechanisms for this effect of vitamin E involve both a direct effect of enhancing T cell activation and effector function and a suppressing effect on production of prostaglandin E2, a T cell-suppressing lipid mediator known to increase with aging. Vitamin E-induced enhancement of immune functions has significant clinical implications as evidenced by the findings that vitamin E supplementation is associated with increased resistance to respiratory infections in both aged mice and older adults. In this chapter, we review age-related changes in the immune system, evidence for an immunomodulating effect of vitamin E, the underlying mechanisms, and its clinical application in protecting the host against infection in both animal models and humans.
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Macrophages (Mphi) from old mice produce more PGE2 than those from young mice, contributing to the dysregulation of the immune and inflammatory responses with age. This study was conducted to determine the mechanisms of the age-associated... more
Macrophages (Mphi) from old mice produce more PGE2 than those from young mice, contributing to the dysregulation of the immune and inflammatory responses with age. This study was conducted to determine the mechanisms of the age-associated increase in Mphi PGE2 production. PGE2 production is influenced by the availability of the substrate arachidonic acid and by activity of the enzyme cyclooxygenase (Cox). We demonstrate that when the substrate is not the limiting factor, Mphi from old mice have significantly higher LPS-stimulated Cox activity than young mice, indicating that the age-associated increase in PGE2 production is due to increased enzyme activity and not to changes in substrate level. Cox activity is determined by the enzyme level and requires hydroperoxide for activation. Of the two Cox isoforms, Cox 1 is constitutively expressed in nearly all cells; whereas Cox 2 is induced by a wide range of ligands. Analysis of accumulated and de novo synthesis of constitutive Cox 1 an...
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Recent studies have suggested that obesity may be associated with impaired immune function as well as the related reduction in resistance to infection. The most commonly utilized animal model for d...
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Zinc is essential for the regulation of immune response. T cell function declines with age. Zinc supplementation has the potential to improve the serum zinc concentrations and immunity of nursing home elderly with a low serum zinc... more
Zinc is essential for the regulation of immune response. T cell function declines with age. Zinc supplementation has the potential to improve the serum zinc concentrations and immunity of nursing home elderly with a low serum zinc concentration. We aimed to determine the effect of supplementation with 30 mg Zn/d for 3 mo on serum zinc concentrations of zinc-deficient nursing home elderly. This was a randomized, double-blind, placebo-controlled study. Of 53 nursing home elderly (aged ≥65 y) who met eligibility criteria, 58% had a low serum zinc concentration (serum zinc <70 μg/dL); these 31 were randomly assigned to zinc (30 mg Zn/d) (n = 16) or placebo (5 mg Zn/d) (n = 15) groups. The primary outcome measure was change in serum zinc concentrations between baseline and month 3. We also explored the effects of supplementation on immune response. Baseline characteristics were similar in the 2 groups. The difference in the mean change in serum zinc was significantly higher, by 16%, i...