Faculty and Research
Faculty by Name
Bruce N. Ames
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Bruce N. Ames
Professor of the Graduate School Division of Biochemistry and Molecular Biology
Research Interests
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A. Lipoic acid and acetyl-carnitine supplements ameliorate the mitochondrial decay of aging. A series of papers (317;338;347;358; 379;385;394;398;405;408;409;415;416;433;454;455;456;490; 519) have shown that: 1) Mitochondrial decay is likely to be a major contributor to aging (317;338;347;358;379;484). 2) Four areas of mitochondrial metabolism decline with age (379;398;405): (a) oxidant by-products increase with a concomitant increase in ascorbate, protein, lipid, and nucleic acid oxidation; (b) cardiolipin decreases in mitochondrial membranes; (c) membrane potential decreases; and (d) oxygen utilization decreases. 3) Acetyl carnitine, a mitochondrial transporter for fatty acids, when fed to old rats for several weeks (408;490), reverses three aspects of mitochondrial decay (see items 2)(b),(c),(d) above); lipoic acid, a mitochondrial coenzyme, when fed to old rats for a several weeks (405;409;416;433) reverses the increase in oxidant by-products (item 2a above); and the combination of acetyl carnitine and lipoic acid, when fed to old rats improves mitochondrial function in the liver and brain and increases activity levels and scores on cognition tests (454;455;456). Recent studies on dogs show that the combination also improves cognition in old beagle dogs (464;519). A recent double blind clinical trial on aged humans from Dr. Vita’s laboratory shows a decrease in hypertension (515a). Supported by extensive preliminary results showing that the combination lowers C-reactive protein in sickle cell disease, a clinical trial on the combination was recently funded (Lal & Ames R21) to test the effect of the combination on inflammation accompanying sickle cell disease. Lipoic acid has also been shown to protect retinal pigment epithelial cells from oxidation, a model for macular degeneration (499;511).
B. Micronutrient shortage accelerates the degenerative diseases of aging: triage. A new theory (510) about homeostasis during micronutrient shortage, if confirmed, will radically change thinking about requirements for micronutrients and public health. The triage hypothesis posits that the risk of degenerative diseases associated with aging, including cancer, cognitive decline, and immune dysfunction, can be decreased by ensuring adequate intake of micronutrients (the 40 essential vitamins, minerals, amino acids, and fatty acids) earlier in life, a simple and inexpensive solution to a very large public health problem (510). It is hypothesized that during evolution one homeostatic mechanism that developed during shortage of any micronutrient involves protein triage, such that metabolism essential for short term survival is maintained at the expense of metabolism that only impacts years later. A possible mechanism is that enzymes required for short-term survival have tighter binding constants for micronutrient cofactors than enzymes involved in functions whose loss has less immediate adverse impacts. The theory explains many of his observations and much in the published literature (510). For example the theory predicts that short-term metabolism likely to be affected includes some types of DNA damage (444; 463; 468; 479; 482; 510; 512) and mitochondrial leakage of oxidants (427; 451; 504; 510; 512; 514), both of which increase with age. Similarly, the 6 aspects of adaptive immune dysfunction that increase with age, including CD8 loss (491), would be expected to be more vulnerable to micronutrient scarcity than innate immunity that stands in readiness to defend against more immediate invasions. More recent unpublished analyses suggest that all 6 aspects of adaptive immune system aging are increased by those micronutrient deficiencies so far examined. A corollary of the triage hypothesis is that micronutrient deficiencies would accelerate late-onset diseases causally linked to these earlier sub-clinical insults, including cancer, cognitive decline, and vulnerability to infection. Thus, the triage hypothesis predicts a rebalancing of metabolism during micronutrient shortage that eventually results in late-onset disease, but has insidious, but detectable, immediate effects in areas of metabolism not essential for short-term survival. Micronutrient intakes less than the Estimated Average Requirement (EAR), i.e. > 2 standard deviations below the Recommended Dietary Allowance (RDA), are considered to be inadequate, and by this definition inadequacy is unusually widespread in the US population, especially in the poor, children, adolescents, the obese, and the elderly. A number of these micronutrient inadequacies affect more than half the U.S. population (e.g. for Mg, 56% of the U.S. population is <EAR (510); for vitamin D, African-Americans as a group are <EAR (510; 528). Societal concern is low because no overt pathology has been associated with these levels of deficiency. The triage hypothesis predicts that insidious changes may indeed be occurring, providing a unifying rationale for diverse observations in the literature that suggest links between micronutrient availability, aging, and the diseases of aging, many of these observations are discussed, though not the immune system, in the recent triage paper (510).
C. Magnesium Deficiency Accelerates Cellular Senescence (531). Magnesium inadequacy affects over half of the US population and is associated with increased risk for many age-related diseases, yet the underlying mechanisms are unknown. Altered cellular physiology has been demonstrated after acute exposure to severe magnesium deficiency, but few reports have addressed the consequences of long-term exposure to moderate magnesium deficiency in human cells. Therefore, IMR-90 human fibroblasts were continuously cultured in magnesium-deficient conditions to determine the long-term effects on the cells. These fibroblasts did not demonstrate differences in cellular viability or plating efficiency, but did exhibit a decreased replicative lifespan in populations cultured in magnesium-deficient compared to standard media conditions, both at ambient (20% O2) and physiological (5% O2) oxygen tension. The growth rates for immortalized IMR-90 fibroblasts were not affected under the same conditions. IMR-90 fibroblast populations cultured in magnesium-deficient conditions had increased senescence-associated beta-galactosidase activity and increased p16INK4a and p21WAF1 protein expression compared to cultures from standard media conditions. Telomere attrition was also accelerated in cell populations from magnesium-deficient cultures. Thus, the long-term consequence of inadequate magnesium availability in human fibroblast cultures was accelerated cellular senescence, which may be a mechanism through which chronic magnesium inadequacy could promote or exacerbate age-related disease. A paper on increased mitochondrial DNA protein crosslinks on Mg deficiency is in preparation.
D. High dose B vitamins stimulate mutant enzymes with decreased binding for a coenzyme. A review (453) showed that about 50 human genetic diseases due to defective enzymes can be remedied or ameliorated by the administration of high doses of the vitamin component of the corresponding coenzyme, which at least partially restores enzyme activity. Up to a third of mutations in a gene result in the corresponding enzyme having a decreased binding constant (increased Km) for a coenzyme results in a lower rate of reaction. The review points out that many of the B vitamins, given at levels 10-100 times the RDA, can raise coenzyme activity levels by an order of magnitude or more. Several single-nucleotide polymorphisms (SNPs) in the literature with a deleterious phenotype under some conditions decrease binding constants and are thus also likely to be remediable by raising cellular concentrations of the cofactor by high dose vitamin therapy. This review raises the issue of whether some appreciable percentage of the population may require a higher level of a particular vitamin or substrate for optimum function.
E. High dose B vitamins and aging. A follow-up review (507), points out that it is common for proteins to become deformed with age, e.g. by membranes becoming stiffer, and that this raises the question whether high dose B vitamins may be useful in the elderly.
F. gamma-Tocopherol (γ-T) as an important form of Vitamin E. A series of papers (377;435;446; 459;465;466;473;492;493;518;525) calls attention to γ-T, a major form of vitamin E in the diet, which is not usually present in supplements, as a nutrient that deserves further attention. γ-T is in many plant seeds and in the US diet, but has drawn little attention compared with alpha-tocopherol (α-T), the predominant form of vitamin E in tissues and the primary form in supplements. Recent studies indicate that γ-T may also be important to human health and that it possesses unique features that distinguish it from α-T. γ-T is a powerful lipophilic nucleophile which, unlike α-T, traps the NOx released during inflammation as nitro-γ-T (377;465;466). γ-T is well absorbed from the diet and accumulates to a significant degree in some human tissues; it is metabolized largely to 2,7,8-trimethyl-2-( -carboxyethyl)-6-hydroxychroman (γ-CEHC), which is mainly excreted in the urine. γ-CEHC, but not the corresponding metabolite derived from α-T, has natriuretic activity that may be of physiologic importance. Both γ-T and γ-CEHC, but not α-T, inhibit cyclooxygenase activity (435;473) and, thus, possess antiinflammatory properties. Some human and animal studies indicate that plasma concentrations of γ-T are inversely correlated with the incidence of cardiovascular disease and prostate cancer. These distinguishing features of γ-T and its metabolite suggest that γ-T may contribute significantly to human health in ways not recognized previously. This possibility should be further evaluated, especially considering that high doses of α-T deplete plasma and tissue γ-T, in contrast with supplementation with γ-T, which increases both. A review covers current information on the bioavailability, metabolism, chemistry, and nonantioxidant activities of γ-T, as well as epidemiologic data concerning the relation between γ-T and cardiovascular disease and cancer. Other work (492; 493) showed that γ-T, unlike α-T, is a powerful inhibitor of prostate cancer cells, compared to normal cells through interrupting sphingolipid synthesis. In the first two of a series of papers in preparation (518; 525) that use human cells in culture, rats, and human clinical trials, γ-T is shown to be clinically promising as an anti-inflammatory drug for asthma.
G. Micronutrient deficiencies and brain development. A series of thorough critical reviews have been published on evidence relevant to a possible causal relationship between a micronutrient deficiency [Vitamin D (522), iron (514), choline (508), DHA/omega-3 fatty acids (498; 509; 516; 520)] and adverse cognitive or behavioral effects during brain development. These reviews have focused attention on the importance of adequate micronutrients for normal brain development. A major baby formula company decided to include DHA in all of its formulas following the review on DHA, though it is not known whether the review influenced the decision. The new work on vitamin D (528) is discussed below and should call attention to the widespread inadequacy of Vitamin D in certain populations living at high latitudes and its role in brain development. “This critical analysis of vitamin D function and the brain is a model of careful thinking about nutrition and behavior”, says Gerald Weissmann, MD, Editor-in-Chief of the FASEB Journal “One wishes that all studies of nutritional supplements or requirements were this thoughtful. Drs. McCann and Ames deftly show that while Vitamin D has an important role in the development and function of the brain, its exact effects on behavior remain unclear. Pointing to the need for further study, the authors argue for vitamin D supplementation in groups at risk.” The new review on vitamin D shows that mechanistic and biological evidence strongly suggests that calcitriol (the hormone derived from vitamin D) is involved in brain development and critical brain functions, e.g. the calcitriol receptor (VDR) and the terminal calcitriol activating enzyme are distributed throughout both the fetal and adult brain. Thus, vitamin D is likely to be important in brain development and functioning; though evidence for a deleterious effect of vitamin D inadequacy in humans on cognition or behavior is inadequate and difficult to obtain. Vitamin D supplementation is inexpensive and its use is already recommended for preventing rickets and fractures. Accumulating evidence indicates that vitamin D might also protect against some types of cancer and autoimmune diseases. Thus, the possible prevention of brain dysfunction might be an additional bonus in groups whose vitamin D status is exceptionally low including many nursing infants, the elderly, and African-Americans. Dark skin is selected for, and is protective in the tropics against the UV burning rays of the sun, just as white skin is selected in Northern (high) latitudes for trapping as much UV as possible (about 6 times as efficient as dark skin) in order to make vitamin D. Thus, fair-skinned Northerners are at risk in Australia and Arizona from sunburns and UV-induced cancer and dark skinned people in the Northern US or Europe with little sun are at risk from rickets, bone fractures and probably some types of cancer. It remains to be seen if the levels of vitamin D in the population are sufficiently low to result in brain dysfunction.
H. Methylene blue. Methylene Blue (MB) and other diaminophenothiazines extend the life span of human IMR90 fibroblasts in tissue culture by >20 population doubling (PDLs) (527). MB has been used clinically for about a century to treat numerous ailments. MB delays senescence at nM levels in IMR90 by enhancing mitochondrial function. MB increases mitochondrial complex IV by 30%, enhances cellular oxygen consumption by 37–70%, increases heme synthesis, and reverses premature senescence caused by H2O2 or cadmium. MB also induces ~250 phase-2 antioxidant enzymes in hepG2 cells. Flavin-dependent enzymes are known to use NAD(P)H to reduce MB to leucomethylene blue (MBH2), whereas cytochrome c reoxidizes MBH2 to MB. Experiments on lysates from rat liver mitochondria suggest the ratio MB/cytochrome c is important for the protective actions of MB. It is proposed that the cellular senescence delay caused by MB is due to cycling between MB and MBH2 in mitochondria, which may partly explain the increase in specific mitochondrial activities. Cycling of MB between oxidized and reduced forms may block oxidant production by mitochondria. MB may be useful to delay mitochondrial dysfunction and oxidative stress, which are thought to be key aberrations that lead to cellular senescence and aging and the decrease in complex I in Parkinson’s disease and complex IV in Alzheimer’s disease (527).
Selected Publications
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317. Ames BN, Shigenaga MK, and Hagen TM (1993) Oxidants, Antioxidants, and the Degenerative Diseases of Aging. Proc. Natl. Acad. Sci. USA 90:7915-22.
338. Shigenaga MK, Hagen TM, and Ames BN (1994) Oxidative Damage and Mitochondrial Decay in Aging. Proc. Natl. Acad. Sci. USA 91:10771-8.
347. Ames BN, Shigenaga MK, and Hagen TM (1995) Mitochondrial Decay in Aging. Biochim. Biophys. Acta. 1271:165-70.
358. Beckman KB, and Ames BN (1996) Detection and Quantification of Oxidative Adducts of Mitochondrial DNA. Methods Enzymol. 264:442-53.
377. Christen S, Woodall AA, Shigenaga MK, Southwell-Keely PT, Duncan MW, and Ames BN (1997) γ-Tocopherol Traps Mutagenic Electrophiles such as NOx and Complements α-Tocopherol: Physiological Implications. Proc. Natl. Acad. Sci. USA 94:3217-22.
379. Hagen TM, Yowe DL, Bartholomew JC, Wehr CM, Do KL, Park J-Y, and Ames BN (1997) Mitochondrial Decay in Hepatocytes from Old Rats: Membrane Potential Declines, Heterogeneity and Oxidants Increase. Proc. Natl. Acad. Sci. USA 94:3064-9.
385. Beckman KB, and Ames BN (1997) Oxidative Decay of DNA. J. Biol. Chem. 272: 19633-6.
394. Beckman KB, and Ames BN (1998) The Free Radical Theory of Aging Matures. Physiol. Rev. 78:547-81.
398. Yowe DL, and Ames BN (1998) Quantitation of Age-related Mitochondrial DNA Deletions in Rat Tissues Shows their Pattern of Accumulation Differs from that of Humans. Gene 209:23-30.
405. Lykkesfeldt J, Hagen TM, Vinarsky V, and Ames BN (1998) Age-associated Decline in Ascorbic Acid Concentration, Recycling and Biosynthesis in Rat Hepatocytes - Reversal with (R)-α-Lipoic Acid Supplementation. FASEB J.12:1183-9.
408. Hagen TM, Ingersoll RT, Wehr CM, Lykkesfeldt J, Vinarsky V, Bartholomew JC, Song MH, and Ames BN (1998) Acetyl-L-Carnitine Fed to Old Rats Partially Restores Mitochondrial Function and Ambulatory Activity. Proc. Natl. Acad. Sci. USA 95:9562-6.
409. Lykkesfeldt J, and Ames BN (1999) Ascorbic Acid Recycling in Rat Hepatocytes as a Measurement of Antioxidant Capacity: Decline with Age. In: Methods in Enzymology, L. Packer, ed. (Academic Press, San Diego, Ca), vol. 299, pp 83-7.
415. Beckman KB, and Ames BN (1999) Endogenous Oxidative Damage of mtDNA. Mutat. Res. 424:51-8.
416. Hagen TM, Ingersoll RT, Liu J, Lykkesfeldt J, Wehr CM, Vinarsky V, Bartholomew JC, and Ames BN (1999) (R)-α-Lipoic Acid-Supplemented Old Rats Have Improved Mitochondrial Function, Decreased Oxidative Damage, and Increased Metabolic Rate. FASEB J. 13:411-8.
427. Knutson MD, Walter PB, Ames BN, and Viteri FE (2000) Both Iron Deficiency and Daily Iron Supplements Increase Lipid Peroxidation in Rats. J. Nutr. 130:621-8.
433. Hagen TM, Vinarsky V, Wehr CM, and Ames BN (2000) (R)-α-Lipoic Acid Reverses the Age-Associated Increase in Susceptibility of Hepatocytes to tert-Butylhydroperoxide both In Vitro and In Vivo. Antiox. & Redox Signal. 2:473-83.
435. Jiang Q, Elson-Schwab I, Courtemanche C, and Ames BN (2000) γ-Tocopherol and its Major Metabolite, in Contrast to α-Tocopherol, Inhibit Cyclooxgenase Activity in Macrophages and Epithelial Cells. Proc. Natl. Acad. Sci. USA. 97:11494-9.
444. Wallock LM, Tamura T, Mayr CA, Johnston KE, Ames BN, and Jacob RA (2001) Low Seminal Plasma Folate Concentrations are Associated with Low Sperm Density and Count in Male Smokers and Nonsmokers. Fertil. & Steril. 75:252-9.
446. Jiang Q, Christen S, Shigenaga MK, and Ames BN (2001) γ-Tocopherol, the Major Form of Vitamin E in the US Diet, Deserves More Attention. Am. J. Clin. Nutr. 74:714-22.
451. Walter PB, Knutson MD, Paler-Martinez A, Lee S, Xu Y, Viteri FE, and Ames BN (2002) Iron Deficiency and Iron Excess Damage Mitochondria and Mitochondrial DNA in Rats. Proc. Natl. Acad. Sci. USA. 99:2264-69.
453. Ames BN, Elson-Schwab I, and Silver E (2002) High-Dose Vitamins Stimulate Variant Enzymes with Decreased Coenzyme-Binding Affinity (Increased Km): Relevance to Genetic Disease and Polymorphisms. Am J. Clin. Nutr. 75:616-58.
454. Liu J, Head E, Gharib AM, Yuan W, Ingersoll RT, Hagen TM, Cotman CW, and Ames BN (2002) Memory Loss in Old Rats is Associated with Brain Mitochondrial Decay and RNA/DNA Oxidation: Partial Reversal by Feeding Acetyl-L-Carnitine and/or R-α-Lipoic Acid. Proc. Natl. Acad. Sci. USA. 99:2356-61.
455. Hagen TM, Liu J, Lykkesfeldt J, Wehr CM, Ingersoll RT, Vinarsky V, Bartholomew JC, and Ames BN (2002) Feeding Acetyl-L-Carnitine and Lipoic Acid to Old Rats Significantly Improves Metabolic Function while Decreasing Oxidative Stress. Proc. Natl. Acad. Sci. USA. 99:1870-5.
456. Liu J, Killilea DW, and Ames BN (2002) Age-associated Mitochondrial Oxidative Decay: Improvement of Carnitine Acetyltransferase Substrate Binding Affinity and Activity in Brain by Feeding Old Rats Acetyl-L-Carnitine and/or R-α-Lipoic Acid. Proc. Natl. Acad. Sci. USA 99:1876-81.
459. Jiang Q, Christen S, Shigenaga MK, and Ames BN (2002) γ-Tocopherol: The Neglected Form of Vitamin E: New Functions, New Interest. In: Oxidative Stress and Aging: Advances in Basic Science, Diagnostics and Intervention, R. G. Cutler and H. Rodriguez, eds. (World Scientific Publishing Co., River Edge, NJ), pp 567-79.
463. Ames BN, and Wakimoto P (2002) Are Vitamin and Mineral Deficiencies a Major Cancer Risk? Nat. Rev. Cancer. 2:694-704.
464. Head E, Liu J, Hagen TM, Muggenburg BA, Milgram NW, Ames BN, and Cotman CW (2002) Oxidative Damage Increases with Age in a Canine Model of Human Brain Aging. J. Neurochem. 82:375-81.
465. Jiang Q, Lykkesfeldt J, Shigenaga MK, Shigeno ET, Christen S, and Ames BN (2002) γ-Tocopherol Supplementation Inhibits Protein Nitration and Ascorbate Oxidation in Rats with Inflammation. Free Radic. Biol. Med. 33:1534-42.
466. Christen S, Jiang Q, Shigenaga MK, and Ames BN (2002) Analysis of Plasma Tocopherols α-, γ-, and 5-Nitro-γ-Tocopherol, in Rats with Inflammation by HPLC Coulometric Detection. J. Lipid Res. 43:1978-85.
468. Ho E, and Ames BN (2002) Low intracellular zinc induces oxidative DNA damage, disrupts p53, NFκB and AP1 DNA Binding, and Affects DNA Repair in a Rat Glioma Cell Line. Proc Natl Acad Sci USA 99:16770-5.
473. Jacob RA, Aiello GM, Stephensen CB, Blumberg JB, Milbury PE, Wallock LM, and Ames BN (2003) Moderate Antioxidant Supplementation has no Effect on Biomarkers of Oxidant Damage in Healthy Men with Low Fruit and Vegetable Intakes. J. Nutr. 133:740-3.
479. Ho E, Courtemanche C, and Ames BN (2003) Zinc deficiency induces oxidative DNA damage and increases P53 expression in human lung fibroblasts. J. Nutr. 133:2543-8.
482. Courtemanche C, Huang AC, Elson-Schwab I, Kerry N, Ng BY, and Ames BN (2004) Folate deficiency and ionizing radiation cause DNA breaks in primary human lymphocytes: a comparison. FASEB J. 18:209-11.
484. Ames BN (2004) Mitochondrial Decay, A Major Cause of Aging, Can Be Delayed. J. Alz. Dis. 6:117-21.
490. Ames BN, and Liu J (2004) Delaying the Mitochondrial Decay of Aging with Acetyl Carnitine. Ann NY Acad Sci. 1033:108-16.
491. Courtemanche C, Elson-Schwab I, Mashiyama ST, Kerry N, and Ames BN (2004) Folate deficiency inhibits the proliferation of primary human CD8+ T lymphocytes in vitro. J Immunol. 173:3186-92.
492. Jiang Q, Wong J, and Ames BN (2004) γ-Tocopherol induces apoptosis in androgen-responsive LNCaP prostate cancer cells via caspase dependent and independent mechanism. Ann NY Acad Sci. 1031:399-400.
493. Jiang Q, Wong J, Fyrst H, Saba JD, and Ames BN (2004) γ-Tocopherol, or Combinations of Vitamin E Forms, Induce Cell Death In Human Prostate Cancer Cells By Interrupting Sphingolipid Synthesis. Proc Natl Acad Sci USA, 101:17825-30.
498. McCann JC, and Ames BN (2005) Is docosahexaenoic acid (DHA), an n-3 long chain polyunsaturated fatty acid, required for normal brain function? An overview of evidence from cognitive and behavioral tests in humans and animals: a review. Am J Clin Nutr. 82:281-95.
499. Voloboueva LA, Liu J, Suh JH, Ames BN, and Miller SS (2005) (R)-α-Lipoic Acid Protects Retinal Pigment Epithelial Cells From Oxidative Damage Invest. Ophthalmol. Vis. Sci.46:4302-10.
504. Ames BN, Atamna H, and Killilea D (2005) Review: Mineral and Vitamin Deficiencies Can Accelerate the Mitochondrial Decay of Aging. Mol. Aspects Med. 26:363-78.
507. Ames BN, Suh J, and Liu J (2006) Enzymes Lose Binding Affinity (increase Km) for Coenzymes and Substrates with Age: A Strategy for Remediation. In: Nutritional Genomics: Discovering the Path to Personalized Nutrition. Kaput, J. and Rodriguez, RL. (Eds). John Wiley and Sons, Inc., Hoboken, NJ. pp. 277-91.
508. McCann J, Hudes M, and Ames BN (2006). An Overview of Evidence for a Causal Relationship Between Dietary Availability of Choline During Development and Cognitive Function in Offspring. Neurosci Biobehav Rev. 30:696-712.
509. McCann J, and Ames BN (2006) Letter to the Editor (Response to P. Wainwright): Scientific Precision and Deciding Whether to Supplement Infant Formulas With LCPUFAs. Am J Clin Nutr. 83:920-1.
510. Ames BN (2006) Low micronutrient intake may accelerate the degenerative diseases of aging through allocation of scarce micronutrients by triage. Proc. Natl. Acad. Sciences, USA, 103:17589-94.
511. Jia L, Liu Z, Miller SS, Ames BN, and Liu J (2007) (R)-α-Lipoic acid protects retinal pigment epithelial cells from damage by acrolein, a toxin in cigarette smoke: Relevance to macular degeneration. Invest. Ophthalmol. Vis. Sci. 48:339-48.
512. Atamna H, Newberry J, Erlitzki R, Schultz CS, and Ames BN (2007) Biotin Deficiency Inhibits Heme Synthesis and Impairs Mitochondria in Human Lung Fibroblasts. J of Nutr. 137:25-30.
514. McCann J, and Ames BN. (2007) An Overview of Evidence For a Causal Relationship Between Iron Deficiency During Development and Deficits in Cognition or Behavior. Am J Clin Nutr. 85:931-45.
515a. McMackin CJ, Widlansky ME, Hamburg NM, Huang AL, Weller S, Holbrook M, Gokce N, Hagen TM, Keaney JF Jr, and Vita JA (2007) Effect of combined treatment with alpha-Lipoic acid and acetyl-L-carnitine on vascular function and blood pressure in patients with coronary artery disease. J Clin Hypertens (Greenwich) 9:249-55.
516. McCann JC, and Ames BN (2007) DHA and Cognitive Development. Pediatric Basics 117: 16-22.
517. Ames BN, McCann JC, Stampfer MJ, and Willett WC (2007) Letter to the Editor: Evidence-based decision making on micronutrients and chronic disease: long-term randomized controlled trails are not enough. Amer J Clin Nutr. 86:522-3.
518. Wagner JG, Jiang Q, Harkema JR, Illek B, Patel DD, Ames BN, and Peden DB (2007) Ozone Enhancement of Lower Airway Allergic Inflammation is Prevented By γ-Tocopherol. Free Radic. Biol. Med. 43:1176-88.
519. Milgram NW, Araujo JA, Hagen TM, Treadwell BV, and Ames BN (2007) Acetyl-L-carnitine and a-lipoic acid supplementation of aged beagle dogs improves learning in two landmark discrimination tests. FASEB J. 21:3756-62.
520. McCann JC, and Ames BN (2007) Lessons from DHA trials on cognition/behavior in humans and animals (in Dutch). In: Special Fatty Acids. Scientific publication on infant nutrition (ed. FAJ Muskiet). Elsevier Health Care, The Netherlands, pp 15-7.
525. Wagner JG, Jiang Q, Harkema JR, Ames BN, Illek B, Roubey RA, and Peden DB (2008) γ-Tocopherol prevents airway eosinophilia and mucous cell hyperplasia in experimentally induced allergic rhinitis and asthma. Clin & Exp Allergy 38:501-11.
527. Atamna H, Nguyen A, Schultz C, Boyle K, Newberry J, Kato H, Ames BN (2008) Methylene Blue Delays Cellular Senescence and Enhances Key Mitochondrial Biochemical Pathways Relevant to Aging. FASEB J. 22:703-12.
528. McCann, JC, and Ames BN (2008) Review Article: Is there convincing biological or behavioral evidence linking vitamin D deficiency to brain dysfunction? FASEB J. 22: 982-1001.
530. King SM, Donangelo CM, Knutson MD, Walter PB, Ames BN, Viteri FE, and King JC (2008) Daily Supplementation With Iron Increases Lipid Peroxidation In Young Women With Low Iron Stores. Exp Biol & Med. in press.
531. Killilea DW and Ames BN (2008) Magnesium Deficiency Accelerates Cellular Senescence In Cultured Human Fibroblasts. Proc Natl Acad Sci USA. 105:5768-5773.
Last Updated 2008-05-27