K05 Senior Scientist Grant (NCCAM). Ames has published more than 450 publications and consistently ranks among the top few hundred of the most-cited-scientists in all fields; honors include The National Medal of Science & The Japan Prize. Career as pioneer/leader in: gene-regulation; genetic toxicology; mutagenesis; cancer prevention; endogenous oxidants/antioxidants; nutrition and health; mitochondrial decay; and aging. Professor of the Graduate School at U.C. Berkeley. Senior Scientist, Children's Hospital of Oakland Research Institute, with large lab in a newly renovated building. Scientific focus: ramifications of a major review showing that about 50 different human genetic diseases due to a poorer binding affinity (Km) of the mutant enzyme for the coenzyme, can be remedied by feeding high dose B vitamins which raise levels of the corresponding coenzyme; many polymorphisms also have lowered affinity of enzyme for coenzyme. We propose to expand this Km concept by: 1) Testing the effectiveness of high dose B vitamins on phenotypes caused by polymorphisms that affect the Km of enzymes for coenzyme, e.g. homocysteine accumulation in MTHFR: riboflavin; alcohol intolerance in half of Asians: niacin. 2) Testing the effectiveness of other metabolites and micronutrients.3) Determining if mitochondrial oxidative decay with age causes enzymes to lose affinity for their coenzymes and if this can be ameliorated by feeding high doses of B vitamins. Previous results showed that high doses of key mitochondrial metabolites delay mitochondrial decay and involve Km. 4) Minimizing DNA damage and cancer by optimizing micronutrient levels, particularly in the elderly. ? ?

Agency
National Institute of Health (NIH)
Institute
National Center for Complementary & Alternative Medicine (NCCAM)
Type
Research Scientist Award (K05)
Project #
5K05AT001323-02
Application #
6694095
Study Section
Special Emphasis Panel (ZAT1-CP (02))
Program Officer
Hopp, Craig
Project Start
2003-01-01
Project End
2005-12-31
Budget Start
2004-01-01
Budget End
2004-12-31
Support Year
2
Fiscal Year
2004
Total Cost
$256,875
Indirect Cost
Name
Children's Hospital & Res Ctr at Oakland
Department
Type
DUNS #
076536184
City
Oakland
State
CA
Country
United States
Zip Code
94609
Long, Jiangang; Gao, Feng; Tong, Liqi et al. (2009) Mitochondrial decay in the brains of old rats: ameliorating effect of alpha-lipoic acid and acetyl-L-carnitine. Neurochem Res 34:755-63
Mashiyama, Susan T; Hansen, Christine M; Roitman, Esther et al. (2008) An assay for uracil in human DNA at baseline: effect of marginal vitamin B6 deficiency. Anal Biochem 372:21-31
McCann, Joyce C; Ames, Bruce N (2007) An overview of evidence for a causal relation between iron deficiency during development and deficits in cognitive or behavioral function. Am J Clin Nutr 85:931-45
Atamna, Hani; Newberry, Justin; Erlitzki, Ronit et al. (2007) Biotin deficiency inhibits heme synthesis and impairs mitochondria in human lung fibroblasts. J Nutr 137:25-30
Offer, Tal; Ames, Bruce N; Bailey, Steven W et al. (2007) 5-Methyltetrahydrofolate inhibits photosensitization reactions and strand breaks in DNA. FASEB J 21:2101-7
Wallock-Montelius, Lynn M; Villanueva, Jesus A; Chapin, Robert E et al. (2007) Chronic ethanol perturbs testicular folate metabolism and dietary folate deficiency reduces sex hormone levels in the Yucatan micropig. Biol Reprod 76:455-65
Ames, Bruce N (2006) Low micronutrient intake may accelerate the degenerative diseases of aging through allocation of scarce micronutrients by triage. Proc Natl Acad Sci U S A 103:17589-94
McCann, Joyce C; Hudes, Mark; Ames, Bruce N (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
Walter, Patrick B; Fung, Ellen B; Killilea, David W et al. (2006) Oxidative stress and inflammation in iron-overloaded patients with beta-thalassaemia or sickle cell disease. Br J Haematol 135:254-63
Offer, Tal; Ho, Emily; Traber, Maret G et al. (2005) A simple assay for frequency of chromosome breaks and loss (micronuclei) by flow cytometry of human reticulocytes. FASEB J 19:485-7

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