Bruce Ames

Bruce N. Ames

Professor of the Graduate School Division of Biochemistry, Biophysics and Structural Biology

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Research Interests

Vitamin and Mineral Inadequacy Accelerates Aging-Associated Diseases

I posited, and have buttressed, "triage theory" (1,2): metabolism responds to moderate deficiency of an essential vitamin or mineral (V/M) so that the scarce V/M is preferentially retained by V/M-dependent proteins necessary for short-term survival and reproduction. In contrast, proteins needed for long term health, which I term "longevity proteins" because they defend against the diseases associated with aging, lose the V/M and are disabled. Most of the world's population, including that of the U.S., are moderately deficient in one or more of the ~30 essential V/Ms. Moreover, since the damage from moderate deficiency is insidious, its importance for long-term health is not being appreciated. Strong support for triage theory comes from Joyce McCann's analyses of the literature on proteins dependent on vitamin K (3) and on selenium (4). Both have built into metabolism this trade-off between short-term survival and long-term health and each uses a different mechanism to accomplish this end. Theory and evidence suggest that this metabolic trade-off accelerates aging-associated diseases, such as cancer, cognitive decline, and cardiovascular disease. Importantly, by the official U.S. Institute of Medicine measure of inadequacy, the EAR (Estimated Average Requirement; the RDA is set at 2 SD above the EAR), most of the U.S. population is below the EAR for one or more V/M. Taking these long-term triage effects into account in setting EARs could lead to numerous changes. We have calculated from the NHANES database that the percentages of the U.S. population that are below the EAR are: magnesium 56%; zinc 12%; iron 16% of menstruating women; vitamin B6 49% of elderly women; folate 16% of adult women. The U.S. population also has very low intake of vitamin D, calcium, potassium, omega-3 fatty acids, vitamin K, and probably others, and this is especially true for children, adolescents, elders, and the obese. Longevity proteins, about half of those studied, indicate a mechanism that could be used for prevention by monitoring for insidious damage and suggest the existence of an undiscovered class of longevity V/Ms, which we are discovering. Our Choribar (V/M-dense, low-calorie, high-fiber, fruit-based) markedly improves metabolism in many human trials (5).

References:

  1. Ames, B (2006)Proc. Natl. Acad. Sciences, U.S.A., 103:17589-94.
  2. Ames, BN (2010) J Nucleic Acids. doi:10.4061/2010/725071.
  3. McCann JC and Ames BN (2009) Am J Clin Nutr. 90: 889-907. doi: 10.3945/‚Äčajcn.2009.27930.
  4. McCann JC and Ames BN (2011) FASEB J. doi:10.1096/fj.11-180885.
  5. Mietus-Snyder, et al. (2012) FASEB J. published online ahead of print doi:10.1096/fj.11-201558.

Selected Publications

Selected from over 540 publications since 1952. For a complete list of my publications please visit my website: http://www.bruceames.org/bnapublications.php

  1. Martin RG and Ames BN (1961) A Method for Determining the Sedimentation Behavior of Enzymes: Application to Protein Mixtures. J Biol Chem 236:1372-9.
  2. Ames BN, Durston WE, Yamasaki E, and Lee FD (1973) Carcinogens are Mutagens: A Simple Test System Combining Liver Homogenates for Activation and Bacteria for Detection. Proc Natl Acad Sci USA 70:2281-85.
  3. McCann J, Choi E, Yamasaki E, and Ames BN (1975) Detection of Carcinogens as Mutagens in the Salmonella/Microsome Test: Assay of 300 Chemicals. Proc Natl Acad Sci USA 72:5135-9.
  4. Gold LS, Sawyer CB, Magaw R, Backman GM, de Veciana M, Levinson R, Hooper NK, Havender WR, Bernstein L, Peto R, Pike MC, and Ames BN (1984) A Carcinogenic Potency Database of the Standardized Results of Animal Bioassays. Environ Health Perspect 58:9-319.
  5. Ames BN, Gold LS (1990) Chemical Carcinogenesis: Too Many Rodent Carcinogens. Proc Natl Acad Sci USA 87:7772-6.
  6. Blount BC, Mack MM, Wehr C, MacGregor J, Hiatt R, Wang G, Wickramasinghe SN, Everson RB, and Ames BN (1997) Folate Deficiency Causes Uracil Misincorporation into Human DNA and Chromosome Breakage: Implications for Cancer and Neuronal Damage. Proc Natl Acad Sci USA 94:3290-5.
  7. 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.
  8. 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-a-Lipoic Acid. Proc Natl Acad Sci USA99:2356-61.
  9. 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.
  10. Ames B (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.
  11. McCann JM and Ames BN (2009) Vitamin K, an example of triage theory: is micronutrient inadequacy linked to diseases of aging? Am J Clin Nutr 90:1-19.
  12. Ames BN (2010) Optimal micronutrients delay age-associated diseases and mitochondrial decay. Mech Ageing Dev 131:473-9.
  13. Ames BN (2010) Prevention of mutation, cancer, and other age-associated diseases by optimizing micronutrient intake. J Nucleic Acids: DNA Damage, Mutagenesis, and DNA Repairdoi:10.4061/2010/725071. PMC2945683
  14. Lal A and Ames BN (2011) Association of Micronuclei (Chromosome Breaks) with Hematological Diseases and Micronutrient Status. Mutagenesis. 26:57-62. PMC3107612
  15. McCann JC and Ames BN (2011) Adaptive dysfunction of selenoproteins from the perspective of the triage theory: why modest selenium deficiency may increase risk of diseases of aging FASEB J 25:1793-814.
  16. Mietus-Snyder ML, Shigenaga, MK, Suh JH, Shenvi SV, Lal A, McHugh T, Olson D, Lilienstein J, Krauss RM, Gildengoren G, McCann JC, and Ames BN (2012) A micronutrient-dense, high fiber, fruit-based supplement bar increases HDL, particularly large HDL, lowers homocysteine, and raises glutathione in a 2-week trial. FASEB J 26:3515-27. doi:10.1096/fj.11-201558
  17. Trewavas T (2012) Carson no 'beacon of reason' on DDT. Nature 486:473 doi:10.1038/486473a.
Additional webpages: http://www.bruceames.org/ and http://www.chori.org/Principal_Investigators/Ames_Bruce/ames_overview.html

Last Updated 2012-08-22