Amino Acids

, Volume 13, Issue 2, pp 91–103 | Cite as

Dietary tryptophan and aging

  • H. Sidransky
Review Article


This paper considers findings which may relate to whether there may be a correlation between dietary L-tryptophan and aging. Early studies had reported that animals fed a tryptophan-deficient diet showed increased longevity compared to controls. Although decreased serotonin levels due to the tryptophan-deficient diet was considered of importance for the increased longevity, a more likely explanation was decreased diet intake due to the deficient diet. Indeed, decreased diet consumption as well as decreased energy intake have been shown to lengthen the lifespan of animals. Greater quantitative assessment between the effect of a tryptophan-deficient diet and that of decreased energy intake needs to be obtained. Our recent findings that one mouse strain (NZBWF1), which is autoimmune susceptible and has a relatively short lifespan, demonstrate a significantly decreased binding affinity for L-tryptophan by hepatic nuclei when compared to other mouse strains are of much interest. These results stimulated us to reconsider the issue whether L-tryptophan itself may influence the aging process. Since L-tryptophan has a regulatory effect on hepatic protein synthesis which may be related to its binding to a specific nuclear receptor, much akin to what occurs with certain steroid hormones which are considered to be involved in the aging process, this review explores the possibility that L-tryptophan via its regulatory action may be of great importance and merits further investigation. This indispensible dietary component may have a vital regulatory control in the normal state and possibly also during the process of aging.


Tryptophan Regulatory Control Aging Process Mouse Strain Nuclear Receptor 
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  1. Albanese AA, Holt Jr LE, Kajdi CN, Frankston JE (1943) Observations on tryptophane deficiency in rats. Chemical and morphological changes in the blood. J Biol Chem 148: 299–309Google Scholar
  2. Ballard FJ, Hopgood MF (1973) Phosphopyruvate carboxylase induction by L-tryptophan: effects on synthesis and degradation of the enzyme. Biochem J 136: 259-264PubMedGoogle Scholar
  3. Beato M, Herrlech P, Schutz G (1995) Steriod hormone receptors: many actors in search of a plot. Cell 83: 851–857PubMedGoogle Scholar
  4. Belongia EA, Mayeno AN, Osterholm MT (1992) The eosinophilia-myalgia syndrome and tryptophan. Annu Rev Nutr 12: 235–256PubMedGoogle Scholar
  5. Berg BN (1960) Nutrition and longevity in the rat. I. Food intake in relation to size, health and fertility. J Nutr 71: 242–254PubMedGoogle Scholar
  6. Berg BN, Simms HS (1960) Nutrition and longevity in the rat. II. Longevity and onset of disease with different levels of food intake. J Nutr 71: 255–263PubMedGoogle Scholar
  7. Brtko J, Filipcik P (1994) Effect of selenite and selenate on rat liver nuclear 3,5,3′-triiodothyronine (T3) receptor. Biol Trace Elem Res 41: 191–199PubMedGoogle Scholar
  8. Chee PY, Swick RW (1976) Effect of dietary protein and tryptophan on the turnover of rat liver ornithine aminotransferase. J Biol Chem 251: 1029–1034PubMedGoogle Scholar
  9. Cihak A (1979) L-tryptophan action on hepatic RNA synthesis and enzyme induction. Mol Cell Biochem 24:131–142PubMedGoogle Scholar
  10. Cole AS, Scott PP (1954) Tissue changes in the adult tryptophan-deficient rat. Br J Nutr 8: 125–138PubMedGoogle Scholar
  11. Cole GM, Segall PE, Timiras PS (1982) Hormones during aging. In: Vernadaker A, Timiras PS, (eds) Hormones in development and aging. SP Medica and Scientific Books, New York, pp 477–550Google Scholar
  12. Cook JR, Beutow DE (1981) Decreased protein synthesis by polysomes, tRNA and aminoacyls-tRNA synthetases isolated from senescent rat liver. Mech Ageing Dev 17: 41–52PubMedGoogle Scholar
  13. Cosgrove JW, Verney E, Schwartz AM, Sidransky H (1992) Tryptophan binding to nuclei of rat brain. Exp Mol Pathol 57: 180–192PubMedGoogle Scholar
  14. DeMarte ML, Enesco HE (1986) Influence of low tryptophan diet on survival and organ growth in mice. Mech Ageing Dev 36: 161–171PubMedGoogle Scholar
  15. Demling J, Langer K, Mehr MQ (1996) Age dependence of large neural amino acid levels in plasma. Focus on tryptophan. Adv Exp Med Biol 398: 579–582PubMedGoogle Scholar
  16. Felig P (1975) Amino acid metabolism in man. Annu Rev Biochem 44: 933–955PubMedGoogle Scholar
  17. Fuchs D, Foreman A, Hagberg L, et al (1990) Immune activation and decreased tryptophan in patients with HIV-1 infection. J Interferon Res 10: 599–603PubMedGoogle Scholar
  18. Garrett CT, Cairns V, Murty CN (1984) Effect of tryptophan on informosomal and polyribosome associated messenger RNA in rat liver. J Nutr 114: 50–57PubMedGoogle Scholar
  19. Garrison PM, Tulles K, Aarls JMMJ, et al (1996) Species-specific recombinant cell lines as bioassay systems for the detection of 2,3,7,8-tetrachloridibenzo-p-dioxin-like chemicals. Fundamental Appl Toxicol 30: 194–203Google Scholar
  20. Kalimi M (1984) Glucocorticoid receptors: from development to aging. Mech Ageing Dev 24: 129–138PubMedGoogle Scholar
  21. Kalimi M, Beato M, Feigelson P (1973) Interaction of glucocorticoids with rat liver nuclei. I. Role of the cytosol protein. Biochemistry 12: 3365–3371PubMedGoogle Scholar
  22. Kanungo MS (1980) Biochemistry of ageing: changes in enzymes during ageing. Academic Press, London, pp 79–126Google Scholar
  23. Kaplan JH, Pitot HC (1970) The regulation of intermediary amino acid metabolism in animal tissues. In: Munro HN (ed) Mammalian protein metabolism, vol 4. Academic Press, New York, pp 387–443Google Scholar
  24. Kaufmann SH, Okret S, Wikstrom AC, et al (1986) Binding of the glucocorticoid receptor to the rat liver nuclear matrix. The role of disulfide bond formation. J Biol Chem 261: 11962–11967PubMedGoogle Scholar
  25. Kilberg MS, Hutson RG, Laine RO (1994) Amino acid-regulated gene expression in eukaryotic cells. FASEB J 8: 13–19PubMedGoogle Scholar
  26. Kurl RN, Verney E, Sidransky H (1987) Tryptophan binding sites on nuclear envelopes of rat liver. Nutr Rep Int 36: 669–677Google Scholar
  27. Kurl RN, Verney E, Sidransky H (1988) Identification and immunohistochemical localization of a tryptophan binding protein in nuclear envelopes of rat liver. Arch Biochem Biophys 265: 286–293PubMedGoogle Scholar
  28. Kurl RN, Barsoum AL, Sidransky H (1992) Association of poly(A)polymerase with tryptophan receptor in rat hepatic nuclei. J Nutr Biochem 3: 366–372Google Scholar
  29. Kurl RN, Verney E, Sidransky H (1993) Effect of tryptophan on rat hepatic nuclear poly(A)polymerase activity. Amino Acids 5: 263–271Google Scholar
  30. Lefebore YA, Novosad Z (1980) Binding of androgens to a nuclear-envelope fraction from the rat ventral prostate. Biochem J 186: 641–647PubMedGoogle Scholar
  31. Margarity M, Valcana T, Timiras PS (1985) Thyroxine diiodination, cytoplasmic distribution and nuclear binding of thyroxine and diiodothyronine in liver and brain of young and old rats. Mech Ageing Dev 29: 181–189PubMedGoogle Scholar
  32. McCay CM (1952) Chemical aspects of aging and the effect of diet upon aging. In: Liansing AI (ed) Cowdry's problems of ageing, 3rd edn. Williams & Wilkins, Baltimore, p 139Google Scholar
  33. Murty CN (1985) Effects of nutrition on transcriptional and translational controls of protein synthesis in liver. In: Sidransky H (ed) Nutritional pathology, pathobiochemistry of dietary imbalances. Dekker, New York, pp 63–113Google Scholar
  34. Murty CN, Sidransky H (1972) The effect of tryptophan on messenger RNA of the liver of fasted mice. Biochim Biophys Acta 262: 328–335PubMedGoogle Scholar
  35. Murty CN, Verney E, Sidransky H (1976) Effect of tryptophan on polyriboadenylic acid and polyadenylic acid-messenger ribonucleic acid in rat liver. Lab Invest 34: 77–85PubMedGoogle Scholar
  36. Murty CN, Verney E, Sidransky H (1977) The effect of tryptophan on nucleocytoplasmic translocation of RNA in rat liver. Biochim Biophys Acta 747: 117–128Google Scholar
  37. Murty CN, Verney E, Sidransky H (1979) In vivo and in vitro studies on the effects of tryptophan on translocation of RNA from nuclei on rat liver. Biochem Med 22: 98–109PubMedGoogle Scholar
  38. Murty CN, Hornseth R, Verney E, Sidransky H (1983) Effect of tryptophan on enzymes and proteins of hepatic nuclear envelopes of rats. Lab Invest 48: 256–262PubMedGoogle Scholar
  39. Naito H, Kandatsu M (1970) Effect of essential amino acid-deficiency on protein nutrition. Part III. Incorporation of35S-methionine into the tissues of rats fed on tryptophan-deficiency. Agric Biol Chem 34: 1078–1083Google Scholar
  40. Navab F, Winter CG (1988) Effect of aging on intestinal absorption of aromatic amino acids in vitro in the rat. Am J Physiol 254: 6631–6636Google Scholar
  41. Osborne TB, Mendel LB (1914) Amino acids in nutrition and growth. J Biol Chem 17: 325–349Google Scholar
  42. Poston HA, Rumsey GL (1983) Factors affecting dietary requirement and deficiency, signs of L-tryptophan in rainbow trout. J Nutr 113: 2568–2577PubMedGoogle Scholar
  43. Ross MH (1972) Length of life and caloric intake. Am J Clin Nutr 25: 834–838PubMedGoogle Scholar
  44. Roth GS (1974) Age-related changes in specific glucocorticoid binding by steroid-responsive tissues of rats. Endocrinology 94: 82–90PubMedGoogle Scholar
  45. Sainio EL, Pulkki K, Young SN (1996) L-tryptophan: biomedical, nutritional and pharmacological aspects. Amino Acids 10: 21–47Google Scholar
  46. Samuels LT, Goldthorpe HC, Dougherty TF (1951) Metabolic effects of specific amino acid deficiencies. Fed Proc 10: 393Google Scholar
  47. Sap J, Munoz A, Damm K, Goldberg Y, et al (1986) The C-erb-A protein is a high affinity receptor for thyroid hormone. Nature 324: 635–640PubMedGoogle Scholar
  48. Schimke RT, Sweeney EW, Berlin CM (1965) The roles of synthesis and degradation in the control of rat liver tryptophan pyrrolase. J Biol Chem 240: 322–331PubMedGoogle Scholar
  49. Schroder HC, Wenger R, Gerner H, et al (1989) Suppression of the modulatory effects of the antileukemic and anti-human immunodeficiency virus compound avarol on gene expression by tryptophan. Cancer Res 49: 2069–2076PubMedGoogle Scholar
  50. Segall PE (1979) Interrelations of dietary and hormonal effects in aging. Mech Ageing Dev 9: 515–525PubMedGoogle Scholar
  51. Segall PE, Timiras PS (1976) Patho-physiologic findings after chronic tryptophan deficiency in rats. A model for delayed growth and aging. Mech Ageing Dev 5: 109–124PubMedGoogle Scholar
  52. Sharma R, Timiras PS (1987) Age-dependent regulation of glucocorticoid receptors in the liver of male rats. Biochim Biophys Acta 930: 237–243PubMedGoogle Scholar
  53. Sidransky H (1972) Chemical and cellular pathology of experimental acute amino acid deficiency. Meth Achievm Exp Path 6: 1–24Google Scholar
  54. Sidransky H (1985) Tryptophan, unique action by an essential amino acid. In: Sidransky H (ed) Nutritional pathology. Pathobiochemistry of dietary imbalances. Dekker, New York, pp 1–62Google Scholar
  55. Sidransky H (1994) Eosinophilia-myalgia syndrome: a recent syndrome serving as an alert to new diseases ahead. Mod Pathol 7: 806–810PubMedGoogle Scholar
  56. Sidransky H, Verney E (1970) Enhanced hepatic protein synthesis in rats force-fed a tryptophan-devoid diet. Proc Soc Exp Biol Med 135: 618–622PubMedGoogle Scholar
  57. Sidransky H, Verney E (1971) Alterations in hepatic polyribosomes after fasting as a function of age. Nutr Rep Inter 3: 389–394Google Scholar
  58. Sidransky H, Verney E (1988) Effect of tryptophan on livers of pregnant and lactating rats and their fetuses and pups. Proc Soc Exp Biol Med 187: 309–314PubMedGoogle Scholar
  59. Sidransky H, Verney E (1994) Comparative studies on tryptophan binding to hepatic nuclear envelopes in Sprague-Dawley and Lewis rats. Am J Physiol 36: R502-R507Google Scholar
  60. Sidransky H, Verney E (1996a) Influence of L-alanine on effects induced by L-tryptophan on rat liver. J Nutr Biochem 7: 200–206Google Scholar
  61. Sidransky H, Verney E (1996b) The presence of thiols in the hepatic nuclear binding site for L-tryptophan: studies with selenite. Nutr Res 16: 1023–1034Google Scholar
  62. Sidransky H, Verney E (1997a) Differences in tryptophan binding to hepatic nuclei of NZBWF1 and Swiss mice: insight into mechanism of tryptophan's effects. J Nutr 127: 270–275PubMedGoogle Scholar
  63. Sidransky H, Verney E (1997b) L-tryptophan binding to hepatic nuclei: age and species differences. Amino Acids 12: 77–84Google Scholar
  64. Sidransky H, Murty CN, Verney E (1984) Nutritional control of protein synthesis. Studies relating to tryptophan-induced stimulation of nucleocytoplasmic translocation of mRNA in rat liver. Am J Pathol 117: 298–309PubMedGoogle Scholar
  65. Sidransky H, Murty CN, Verney E (1986) Evidence for the role of glycosylation of proteins in the tryptophan-induced stimulation of nucleocytoplasmic translocation of mRNA in rat liver. Lab Invest 54: 93–99PubMedGoogle Scholar
  66. Sidransky H, Verney E, Kurl RN (1990) Comparison of effects of L-tryptophan and a tryptophan analog, D, L-β-(1-naphthyl)alanine on processes relating to hepatic protein synthesis in rats. J Nutr 120: 1157–1162PubMedGoogle Scholar
  67. Sidransky H, Verney E, Cosgrove JW, et al (1994) Studies with 1,1′ ethylidenebis (tryptophan); a contaminant associated with L-tryptophan implicated in the eosinophilia-myalgia syndrome. Toxicol Appl Pharmacol 126: 108–113PubMedGoogle Scholar
  68. Sidransky H, Kurl RN, Holmes SC, Verney E (1995) Tryptophan binding to nuclei of rat liver and hepatoma. J Nutr Biochem 6: 73–79Google Scholar
  69. Simmer RCM, Means AR, Clark JH (1984) Estrogen modulation of nuclear-associated steroid hormone binding. Endocrinology 115: 1197–1202PubMedGoogle Scholar
  70. Sydenstricker VP, Hall WK, Bowles LL, Schmidt Jr HL (1947) The corneal vascularization resulting from deficiencies of amino acids in the rat. J Nutr 34: 481–490Google Scholar
  71. Tang JP, Melethil S (1995) Effect of aging on the kinetics of blood-brain barrier uptake of tryptophan in rats. Pharm Res 12: 1085–1091PubMedGoogle Scholar
  72. Tashima Y, Terui M, Itoh H, et al (1989) Effect of selenite on glucocorticoid receptor. J Biochim 105:358–361Google Scholar
  73. Thompson CC, Evans RM (1989) Transactivation by thyroid hormone receptors: functional parallels with steroid hormone receptors. Proc Natl Acad Sci 86: 3494–3498PubMedGoogle Scholar
  74. Totter JR, Day PL (1942) Cataract and other ocular changes resulting from tryptophane deficiency. J Nutr 24: 159–166Google Scholar
  75. Unkila M, Ruotsalainen M, Pohjanvvirta R, et al (1995) Effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on tryptophan and glucose homostasis in the most TCDD-susceptible and the most TCDD-resistent species, guinea pigs and hamsters. Arch Toxicol 69: 677–683PubMedGoogle Scholar
  76. Valcana T (1979) The role of triiodothyronine in brain development. In: Meisami E, Brazier MAB (eds) Neural growth and differentiation. Raven Press, New York, pp 39–58Google Scholar
  77. Valcana T, Timiras PS (1978) Nuclear triodothyronine receptors in the developing brain. Mol Cell Endocrinoi 11: 31–41Google Scholar
  78. Van Pilsum JF, Speyer JF, Samuels LT (1957) Essential amino acid deficiency and enzyme activity. Arch Biochem 68: 42–53PubMedGoogle Scholar
  79. Viskup RN, Baker M, Holbrook JP, Penneall R (1979) Age-associated changes in activities of rat hepatocytes. I. Protein synthesis. Exp Aging Res 5: 487–496PubMedGoogle Scholar
  80. Weinberger C, Thompson CC, Ong ES, Lebo R, et al (1986) The c-erb-A gene encodes a thyroid hormone receptor. Nature 324: 641–646PubMedGoogle Scholar
  81. Willcock EG, Hopkins FG (1906) The importance of individual amino acids in metabolism. Observations on the effect of adding tryptophane to a dietary in which zero is the sole nitrogenous constituent. J Physiol 35: 88–102Google Scholar
  82. Yunis EJ, Teague PO, Stutman O, Good RA (1972) The thymus, autoimmunity and the involution of the lymphoid system. In: Sigel MM (ed) Tolerance autoimmunity, and aging. CC Thomas, Springfied, pp 62–119Google Scholar

Copyright information

© Springer-Verlag 1997

Authors and Affiliations

  • H. Sidransky
    • 1
  1. 1.Department of Pathology, Ross 502George Washington University Medical CenterWashingtonUSA

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