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Age-associated changes in gene expression patterns in the liver

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Journal of Gastrointestinal Surgery Aims and scope

Abstract

Aging is one of the least clearly understood biological processes. Alteration of oxidation/reduction (redox) enzymes has been demonstrated with aging; however, a systematic analysis of expression patterns has not been performed. The liver plays a key role in homeostasis and detoxification; therefore alteration of hepatic gene expression with aging may affect outcome after surgery. The purpose of our study was to assess changes in gene expression patterns in aged livers from both rats and humans using gene array analysis. Total RNA was extracted from young (2-month-old) and aged (2-year-old) rat livers, as well as young (1-year-old) and aged (78-year-old) human livers. Gene expression patterns were compared using Affymetrix GeneChip arrays. The expression pattern of selected genes was confirmed by reverse transcription-polymerase chain reaction. A threefold or greater change in gene expression was noted in 582 genes in the aged rat livers and 192 genes in the aged human livers. Comparison of the genes that were increased with aging demonstrated some similar patterns of expression in the rat and human livers, particularly in members of the antioxidant family and the cytochrome P-450 genes. Our findings demonstrate changes in the expression pattern of genes in the liver with aging. Concomitant increases in the expression of important antioxidant and detoxifying genes were noted in the livers of both rats and humans. This induction pattern suggests a complex link between changing hepatic detoxification/redox capability and senescence.

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References

  1. Day JC. Population projections of the United States by age, sex, race and Hispanic origin: 1993–2050. In Current Population Reports. Washington, D.C.:U.S. Department of Commerce Bureau of the Census, 1993, pp 25–1104.

    Google Scholar 

  2. Anonymous. CDC Advance Data No. 301. Atlanta, Centers for Disease Control and Prevention: August 31, 1998.

  3. Rosenthal RA, Zenilman ME. Surgery in the elderly. In Townsend CM Jr, Beauchamp RD, Evers BM, Mattox KL, eds. Sabiston Textbook of Surgery, 16th ed. Philadelphia: WB Saunders, 2001, pp 226–246.

    Google Scholar 

  4. Powers JH. Surgery of the Aged and Debilitated. Philadelphia: WB Saunders, 1968.

    Google Scholar 

  5. Zenilman ME. Surgery in the elderly. Curr Probl Surg 1998;35:99–179.

    Article  PubMed  CAS  Google Scholar 

  6. Knight JA. The biochemistry of aging. Adv Clin Chem 2000;35:1–62.

    Article  PubMed  CAS  Google Scholar 

  7. Shigenaga MK, Hagen TM, Ames BN. Oxidative damage and mitochondrial decay in aging. Proc Natl Acad Sci USA 1994;91:10771–10778.

    Article  PubMed  CAS  Google Scholar 

  8. Harman D. Aging: A theory based on free radical and radiation chemistry. J Gerontol 1956;11:298–300.

    PubMed  CAS  Google Scholar 

  9. Yu BP. Cellular defenses against damage from reactive oxygen species. Physiol Rev 1994;74:139–162.

    PubMed  CAS  Google Scholar 

  10. Kristal BS, Yu BP. An emerging hypothesis: Synergistic induction of aging by free radicals and Maillard reactions. J Gerontol 1992;47:B107-B114.

    PubMed  CAS  Google Scholar 

  11. McCord JM, Fridovich I. Superoxide dismutase. An enzymic function for erythrocuprein (hemocuprein). J Biol Chem 1969;244:6049–6055.

    PubMed  CAS  Google Scholar 

  12. Villalba JM, Navas P. Plasma membrane redox system in the control of stress-induced apoptosis. Antioxid Redox Signal 2000;2:213–230.

    Article  PubMed  CAS  Google Scholar 

  13. Ames BN, Shigenaga MK, Hagen TM. Oxidants, antioxidants, and the degenerative diseases of aging. Proc Natl Acad Sci U S A 1993;90:7915–7922.

    Article  PubMed  CAS  Google Scholar 

  14. Amicarelli F, Di Ilio C, Masciocco L, Bonfigli A, Zarivi O, D’Andrea MR, Di Giulio C, Miranda M. Aging and detoxifying enzymes responses to hypoxic or hyperoxic treatment. Mech Ageing Dev 1997;97:215–226.

    Article  PubMed  CAS  Google Scholar 

  15. Grant DM. Detoxification pathways in the liver. J Inherit Metab Dis 1991;14:421–430.

    Article  PubMed  CAS  Google Scholar 

  16. Gonzales FJ. The molecular biology of cytochrome P-450. Pharmacol Rev 1989;40:243–288.

    Google Scholar 

  17. Evers BM, Townsend CM Jr, Thompson JC. Organ physiology of aging. Surg Clin North Am 1994;74:23–39.

    PubMed  CAS  Google Scholar 

  18. Chesky JA, Rockstein M. Life span characteristics in the male Fischer rat. Exp Aging Res 1976;2:399–407.

    Article  PubMed  CAS  Google Scholar 

  19. Chomczynski P, Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem 1987;162:156–159.

    Article  PubMed  CAS  Google Scholar 

  20. Ehlers RA, Kim S, Zhang Y, Ethridge RT, Murrilo C, Hell-mich MR, Evans DB, Townsend CM Jr, Evers BM. Gut peptide receptor expression in human pancreatic cancers. Ann Surg 2000;231:838–848.

    Article  PubMed  CAS  Google Scholar 

  21. Habig WH, Pabst MJ, Jakoby WB. Glutathione S-transferases. The first enzymatic step in mercapturic acid formation. J Biol Chem 1974;249:7130–7139.

    PubMed  CAS  Google Scholar 

  22. Bradford MM. Arapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 1976;72:248–254.

    Article  PubMed  CAS  Google Scholar 

  23. Carrillo MC, Favre C, Carnovale CE, Monti JA, Alvarez ML, Scapini C, Pisani GB, Lugano MC. Involvement of mu class glutathione S-transferase subunit M2 (rGST M2) levels in the initiation and promotion of hepatocellular carcinogenesis in old rats. Exp Gerontol 2001;36:255–265.

    Article  PubMed  CAS  Google Scholar 

  24. Bengton VL, Schaie KW. Handbook of Theories of Aging. New York: Springer, 1999.

    Google Scholar 

  25. Lee CK, Klopp RG, Weindruch R, Prolla TA. Gene expression profile of aging and its retardation by caloric restriction. Science 1999;285:1390–1393.

    Article  PubMed  CAS  Google Scholar 

  26. Ly DH, Lockhart DJ, Lerner RA, Schultz PG. Mitotic misregulation and human aging. Science 2000;287:2486–2492.

    Article  PubMed  CAS  Google Scholar 

  27. Orr WC, Sohal RS. Extension of life-span by overexpression of superoxide dismutase and catalase in Drosophila melanogaster. Science 1994;263:1128–1130.

    Article  PubMed  CAS  Google Scholar 

  28. Larsen PL. Aging and resistance to oxidative damage in Caenorhabditis elegans. Proc Natl Acad Sci U S A 1993;90:8905–8909.

    Article  PubMed  CAS  Google Scholar 

  29. Rao G, Xia E, Richardson A. Effect of age on the expression of antioxidant enzymes in male Fischer F344 rats. Mech Ageing Dev 1990;53:49–60.

    Article  PubMed  CAS  Google Scholar 

  30. Han E, Hilsenbeck SG, Richardson A, Nelson JF. cDNA expression arrays reveal incomplete reversal of age-related changes in gene expression by calorie restriction. Mech Ageing Dev 2000; 115:157–174.

    Article  PubMed  CAS  Google Scholar 

  31. Kensler TW, Taffe BG. Free radicals in tumor promotion. Adv Free Radic Biol Med 1986;2:347–387.

    CAS  Google Scholar 

  32. Oberley LW. Free radicals and diabetes. Free Radic Biol Med 1988;5:113–124.

    Article  PubMed  CAS  Google Scholar 

  33. Semsei I, Rao G, Richardson A. Changes in the expression of superoxide dismutase and catalase as a function of age and dietary restriction. Biochem Biophys Res Commun 1989;164:620–625.

    Article  PubMed  CAS  Google Scholar 

  34. Carillo MC, Kanai S, Sato Y, Kitani K. Age-related changes in antioxidant enzyme activities are region and organ selective as well as sex in the rat. Mech Ageing Dev 1992;65:187–198.

    Article  Google Scholar 

  35. Rikans LE, Moore DR, Snowden CD. Sex-dependent differences in the effects of aging on antioxidant defense mechanisms of rat liver. Biochim Biophys Acta 1991; 1074:195–200.

    PubMed  CAS  Google Scholar 

  36. Ceballos-Picot I, Trivier JM, Nicole A, Sinet PM, Theve-nin M. Age-correlated modifications of copper-zinc superoxide dismutase and glutathione-related enzyme activities in human erythrocytes. Clin Chem 1992;38:66–70.

    PubMed  CAS  Google Scholar 

  37. Imaoka S, Fujita S, Funae Y. Age-dependent expression of cytochrome P-450s in rat liver. Biochim Biophys Acta 1991;1097:187–192.

    PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Surgery, The University of Texas Medical Branch, 301 University Blvd., 77555-0536, Galveston, TX

    Robert P. Thomas M.D. & B. Mark Evers M.D.

  2. The Molecular Genomics Core Laboratory, The University of Texas Medical Branch, Galveston, Texas

    Michelle Guigneaux M.S. & Thomas Wood Ph.D.

Authors
  1. Robert P. Thomas M.D.
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  2. Michelle Guigneaux M.S.
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  3. Thomas Wood Ph.D.
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  4. B. Mark Evers M.D.
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Correspondence to B. Mark Evers M.D..

Additional information

Supported by grants P01 DK35608, R01 AG10885, and T32 DK07639 from the National Institutes of Health. Dr. Thomas is the recipient of a Jeane B. Kempner Scholar Award.

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Thomas, R.P., Guigneaux, M., Wood, T. et al. Age-associated changes in gene expression patterns in the liver. J Gastrointest Surg 6, 445–454 (2002). https://doi.org/10.1016/S1091-255X(01)00010-5

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  • DOI: https://doi.org/10.1016/S1091-255X(01)00010-5

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