The Influence of Advanced Age on Cancer Occurrence and Growth

  • William B. Ershler
Part of the Cancer Treatment and Research book series (CTAR, volume 124)

8. Conclusions

It has been said that all medical oncologists, with the exception of those who restrict their practice to pediatric patients, are ‘geriatric oncologists’. This, of course, because the average age of cancer is in excess of 65 years and the median age of most common adult tumors approaches 70 years. Similarly, scientists studying the mechanisms of cancer development and growth are uncovering and elucidating some of the basic molecular and cellular processes of aging. These include the controls of cellular proliferation, mechanisms of DNA repair, and programmed cell death. There are striking voids in our understanding of the basic mechanisms of aging, but one can not help but have the sense that the advances in this field will have the added value of enhancing our understanding of tumor development and growth.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Duthie EH: Physiology of aging: relevance to symptoms, perceptions and treatment tolerance in Comprehensive Geriatric Oncology L. Balducci, G. Lyman and W.B. Ershler (eds). Harwood Academic, Amsterdam, pp 247–262,1998Google Scholar
  2. 2.
    Lindeman RD: Overview: renal physiology and pathophysiology of aging. Am J Kidney Dis 1990, 16(4):275–82PubMedGoogle Scholar
  3. 3.
    Dubrow EL: Reactivation of tuberculosis; a problem of aging. J Am Geriatr Soc 1976; 24(11):481–7PubMedGoogle Scholar
  4. 4.
    Nagami PH, Yoshikawa TT: Tuberculosis in the geriatric patient. J Am Geriatr Soc 1983; 31(6):356–63PubMedGoogle Scholar
  5. 5.
    Gelato MC: Aging and immune function: a possible role for growth hormone. Hormone Res 1996; 45:46–9PubMedGoogle Scholar
  6. 6.
    Arden NH, Patriarca PA, Kendal AP: Experiences in the use and efficacy of inactivated influenza vaccine in the nursing home in Kendal AP, Patriarca PA, eds, Options for the Control of Influenza. New York. Alan Liss, Inc, 1986; 155–68Google Scholar
  7. 7.
    Powers DC, Sears SD, Murphy BR, Thurmar B, Clements ML: Systemic and local antibody responses in elderly subjects give live or inactivated influenza A virus vaccines. J Clin Microbiol 1989; 27:2666–71PubMedGoogle Scholar
  8. 8.
    Hilleman, RM: Realities and enigmas of human viral influenza: pathogenesis, epidemiology and control. Vaccine 2002; 19;20(25–26):3068–87CrossRefGoogle Scholar
  9. 9.
    Kaesberg PR, Ershler WB: The importance of immune senescence in the incidence and malignant properties of cancer in hosts of advanced age. J Gerontology 1989; 44:63–6CrossRefGoogle Scholar
  10. 10.
    Christensen K, Vaupel JW: Determinants of longevity: genetic, environmental and medical factors. J Intern Med 1996; 240(6):333–41PubMedCrossRefGoogle Scholar
  11. 11.
    Guyer B, Strobino DM, Ventura S.J., MacDorman M., Martin JA: Annual summary of vital statistics 1995. Pediatrics 1996; 98(6):1007–19PubMedGoogle Scholar
  12. 12.
    Greville TNE: U.S. life tables by cause of death: 1969–1971. U.S. Decennial Life Tables for 1969–1971 1971; 1:5–15Google Scholar
  13. 13.
    Riggs JE: Longitudinal Gompertzian analysis of adult mortality in the U.S., 1900–1986. Mech Ageing Dev 1990; 54(3):235–47PubMedCrossRefGoogle Scholar
  14. 14.
    Hirsch HR: Can an improved environment cause maximum survival to decrease? Comments on lifespan criteria and longitudinal Gompertzian analysis. Exp Gerontol 1994; 29(2): 119–37PubMedCrossRefGoogle Scholar
  15. 15.
    Orr WC, Sohal RS: Extension of life-span by overexpression of superoxide dismutase and catalase in Drosophila melanogaster. Science 1994; 263(5150): 1128–30PubMedGoogle Scholar
  16. 16.
    Weindruch R: Caloric restriction and aging. Scientific American 1996; 274:46–52.PubMedCrossRefGoogle Scholar
  17. 17.
    Cristofalo VJ, Pignolo, RJ: Replicative senescence of human fibroblast-like cells in culture. Physiol Rev 1993;73:617–38PubMedGoogle Scholar
  18. 18.
    Hayflick L: The limited in vitro lifetime of human diploid cell strains. Exp Cell Res 1965; 37:614–36PubMedCrossRefGoogle Scholar
  19. 19.
    Cristofalo VJ, Palazzo, R., Charpentier, R.L: Limited lifespan of human fibroblasts in vitro: metabolic time or replications? In Adelman RC, Roberts, J., Baker, G.T., ed., Neural Regulatory Mechanisms During Aging. New York: Alan R. Liss, 1980Google Scholar
  20. 20.
    Schneider EL, Mitsui, Y: The relationship between in vitro cellular aging and in vivo human age. Proc Natl Acad Sci USA 1976; 73:3584–88PubMedCrossRefGoogle Scholar
  21. 21.
    Rohme D: Evidence for a relationship between longevity of mammalian species and lif-spans of normal fibroblasts in vitro and erythrocytes in vivo. Proc Natl Acad Sci USA 1976; 78:5009–13CrossRefGoogle Scholar
  22. 22.
    Dimri GP, Lee, X., Basile, G., Acosta, M., Scott, G., Roskelley, C., Medrano, EE, Linskens, M., Rubelj, I., Pereira-Smith, O, Peacocke, M, Campisi, J: A biomarker that identifies senescent human cells in culture and in aging skin in vivo. Proc Natl Acad Sci USA 1995; 92(20):9363–7PubMedCrossRefGoogle Scholar
  23. 23.
    Stjernsward J: Age-dependent tumor host barrier and effect of carcinogen-induced immunodepression on rejection of isografted methylcholanthrene-induced sarcoma cells. J Natl Cancer Inst 1966; 37:505–12PubMedGoogle Scholar
  24. 24.
    Yuhas JM, Pazmino NH, Proctor JO, Toya RE: A direct relationship between immune competence and the subcutaneous growth rate of a malignant murine lung tumor. Cancer Res 1974; 34:722–28PubMedGoogle Scholar
  25. 25.
    Rockwell SC: Effect of host age on transplantation, growth and radiation response of EMT6 tumors. Cancer Research 1981; 41:527–31PubMedGoogle Scholar
  26. 26.
    Gatti RQ, Good RA: Aging, immunity and malignancy. Geriatrics 1979; 25:158–68Google Scholar
  27. 27.
    Bulychev VV: Longevity, atherosclerosis and cellular immunity. Klin Med (Mosk) 1993;71(5):51–4Google Scholar
  28. 28.
    Hansson GK, Libby P, Schonbeck U, Yan ZQ: Innate and adaptive immunity in the pathogenesis of atherosclerosis. Circ Res 2002 23;91:281–91CrossRefGoogle Scholar
  29. 29.
    Lehuen A, Bendelac A, Bach JF, Carnaud C: The nonobese diabetic mouse model. Independent expression of humoral and cell mediated autoimmune features. J Immunol 1990; 144(6):2147–51PubMedGoogle Scholar
  30. 30.
    Hull M, Strauss S, Berger M, Volk B, Bauer J: The participation of interleukin-6, a stress-inducible cytokine, in the pathogenesis of Alzheimer’s disease. Behav Brain Res 1996; 78(1):37–41PubMedCrossRefGoogle Scholar
  31. 31.
    Hull M, Fiebich BL., Lieb S, Berger SS, Volk B, Bauer J: Interleukin-6-associated inflammatory processes in Alzheimer’s disease: New therapeutic options. Neurobiol Aging 1996; 17(5):795–800PubMedCrossRefGoogle Scholar
  32. 32.
    Gillis S, Kozak R, Durante M, Weksler ME: Decreased production and response to T cell growth factor by lymphocytes from aged humans. J Clin Invest 1981; 67:937–42.PubMedCrossRefGoogle Scholar
  33. 33.
    Miller RA: The aging immune system: primer and prospectus. Science 1996; 273(5271):70–4PubMedGoogle Scholar
  34. 34.
    Stephan RP, Sanders VM, Witte PL: Stage-specific alterations in murine lymphopoiesis with age. Int Immunol 1996; 8(4):509–18PubMedGoogle Scholar
  35. 35.
    Radl J, Sepers JM, Skvaril F: Immunoglobulin patterns in humans over 95 years of age. Clin Exp Immunol 1975; 22:84–90PubMedGoogle Scholar
  36. 36.
    Radl J: Animal model of human disease. Benign monoclonal gammopathy (idiopathic paraproteinemia). Am J Pathol 1981; 105(1):91–3PubMedGoogle Scholar
  37. 37.
    Radl J: Age-related monoclonal gammopathies: Clinical lessons from the aging C57BL/6 mouse. Immunol Today 1990; 11:234–6PubMedCrossRefGoogle Scholar
  38. 38.
    Kyle RA: Monoclonal gammopathy of undetermined significance and solitary plasmacytoma. Implications for progression to overt myeloma. Hematol Oncol Clin North Am 1997; 11(1):71–87PubMedCrossRefGoogle Scholar
  39. 39.
    Thoman M, Weigle WO: Lymphokines and aging: Interleukin-2 production and activity in aged animals. J Immunol 1981; 127:2102–6PubMedGoogle Scholar
  40. 40.
    Ershler WB, Sun WH, Binkley N: Interleukin-6 and aging: Blood levels and mononuclear cell production increase with advancing age and in vitro production is modifiable by dietary restriction. Lymphokine Cytokine Res 1993; 12:225–30PubMedGoogle Scholar
  41. 41.
    Ershler WB: Interleukin-6: a cytokine for gerontologists. Journal of the American Geriatrics Society 1993; 41(2):176–81PubMedGoogle Scholar
  42. 42.
    Ershler WB, Keller ET: Age-associated increased IL-6 gene expression, late-life diseases and frailty. Ann Rev Med 2000;51:245–270PubMedCrossRefGoogle Scholar
  43. 43.
    Ershler WB: The influence of an aging immune system on cancer incidence and progression. J Gerontol 1993;48:B3–B7PubMedGoogle Scholar
  44. 44.
    Miller RA: Aging and cancer: another perspective. J Gerontol 1993;48:B8–B10PubMedGoogle Scholar
  45. 45.
    Covelli V, Mouton D, Mojo V et al: Inheritance of immune responsiveness, life span and disease incidence in interline crosses of mice selected for high or low multispecific antibody production. J Immunology 1989;142:1224–1234Google Scholar
  46. 46.
    Imai K, Matsuyama S, Miyake S, Suga K, Nakachi K: Natural cytotoxic activity of peripheral-blood lymphocytes and cancer incidence: an 11-year follow-up study of a general population. Lancet 2000;356:1795–99PubMedCrossRefGoogle Scholar
  47. 47.
    Weinberg RA: Oncogenes and the Molecular Origins of Cancer. Cold Spring Harbor Laboratory Press. 1989Google Scholar
  48. 48.
    Korsemeyer SJ: Programmed cell death: Bcl-2. In: DeVita V.T.; Hellman S.; Rosenberg S.A.: Important Advances in Oncology, 1993. J.B. Lippincott, 1993, 19–28Google Scholar
  49. 49.
    Vogelstein B, Fearon ER, Hamilton SR et al: Genetic alterations during colorectal tumor development. N Engl J Med 1988; 319: 525–532PubMedCrossRefGoogle Scholar
  50. 50.
    James CD, Carlbom E, Dumanskji JP, et al: Clonal genomic alterations in glioma malignancy stages. Cancer Res 1988; 48: 5546–5551PubMedGoogle Scholar
  51. 51.
    Boyle P, Leake R: Progress in understanding breast cancer: Epidemiological and biological interactions. Breast Cancer Res Treat 1988; 11: 91–112PubMedCrossRefGoogle Scholar
  52. 52.
    Harris JR, Lippman ME, Veronesi U, Willett W: Breast cancer. N Engl J Med 1992; 327: 319–328, 390–398,473–480PubMedCrossRefGoogle Scholar
  53. 53.
    Carney DN: Biology of small cell lung cancer. Lancet 1992; 339: 843–846PubMedCrossRefGoogle Scholar
  54. 54.
    Correa P: Biochemical and molecular methods in cancer epidemiology and prevention: the path between the laboratory and the population. Cancer Epidem Biomark Prev 1993; 2:85–88Google Scholar
  55. 55.
    Vineis P: Epidemiological models of carcinogenesis: the example of bladder cancer. Cancer Epidem Biomark Prev 1992; 1:149–154Google Scholar
  56. 56.
    el Azouzi M, Chung RY, Farmer GE, et al: Lost of distinct regions on the short arm of chromosome 17 associated with tumorigenesis of human astrocytomas. Proc Natl Acad Sci USA 1989; 86: 7186–7190PubMedCrossRefGoogle Scholar
  57. 57.
    Linehan WM, Gnarra JR, Lerman MI, et al: Genetic bases of renal cell cancer. In: DeVita VT; Hellman S.; Rosenberg S.A.: Important Advances in Oncology, 1993. J.B. Lippincott, 1993,47–70Google Scholar
  58. 58.
    Franco EL: Prognostic value of human papillomavirus in the survival of cervical cancer patients: an overview of the evidence. Cancer Epidemiol Biomark Prev 1992; 1: 499–504Google Scholar
  59. 59.
    Anisimov VN: Age as a factor of risk in multistage carcinogenesis. In Balducci L, Lyman GH, Ershler WB, eds: Geriatric Oncology, J.B. Lippincott, 1992, 53–60Google Scholar
  60. 60.
    Fernandez-Pol JA: Growth factors, oncogenes, antioncogenes and aging. In Balducci L, Lyman GH, Ershler WB, eds: Comprehensive Geriatric Oncology, Harcourt, 1998, 179–196Google Scholar
  61. 61.
    Stevens RG, Jones DY, Micozzi MS, Taylor PR: Body iron stores and the risk of cancer. N Engl J Med 1988; 319: 1047–1052PubMedCrossRefGoogle Scholar
  62. 62.
    Anisimov VN: Effect of age on dose-response relationship in carcinogenesis induced by single administration of N-methynitrosourea in female rats. J Cancer Res Clin Oncol 1988; 114: 628–635PubMedCrossRefGoogle Scholar
  63. 63.
    Ward JM, Lynch P, Riggs C: Rapid development of hepatocellular neoplasms in aging male C3H/HeNcr mice given phenobarbital. Cancer Lett 1988; 39:9–18PubMedCrossRefGoogle Scholar
  64. 64.
    Ebbesen P: Reticulosarcoma and amyloid development in BALB/c mice inoculated with syngeneic cells from young and old donors. J Natl Cancer Inst 1971; 47: 1241–1245PubMedGoogle Scholar
  65. 65.
    Anisimov VN, Loktionov AS, Khavinson VK, Morozov VG: Effect of low molecular weight factors of thymus and pineal gland on life span and spontaneous tumor development in female mice of different age. Mech Ageing Dev 1989; 49: 245–257PubMedCrossRefGoogle Scholar
  66. 66.
    Kaldor JM, Day NE: Interpretation of epidemiological studies in the context of the multistage model of carcinogenesis. In Barrett JC: Mechanisms of Environmental Carcinogenesis, Vol 2, CRC press, 1987, 21–57Google Scholar
  67. 67.
    Tantranond P, Karam F, Wang TY, et al: Management of cutaneous squamous cell carcinoma in an elderly man. J Am Ger Soc 1992; 40: 510–512Google Scholar
  68. 68.
    Glass AG, Hoover RN: The emerging epidemic of melanoma and squamous cell carcinoma of the skin. JAMA 1989; 262: 2097–2100PubMedCrossRefGoogle Scholar
  69. 69.
    Matoha MF, Cosgrove JW, Atak JR, Rappoport SI: Selective elevation of the c-myc transcript levels in the liver of the aging Fischer 344 rat. Biochem Biophys Res Commun 1987; 147:1–7CrossRefGoogle Scholar
  70. 70.
    Bohr VA, Evans MK, Fornace AJ: Biology of disease: DNA repair and its patogenetic implications. Lab Invest 1989; 61:143–161PubMedGoogle Scholar
  71. 71.
    Randerath K, Reddy MV, Disher RM: Age-and tissue-related DNA modifications in untreated rats: Detection by 32P-post-labeling assay and possible significance for spontaneous tumor induction and aging. Carcinogenesis 1986; 7:1615–1617PubMedGoogle Scholar
  72. 72.
    Ershler WB, Stewart JA, Hacker MP, Moore AL, Tindle BH: B16 murine melanoma and aging: Slower growth and longer survival in old mice, JNCI 1984; 72:161–165PubMedGoogle Scholar
  73. 73.
    Ershler WB, Moore AL, Shore H, Gamelli RL: Transfer of age-associated restrained tumor growth in mice by old to young bone marrow transplantation. Cancer Research 1984; 44:5677–81PubMedGoogle Scholar
  74. 74.
    Tsuda T, Kim YT, Siskind GW, DeBlasio A, Schwab R, Ershler WB, Weksler ME: Role of the thymus and T-cells in slow growth of B16 melanoma in old mice. Cancer Research 1987; 47:3097–3103PubMedGoogle Scholar
  75. 75.
    Ershler WB, Guest Editorial: Why tumors grow more slowly in old people. JNCI 77 1986;837–839Google Scholar
  76. 76.
    Simon SR, Ershler WB: Hormonal influences on growth of B16 murine melanoma. JNCI 1985; 74:1085–1088PubMedGoogle Scholar
  77. 77.
    Ershler WB, Berman E, Moore AL: B16 melanoma growth is slower, but pulmonary colonization is greater in calorie restricted mice. J Natl Cancer Inst 1986; 76:81–5PubMedGoogle Scholar
  78. 78.
    Ershler WB, Gamelli RL, Moore AL, Hacker MP, and Blow AJ: Experimental tumors and aging: Local factors that may account for the observed age advantage in the B16 murine melanoma model. Exp Gerontol 1984 19:367–375PubMedCrossRefGoogle Scholar
  79. 79.
    Hadar E, Ershler WB, Kreisle R.A, Ho S-P, Volk MJ, Klopp RG: Lymphocyte-induced angiogenesis factor is produced by L3T4+ murine T lymphocytes, and its production declines with age. Cancer Immunol. Immunother 1988; 26:31–37PubMedCrossRefGoogle Scholar
  80. 80.
    Kreisle RA, Stebler B, Ershler WB: Effect of host age on tumor associated angiogenesis in mice. JNCI 1990; 82:44–47PubMedGoogle Scholar
  81. 81.
    Fidler IJ, Gersten DM, Riggs CW: Relationship of host immune status to tumor cell arrest, distribution and survival in experimental metastases. Cancer 1977 40:46–55PubMedGoogle Scholar
  82. 82.
    Prehn RT, Lappe, MA: An immunostimulation theory of tumor development. Transplant Rev 1971; 7:26–30PubMedGoogle Scholar

Copyright information

© Springer Science + Business Media, Inc. 2005

Authors and Affiliations

  • William B. Ershler
    • 1
  1. 1.Institute for Advanced Studies in Aging & Geriatric MedicineWashington, DC

Personalised recommendations