Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Opinion
  • Published:

How ageing processes influence cancer

Nature Reviews Cancer volume 13, pages 357–365 (2013)Cite this article

Subjects

Abstract

The ageing of populations worldwide is leading to an unprecedented increase in cancer cases and fatalities. Understanding the links between cancer and ageing is therefore more important than ever. How the interplay of ageing-associated changes affects cancer initiation and progression is complex, however, and some ageing processes probably foster cancer development whereas others hinder it, possibly in a tissue-specific manner. In the emerging age of cancer, how can our growing understanding of the biology of ageing inform cancer biology?

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: The incidence of cancer diagnosis as a function of age.
Figure 2: Major longevity pathways with overlapping effects on ageing and cancer.
Figure 3: Cancer survival as a function of age.
Figure 4: The interplay between ageing processes and cancer.

Similar content being viewed by others

References

  1. Peto, J. Cancer epidemiology in the last century and the next decade. Nature 411, 390–395 (2001).

    Article  CAS  PubMed  Google Scholar 

  2. Edwards, B. K. et al. Annual report to the nation on the status of cancer, 1973–1999, featuring implications of age and aging on U.S. cancer burden. Cancer 94, 2766–2792 (2002).

    Article  PubMed  Google Scholar 

  3. Parkin, D. M., Bray, F. I. & Devesa, S. S. Cancer burden in the year 2000. The global picture. Eur. J. Cancer 37 (Suppl. 8), S4–S66 (2001).

    Article  PubMed  Google Scholar 

  4. Frank, S. A. Dynamics of Cancer: Incidence, Inheritance, and Evolution (Princeton (NJ), 2007).

    Google Scholar 

  5. Jones, D. S., Podolsky, S. H. & Greene, J. A. The burden of disease and the changing task of medicine. N. Engl. J. Med. 366, 2333–2338 (2012).

    Article  CAS  PubMed  Google Scholar 

  6. Balducci, L. & Ershler, W. B. Cancer and ageing: a nexus at several levels. Nature Rev. Cancer 5, 655–662 (2005).

    Article  CAS  Google Scholar 

  7. Peto, R. & Doll, R. There is no such thing as aging. BMJ 315, 1030–1032 (1997).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Christensen, K. et al. Cancer and longevity—is there a trade-off? A study of cooccurrence in Danish twin pairs born 1900–1918. J. Gerontol. A Biol. Sci. Med. Sci. 67, 489–494 (2012).

    Article  PubMed  Google Scholar 

  9. Anisimov, V. N. Carcinogenesis and aging 20 years after: escaping horizon. Mech. Ageing Dev. 130, 105–121 (2009).

    Article  CAS  PubMed  Google Scholar 

  10. de Magalhaes, J. P., Wuttke, D., Wood, S. H., Plank, M. & Vora, C. Genome-environment interactions that modulate aging: powerful targets for drug discovery. Pharmacol. Rev. 64, 88–101 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Baker, D. J. et al. Increased expression of BubR1 protects against aneuploidy and cancer and extends healthy lifespan. Nature Cell Biol. 15, 96–102 (2013).

    Article  CAS  PubMed  Google Scholar 

  12. Anisimov, V. N. The relationship between aging and carcinogenesis: a critical appraisal. Crit. Rev. Oncol. Hematol. 45, 277–304 (2003).

    Article  PubMed  Google Scholar 

  13. Stanta, G., Campagner, L., Cavallieri, F. & Giarelli, L. Cancer of the oldest old. What we have learned from autopsy studies. Clin. Geriatr. Med. 13, 55–68 (1997).

    Article  CAS  PubMed  Google Scholar 

  14. Vaupel, J. W. Biodemography of human ageing. Nature 464, 536–542 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. de Magalhaes, J. P. in An Introduction to Gerontology (ed. Stuart-Hamilton, I.) 21–47 (Cambridge Univ. Press, 2011).

  16. Kenyon, C. J. The genetics of ageing. Nature 464, 504–512 (2010).

    Article  CAS  PubMed  Google Scholar 

  17. Tacutu, R. et al. Human Ageing Genomic Resources: integrated databases and tools for the biology and genetics of ageing. Nucleic Acids Res. 41, D1027–D1033 (2013).

    Article  CAS  PubMed  Google Scholar 

  18. Matheu, A. et al. Delayed ageing through damage protection by the Arf/p53 pathway. Nature 448, 375–379 (2007).

    Article  CAS  PubMed  Google Scholar 

  19. Ikeno, Y. et al. Reduced incidence and delayed occurrence of fatal neoplastic diseases in growth hormone receptor/binding protein knockout mice. J. Gerontol. A Biol. Sci. Med. Sci. 64, 522–529 (2009).

    Article  PubMed  CAS  Google Scholar 

  20. Ikeno, Y., Bronson, R. T., Hubbard, G. B., Lee, S. & Bartke, A. Delayed occurrence of fatal neoplastic diseases in Ames dwarf mice: correlation to extended longevity. J. Gerontol. A Biol. Sci. Med. Sci. 58, 291–296 (2003).

    Article  PubMed  Google Scholar 

  21. Ng, S. T. et al. Growth hormone treatment induces mammary gland hyperplasia in aging primates. Nature Med. 3, 1141–1144 (1997).

    Article  CAS  PubMed  Google Scholar 

  22. de Magalhaes, J. P. & Faragher, R. G. Cell divisions and mammalian aging: integrative biology insights from genes that regulate longevity. Bioessays 30, 567–578 (2008).

    Article  CAS  PubMed  Google Scholar 

  23. Guevara-Aguirre, J. et al. Growth hormone receptor deficiency is associated with a major reduction in pro-aging signaling, cancer, and diabetes in humans. Sci. Transl Med. 3, 70ra13 (2011).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  24. Coschigano, K. T. et al. Deletion, but not antagonism, of the mouse growth hormone receptor results in severely decreased body weights, insulin, and insulin-like growth factor I levels and increased life span. Endocrinology 144, 3799–3810 (2003).

    Article  CAS  PubMed  Google Scholar 

  25. Gunnell, D. et al. Height, leg length, and cancer risk: a systematic review. Epidemiol. Rev. 23, 313–342 (2001).

    Article  CAS  PubMed  Google Scholar 

  26. Freitas, A. A. & de Magalhaes, J. P. A review and appraisal of the DNA damage theory of ageing. Mutat. Res. 728, 12–22 (2011).

    Article  CAS  PubMed  Google Scholar 

  27. Goto, M., Miller, R. W., Ishikawa, Y. & Sugano, H. Excess of rare cancers in Werner syndrome (adult progeria). Cancer Epidemiol. Biomarkers Prev. 5, 239–246 (1996).

    CAS  PubMed  Google Scholar 

  28. Hoeijmakers, J. H. DNA damage, aging, and cancer. N. Engl. J. Med. 361, 1475–1485 (2009).

    Article  CAS  PubMed  Google Scholar 

  29. Lombard, D. B. et al. DNA repair, genome stability, and aging. Cell 120, 497–512 (2005).

    Article  CAS  PubMed  Google Scholar 

  30. Freitas, A. A., Vasieva, O. & de Magalhaes, J. P. A data mining approach for classifying DNA repair genes into ageing-related or non-ageing-related. BMC Genomics 12, 27 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Hursting, S. D., Lavigne, J. A., Berrigan, D., Perkins, S. N. & Barrett, J. C. Calorie restriction, aging, and cancer prevention: mechanisms of action and applicability to humans. Annu. Rev. Med. 54, 131–152 (2003).

    Article  CAS  PubMed  Google Scholar 

  32. Harper, J. M., Leathers, C. W. & Austad, S. N. Does caloric restriction extend life in wild mice? Aging Cell 5, 441–449 (2006).

    Article  CAS  PubMed  Google Scholar 

  33. Weindruch, R. & Walford, R. L. Dietary restriction in mice beginning at 1 year of age: effect on life-span and spontaneous cancer incidence. Science 215, 1415–1418 (1982).

    Article  CAS  PubMed  Google Scholar 

  34. Pugh, T. D., Oberley, T. D. & Weindruch, R. Dietary intervention at middle age: caloric restriction but not dehydroepiandrosterone sulfate increases lifespan and lifetime cancer incidence in mice. Cancer Res. 59, 1642–1648 (1999).

    CAS  PubMed  Google Scholar 

  35. Dhahbi, J. M., Kim, H. J., Mote, P. L., Beaver, R. J. & Spindler, S. R. Temporal linkage between the phenotypic and genomic responses to caloric restriction. Proc. Natl Acad. Sci. USA 101, 5524–5529 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Colman, R. J. et al. Caloric restriction delays disease onset and mortality in rhesus monkeys. Science 325, 201–204 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Mattison, J. A. et al. Impact of caloric restriction on health and survival in rhesus monkeys from the NIA study. Nature 489, 318–321 (2012).

    Article  CAS  PubMed  Google Scholar 

  38. Calle, E. E. & Kaaks, R. Overweight, obesity and cancer: epidemiological evidence and proposed mechanisms. Nature Rev. Cancer 4, 579–591 (2004).

    Article  CAS  Google Scholar 

  39. Longo, V. D. & Fontana, L. Calorie restriction and cancer prevention: metabolic and molecular mechanisms. Trends Pharmacol. Sci. 31, 89–98 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Flegal, K. M., Graubard, B. I., Williamson, D. F. & Gail, M. H. Cause-specific excess deaths associated with underweight, overweight, and obesity. JAMA 298, 2028–2037 (2007).

    Article  CAS  PubMed  Google Scholar 

  41. Liao, C. Y. et al. Fat maintenance is a predictor of the murine lifespan response to dietary restriction. Aging Cell 10, 629–639 (2011).

    Article  CAS  PubMed  Google Scholar 

  42. Breese, C. R., Ingram, R. L. & Sonntag, W. E. Influence of age and long-term dietary restriction on plasma insulin-like growth factor-1 (IGF-1), IGF-1 gene expression, and IGF-1 binding proteins. J. Gerontol. 46, B180–B187 (1991).

    Article  CAS  PubMed  Google Scholar 

  43. Grimberg, A. & Cohen, P. Role of insulin-like growth factors and their binding proteins in growth control and carcinogenesis. J. Cell. Physiol. 183, 1–9 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Dunn, S. E. et al. Dietary restriction reduces insulin-like growth factor I levels, which modulates apoptosis, cell proliferation, and tumor progression in p53-deficient mice. Cancer Res. 57, 4667–4672 (1997).

    CAS  PubMed  Google Scholar 

  45. Herranz, D. & Serrano, M. SIRT1: recent lessons from mouse models. Nature Rev. Cancer 10, 819–823 (2010).

    Article  CAS  Google Scholar 

  46. Herranz, D. et al. Sirt1 improves healthy ageing and protects from metabolic syndrome-associated cancer. Nature. Commun. 1, 3 (2010).

    Article  CAS  Google Scholar 

  47. Fresno Vara, J. A. et al. PI3K/Akt signalling pathway and cancer. Cancer Treat. Rev. 30, 193–204 (2004).

    Article  PubMed  CAS  Google Scholar 

  48. Vijg, J. & Dolle, M. E. Large genome rearrangements as a primary cause of aging. Mech. Ageing Dev. 123, 907–915 (2002).

    Article  CAS  PubMed  Google Scholar 

  49. Jacobs, K. B. et al. Detectable clonal mosaicism and its relationship to aging and cancer. Nature Genet. 44, 651–658 (2012).

    Article  CAS  PubMed  Google Scholar 

  50. Laurie, C. C. et al. Detectable clonal mosaicism from birth to old age and its relationship to cancer. Nature Genet. 44, 642–650 (2012).

    Article  CAS  PubMed  Google Scholar 

  51. Stuart, G. R., Oda, Y., de Boer, J. G. & Glickman, B. W. Mutation frequency and specificity with age in liver, bladder and brain of lacI transgenic mice. Genetics 154, 1291–1300 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  52. Dolle, M. E. et al. Rapid accumulation of genome rearrangements in liver but not in brain of old mice. Nature Genet. 17, 431–434 (1997).

    Article  CAS  PubMed  Google Scholar 

  53. Dolle, M. E., Snyder, W. K., Gossen, J. A., Lohman, P. H. & Vijg, J. Distinct spectra of somatic mutations accumulated with age in mouse heart and small intestine. Proc. Natl Acad. Sci. USA 97, 8403–8408 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Busuttil, R. A. et al. Intra-organ variation in age-related mutation accumulation in the mouse. PLoS ONE 2, e876 (2007).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  55. Johnson, A. A. et al. The role of DNA methylation in aging, rejuvenation, and age-related disease. Rejuven. Res. 15, 483–494 (2012).

    CAS  Google Scholar 

  56. Peters, I. et al. Adiposity and age are statistically related to enhanced RASSF1A tumor suppressor gene promoter methylation in normal autopsy kidney tissue. Cancer Epidemiol. Biomarkers Prev. 16, 2526–2532 (2007).

    Article  CAS  PubMed  Google Scholar 

  57. Gorbunova, V., Seluanov, A., Mao, Z. & Hine, C. Changes in DNA repair during aging. Nucleic Acids Res. 35, 7466–7474 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Anisimov, V. N. Effect of age on dose-response relationship in carcinogenesis induced by single administration of N-nitrosomethylurea in female rats. J. Cancer Res. Clin. Oncol. 114, 628–635 (1988).

    Article  CAS  PubMed  Google Scholar 

  59. Collado, M., Blasco, M. A. & Serrano, M. Cellular senescence in cancer and aging. Cell 130, 223–233 (2007).

    Article  CAS  PubMed  Google Scholar 

  60. Campisi, J. Senescent cells, tumor suppression, and organismal aging: good citizens, bad neighbors. Cell 120, 513–522 (2005).

    Article  CAS  PubMed  Google Scholar 

  61. de Magalhaes, J. P. From cells to ageing: a review of models and mechanisms of cellular senescence and their impact on human ageing. Exp. Cell Res. 300, 1–10 (2004).

    Article  PubMed  CAS  Google Scholar 

  62. Finkel, T., Serrano, M. & Blasco, M. A. The common biology of cancer and ageing. Nature 448, 767–774 (2007).

    Article  CAS  PubMed  Google Scholar 

  63. Gomes, N. M. et al. Comparative biology of mammalian telomeres: hypotheses on ancestral states and the roles of telomeres in longevity determination. Aging Cell 10, 761–768 (2011).

    Article  CAS  PubMed  Google Scholar 

  64. Minamino, T. et al. Endothelial cell senescence in human atherosclerosis: role of telomere in endothelial dysfunction. Circulation 105, 1541–1544 (2002).

    Article  CAS  PubMed  Google Scholar 

  65. Castro, P., Giri, D., Lamb, D. & Ittmann, M. Cellular senescence in the pathogenesis of benign prostatic hyperplasia. Prostate 55, 30–38 (2003).

    Article  CAS  PubMed  Google Scholar 

  66. Herbig, U., Ferreira, M., Condel, L., Carey, D. & Sedivy, J. M. Cellular senescence in aging primates. Science 311, 1257 (2006).

    Article  CAS  PubMed  Google Scholar 

  67. Panda, S., Isbatan, A. & Adami, G. R. Modification of the ATM/ATR directed DNA damage response state with aging and long after hepatocyte senescence induction in vivo. Mech. Ageing Dev. 129, 332–340 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Wang, C. et al. DNA damage response and cellular senescence in tissues of aging mice. Aging Cell 8, 311–323 (2009).

    Article  CAS  PubMed  Google Scholar 

  69. Molofsky, A. V. et al. Increasing p16INK4a expression decreases forebrain progenitors and neurogenesis during ageing. Nature 443, 448–452 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Krishnamurthy, J. et al. p16INK4a induces an age-dependent decline in islet regenerative potential. Nature 443, 453–457 (2006).

    Article  CAS  PubMed  Google Scholar 

  71. DePinho, R. A. The age of cancer. Nature 408, 248–254 (2000).

    Article  CAS  PubMed  Google Scholar 

  72. Rudolph, K. L. et al. Longevity, stress response, and cancer in aging telomerase-deficient mice. Cell 96, 701–712 (1999).

    Article  CAS  PubMed  Google Scholar 

  73. Chin, L. et al. p53 deficiency rescues the adverse effects of telomere loss and cooperates with telomere dysfunction to accelerate carcinogenesis. Cell 97, 527–538 (1999).

    Article  CAS  PubMed  Google Scholar 

  74. Krtolica, A., Parrinello, S., Lockett, S., Desprez, P. Y. & Campisi, J. Senescent fibroblasts promote epithelial cell growth and tumorigenesis: a link between cancer and aging. Proc. Natl Acad. Sci. USA 98, 12072–12077 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Coppe, J. P. et al. A human-like senescence-associated secretory phenotype is conserved in mouse cells dependent on physiological oxygen. PLoS ONE 5, e9188 (2010).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  76. Liu, D. & Hornsby, P. J. Senescent human fibroblasts increase the early growth of xenograft tumors via matrix metalloproteinase secretion. Cancer Res. 67, 3117–3126 (2007).

    Article  CAS  PubMed  Google Scholar 

  77. Burd, C. E. et al. Monitoring tumorigenesis and senescence in vivo with a p16INK4a-luciferase model. Cell 152, 340–351 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Baker, D. J. et al. Clearance of p16Ink4a-positive senescent cells delays ageing-associated disorders. Nature 479, 232–236 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Folkerd, E. J. & Dowsett, M. Influence of sex hormones on cancer progression. J. Clin. Oncol. 28, 4038–4044 (2010).

    Article  CAS  PubMed  Google Scholar 

  80. Ho, K. Y. et al. Effects of sex and age on the 24-hour profile of growth hormone secretion in man: importance of endogenous estradiol concentrations. J. Clin. Endocrinol. Metab. 64, 51–58 (1987).

    Article  CAS  PubMed  Google Scholar 

  81. Hammerman, M. R. Insulin-like growth factors and aging. Endocrinol. Metab. Clin. North Am. 16, 995–1011 (1987).

    Article  CAS  PubMed  Google Scholar 

  82. Miller, R. A. The aging immune system: primer and prospectus. Science 273, 70–74 (1996).

    Article  CAS  PubMed  Google Scholar 

  83. Franceschi, C. et al. Inflammaging and anti-inflammaging: a systemic perspective on aging and longevity emerged from studies in humans. Mech. Ageing Dev. 128, 92–105 (2007).

    Article  CAS  PubMed  Google Scholar 

  84. Fagiolo, U. et al. Increased cytokine production in mononuclear cells of healthy elderly people. Eur. J. Immunol. 23, 2375–2378 (1993).

    Article  CAS  PubMed  Google Scholar 

  85. Kaesberg, P. R. & Ershler, W. B. The importance of immunesenescence in the incidence and malignant properties of cancer in hosts of advanced age. J. Gerontol. 44, 63–66 (1989).

    Article  CAS  PubMed  Google Scholar 

  86. Ershler, W. B. & Longo, D. L. Aging and cancer: issues of basic and clinical science. J. Natl Cancer Inst. 89, 1489–1497 (1997).

    Article  CAS  PubMed  Google Scholar 

  87. Swann, J. B. & Smyth, M. J. Immune surveillance of tumors. J. Clin. Invest. 117, 1137–1146 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Mantovani, A., Allavena, P., Sica, A. & Balkwill, F. Cancer-related inflammation. Nature 454, 436–444 (2008).

    Article  CAS  PubMed  Google Scholar 

  89. Colotta, F., Allavena, P., Sica, A., Garlanda, C. & Mantovani, A. Cancer-related inflammation, the seventh hallmark of cancer: links to genetic instability. Carcinogenesis 30, 1073–1081 (2009).

    Article  CAS  PubMed  Google Scholar 

  90. Pedersen, M. et al. Circulating levels of TNFα and IL-6-relation to truncal fat mass and muscle mass in healthy elderly individuals and in patients with type-2 diabetes. Mech. Ageing Dev. 124, 495–502 (2003).

    Article  CAS  PubMed  Google Scholar 

  91. de Magalhaes, J. P., Curado, J. & Church, G. M. Meta-analysis of age-related gene expression profiles identifies common signatures of aging. Bioinformatics 25, 875–881 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Kim, S. et al. Circulating levels of inflammatory cytokines and risk of colorectal adenomas. Cancer Res. 68, 323–328 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Fontana, L., Eagon, J. C., Trujillo, M. E., Scherer, P. E. & Klein, S. Visceral fat adipokine secretion is associated with systemic inflammation in obese humans. Diabetes 56, 1010–1013 (2007).

    Article  CAS  PubMed  Google Scholar 

  94. Durnin, J. V. & Womersley, J. Body fat assessed from total body density and its estimation from skinfold thickness: measurements on 481 men and women aged from 16 to 72 years. Br. J. Nutr. 32, 77–97 (1974).

    Article  CAS  PubMed  Google Scholar 

  95. Pili, R. et al. Altered angiogenesis underlying age-dependent changes in tumor growth. J. Natl Cancer Inst. 86, 1303–1314 (1994).

    Article  CAS  PubMed  Google Scholar 

  96. Klement, H. et al. Atherosclerosis and vascular aging as modifiers of tumor progression, angiogenesis, and responsiveness to therapy. Am. J. Pathol. 171, 1342–1351 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Franco, S., Segura, I., Riese, H. H. & Blasco, M. A. Decreased B16F10 melanoma growth and impaired vascularization in telomerase-deficient mice with critically short telomeres. Cancer Res. 62, 552–559 (2002).

    CAS  PubMed  Google Scholar 

  98. Hinkal, G., Parikh, N. & Donehower, L. A. Timed somatic deletion of p53 in mice reveals age-associated differences in tumor progression. PLoS ONE 4, e6654 (2009).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  99. Peto, R., Roe, F. J., Lee, P. N., Levy, L. & Clack, J. Cancer and ageing in mice and men. Br. J. Cancer 32, 411–426 (1975).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Anisimov, V. N. Effect of host age on tumor growth rate in rodents. Front. Biosci. 11, 412–422 (2006).

    Article  CAS  PubMed  Google Scholar 

  101. Reed, M. J. et al. The effects of aging on tumor growth and angiogenesis are tumor-cell dependent. Int. J. Cancer 120, 753–760 (2007).

    Article  CAS  PubMed  Google Scholar 

  102. Ershler, W. B., Stewart, J. A., Hacker, M. P., Moore, A. L. & Tindle, B. H. B16 murine melanoma and aging: slower growth and longer survival in old mice. J. Natl Cancer Inst. 72, 161–164 (1984).

    Article  CAS  PubMed  Google Scholar 

  103. McCullough, K. D., Coleman, W. B., Smith, G. J. & Grisham, J. W. Age-dependent induction of hepatic tumor regression by the tissue microenvironment after transplantation of neoplastically transformed rat liver epithelial cells into the liver. Cancer Res. 57, 1807–1813 (1997).

    CAS  PubMed  Google Scholar 

  104. Lancet, J. E., Willman, C. L. & Bennett, J. M. Acute myelogenous leukemia and aging. Clinical interactions. Hematol. Oncol. Clin. North Am. 14, 251–267 (2000).

    Article  CAS  PubMed  Google Scholar 

  105. Maas, H. A., Kruitwagen, R. F., Lemmens, V. E., Goey, S. H. & Janssen-Heijnen, M. L. The influence of age and co-morbidity on treatment and prognosis of ovarian cancer: a population-based study. Gynecol. Oncol. 97, 104–109 (2005).

    Article  CAS  PubMed  Google Scholar 

  106. Adami, H. O., Malker, B., Holmberg, L., Persson, I. & Stone, B. The relation between survival and age at diagnosis in breast cancer. N. Engl. J. Med. 315, 559–563 (1986).

    Article  CAS  PubMed  Google Scholar 

  107. Michels, K. B. & Ekbom, A. Caloric restriction and incidence of breast cancer. JAMA 291, 1226–1230 (2004).

    Article  CAS  PubMed  Google Scholar 

  108. Lee, C. et al. Reduced levels of IGF-I mediate differential protection of normal and cancer cells in response to fasting and improve chemotherapeutic index. Cancer Res. 70, 1564–1572 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  109. Safdie, F. M. et al. Fasting and cancer treatment in humans: A case series report. Aging 1, 988–1007 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  110. Firestein, R. et al. The SIRT1 deacetylase suppresses intestinal tumorigenesis and colon cancer growth. PLoS ONE 3, e2020 (2008).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  111. Wang, R. H. et al. Interplay among BRCA1, SIRT1, and Survivin during BRCA1-associated tumorigenesis. Mol. Cell 32, 11–20 (2008).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  112. Lara, E. et al. Salermide, a Sirtuin inhibitor with a strong cancer-specific proapoptotic effect. Oncogene 28, 781–791 (2009).

    Article  CAS  PubMed  Google Scholar 

  113. Li, L. et al. Activation of p53 by SIRT1 inhibition enhances elimination of CML leukemia stem cells in combination with imatinib. Cancer Cell 21, 266–281 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  114. Brooks, C. L. & Gu, W. How does SIRT1 affect metabolism, senescence and cancer? Nature Rev. Cancer 9, 123–128 (2009).

    Article  CAS  Google Scholar 

  115. Harrison, D. E. et al. Rapamycin fed late in life extends lifespan in genetically heterogeneous mice. Nature 460, 392–395 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  116. Komarova, E. A. et al. Rapamycin extends lifespan and delays tumorigenesis in heterozygous p53+/− mice. Aging 4, 709–714 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  117. Zakikhani, M., Dowling, R., Fantus, I. G., Sonenberg, N. & Pollak, M. Metformin is an AMP kinase-dependent growth inhibitor for breast cancer cells. Cancer Res. 66, 10269–10273 (2006).

    Article  CAS  PubMed  Google Scholar 

  118. Kalender, A. et al. Metformin, independent of AMPK, inhibits mTORC1 in a rag GTPase-dependent manner. Cell. Metab. 11, 390–401 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  119. Libby, G. et al. New users of metformin are at low risk of incident cancer: a cohort study among people with type 2 diabetes. Diabetes Care 32, 1620–1625 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  120. Strong, R. et al. Nordihydroguaiaretic acid and aspirin increase lifespan of genetically heterogeneous male mice. Aging Cell 7, 641–650 (2008).

    Article  CAS  PubMed  Google Scholar 

  121. Algra, A. M. & Rothwell, P. M. Effects of regular aspirin on long-term cancer incidence and metastasis: a systematic comparison of evidence from observational studies versus randomised trials. Lancet Oncol. 13, 518–527 (2012).

    Article  CAS  PubMed  Google Scholar 

  122. Rothwell, P. M. et al. Short-term effects of daily aspirin on cancer incidence, mortality, and non-vascular death: analysis of the time course of risks and benefits in 51 randomised controlled trials. Lancet 379, 1602–1612 (2012).

    Article  CAS  PubMed  Google Scholar 

  123. Dowling, R. J., Goodwin, P. J. & Stambolic, V. Understanding the benefit of metformin use in cancer treatment. BMC Med. 9, 33 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  124. Buffenstein, R. Negligible senescence in the longest living rodent, the naked mole-rat: insights from a successfully aging species. J. Comp. Physiol. B 178, 439–445 (2008).

    Article  PubMed  Google Scholar 

  125. Caulin, A. F. & Maley, C. C. Peto's Paradox: evolution's prescription for cancer prevention. Trends Ecol. Evol. 26, 175–182 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  126. Buffenstein, R. The naked mole-rat: a new long-living model for human aging research. J. Gerontol. A Biol. Sci. Med. Sci. 60, 1369–1377 (2005).

    Article  PubMed  Google Scholar 

  127. Seluanov, A. et al. Distinct tumor suppressor mechanisms evolve in rodent species that differ in size and lifespan. Aging Cell 7, 813–823 (2008).

    Article  CAS  PubMed  Google Scholar 

  128. Seluanov, A. et al. Hypersensitivity to contact inhibition provides a clue to cancer resistance of naked mole-rat. Proc. Natl Acad. Sci. USA 106, 19352–19357 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  129. Liang, S., Mele, J., Wu, Y., Buffenstein, R. & Hornsby, P. J. Resistance to experimental tumorigenesis in cells of a long-lived mammal, the naked mole-rat (Heterocephalus glaber). Aging Cell 9, 626–635 (2010).

    Article  CAS  PubMed  Google Scholar 

  130. Gorbunova, V. et al. Cancer resistance in the blind mole rat is mediated by concerted necrotic cell death mechanism. Proc. Natl Acad. Sci. USA 109, 19392–19396 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  131. George, J. C. et al. Age and growth estimates of bowhead whales (Balaena mysticetus) via aspartic acid racemization. Can. J. Zool. 77, 571–580 (1999).

    Article  Google Scholar 

  132. Li, Y. & de Magalhaes, J. P. Accelerated protein evolution analysis reveals genes and pathways associated with the evolution of mammalian longevity. Age 35, 301–314 (2013).

    Article  CAS  PubMed  Google Scholar 

  133. United States Department of Health and Human Services, Centers for Disease Control and Prevention and National Cancer Institute. United States Cancer Statistics: 1999–2009 WONDER Online Database [online] (2013).

Download references

Acknowledgements

I thank everyone at the Lifestyle and Ageing Multidisciplinary Conference in Pisa, Italy, October 2010, for discussions that spurred this work and all participants at the European Science Foundation (ESF) Exploratory Workshop on Physics of Cancer in Varenna, Italy, September 2012, for fruitful discussions on these topics. Further thanks to J. Costa and to members of my laboratory, in particular S. Wood, D. Wuttke and R. Tacutu, for useful comments and suggestions. I am also grateful for support from the UK Biotechnology and Biological Sciences Research Council (BBSRC), the Wellcome Trust, the Royal Society, the Ellison Medical Foundation and from a Marie Curie International Reintegration Grant within EC-FP7 for supporting the work in my laboratory. I apologize to those whose work I could not cite owing to space limitations.

Author information

Authors and Affiliations

  1. João Pedro de Magalhães is in the Integrative Genomics of Ageing Group, Institute of Integrative Biology, University of Liverpool, Liverpool, UK. jp@senescence.info,

    João Pedro de Magalhães

Authors
  1. João Pedro de Magalhães
    View author publications

    You can also search for this author in PubMed Google Scholar

Ethics declarations

Competing interests

The author declares no competing financial interests.

Related links

Rights and permissions

Reprints and permissions

About this article

Cite this article

de Magalhães, J. How ageing processes influence cancer. Nat Rev Cancer 13, 357–365 (2013). https://doi.org/10.1038/nrc3497

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrc3497

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing