Skip to main content
SpringerLink
Log in

Relationships between cancer and aging: a multilevel approach

  • Review Article
  • Published:
Biogerontology Aims and scope Submit manuscript

Abstract

The incidence of cancer increases with age in humans and in laboratory animals alike. There are different patterns of age-related distribution of tumors in different organs and tissues. Aging may increase or decrease the susceptibility of various tissues to initiation of carcinogenesis and usually facilitates promotion and progression of carcinogenesis. Aging may predispose to cancer in two ways: tissue accumulation of cells in late stages of carcinogenesis and alterations in internal homeostasis, in particular, alterations in immune and endocrine systems. Increased susceptibility to the effects of tumor promoters is found both in aged animals and aged humans, as predicted by the multistage model of carcinogenesis. Aging is associated with a number of events at the molecular, cellular and physiological levels that influence carcinogenesis and subsequent cancer growth. An improved understanding of age-associated variables impacting on the tumor microenvironment, as well as the cancer cells themselves, will result in improved treatment modalities in geriatric oncology.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  • Alexandrov VA, Anisimov VN, Belous NM et al (1980) The inhibition of the transplacental blastomogenic effect of nitrosomethylurea by postnatal administration of buformin to rats. Carcinogenesis 1:975–978

    PubMed  CAS  Google Scholar 

  • Anisimov VN (1983) Carcinogenesis and aging. Adv Cancer Res 40:265–324

    Google Scholar 

  • Anisimov VN (1987) Carcinogenesis and aging, vol 1 and 2. CRC, Boca Raton

    Google Scholar 

  • Anisimov VN (1994) The sole DNA damage induced by bromodeoxyuridine is sufficient for initiation of both aging and carcinogenesis in vivo. Ann N Y Acad Sci 719:494–501. doi:10.1111/j.1749-6632.1994.tb56854.x

    PubMed  CAS  Google Scholar 

  • Anisimov VN (1995) Effect of aging and interval between primary and secondary treatment in carcinogenesis induced by neonatal exposure to 5-bromodeoxyuridine and subsequent administration of N-nitrosomethylurea in rats. Mutat Res 316:173–187

    PubMed  CAS  Google Scholar 

  • Anisimov VN (2003a) Insulin/IGF-1 signaling pathway driving aging and cancer as a target for pharmacological intervention. Exp Gerontol 38:1041–1049. doi:10.1016/S0531-5565(03)00169-4

    PubMed  CAS  Google Scholar 

  • Anisimov VN (2003b) Molecular and physiological mechanisms of aging. Nauka, St. Petersburg

    Google Scholar 

  • Anisimov VN (2003c) The relationship between aging and carcinogenesis: a critical appraisal. Crit Rev Oncol Hematol 45:277–304. doi:10.1016/S1040-8428(02)00121-X

    PubMed  Google Scholar 

  • Anisimov VN (2006) Effect of host age on tumor growth rate in rodents. Front Biosci 11:412–422. doi:10.2741/1808

    PubMed  CAS  Google Scholar 

  • Anisimov VN (2008) Antidiabetic drugs in aging and cancer: results and perspectives. Open Aging J 2:36–48

    CAS  Google Scholar 

  • Anisimov VN, Osipova GY (1992) Effect of neonatal exposure to 5-bromo-2′-deoxyuridine on life span, estrus function and tumor development in rats—an argument in favor of the mutation theory of aging? Mutat Res 275:97–110

    PubMed  CAS  Google Scholar 

  • Anisimov VN, Zhukovskaya NV, Loktionov AS, Vakhtin YB (1988) Influence of host age on lung colony forming capacity of injected rat rhabdomyosarcoma cells. Cancer Lett 40:77–82. doi:10.1016/0304-3835(88)90264-9

    PubMed  CAS  Google Scholar 

  • Anisimov VN, Zhukovskaya NV, Loktionov AS, Kamisnkaya E, Vakhtin YB (1995) Host and donor age dependency of colony forming capacity of lung-affine rat rhabdomyosarcoma RA-2 cells. Abstracts of the international conference on tumor microenvironment: progression, therapy and prevention. Tiberias, Israel:6

  • Anisimov SV, Volkova MV, Lenskaya LV et al (2001) Age-associated accumulation of the Apolipoprotein C-III gene T-455C polymorphism C allele in a Russian population. J Gerontol Biol Sci 56A:B27–B32

    CAS  Google Scholar 

  • Anisimov VN, Semenchenko AV, Yashin AI (2003) Insulin and longevity: antidiabetic biguanides as geroprotectors. Biogerontology 4:297–307. doi:10.1023/A:1026299318315

    PubMed  CAS  Google Scholar 

  • Anisimov VN, Berstein LM, Egormin PA, Piskunova TS, Popovich IG, Zabezhinski MA, Kovalenko IG, Poroshina TE, Semenchenko AV, Provinciali M, Re F, Franceschi C (2005a) Effect of metformin on life span and on the development of spontaneous mammary tumors in HER-2/neu transgenic mice. Exp Gerontol 40:685–693. doi:10.1016/j.exger.2005.07.007

    PubMed  CAS  Google Scholar 

  • Anisimov VN, Ukraintseva SV, Yashin AI (2005b) Cancer in rodents: does it tell us about cancer in humans? Nat Rev Cancer 5:807–819. doi:10.1038/nrc1715

    PubMed  CAS  Google Scholar 

  • Anisimov VN, Berstein LM, Egormin PA, Piskunova TS, Popovich IG, Zabezhinski MA, Tyndyk ML, Yurova MV, Kovalenko IG, Poroshina TE, Semenchenko AV (2008) Metformin slows down aging and extends life span of female SHR mice. Cell Cycle 7:2769–2773

    PubMed  CAS  Google Scholar 

  • Arutjunyan AV, Kerkeshko GO, Anisimov VN et al (2001) Disturbances of diurnal rhythms of biogenic amines contents in hypothalamic nuclei as an evidence of neurotropic effects of enterotropic carcinogen 1,2-dimethylhydrazyine. Neuroendocr Lett 22:229–237

    CAS  Google Scholar 

  • Balducci L, Ershler WB (2005) Cancer and ageing: a nexus at several levels. Nat Rev Cancer 5:655–662. doi:10.1038/nrc1675

    PubMed  CAS  Google Scholar 

  • Barbieri M, Rizzo MR, Manzella D et al (2003) Glucose regulation and oxidative stress in healthy centenarians. Exp Gerontol 38:137–143

    PubMed  CAS  Google Scholar 

  • Bartke A, Chandrashekar V, Dominici F, Turyn D, Kinney B, Steger R, Kopchick JJ (2003) Insulin-like growth factor 1 (IGF-1) and aging: controversies and new insights. Biogerontology 4:1–8. doi:10.1023/A:1022448532248

    PubMed  CAS  Google Scholar 

  • Bartsch C, Bartsch H, Blask D, Cardinali DP, Hrushevsky WJM, Mecke D (eds) (2001) The pineal galand and cancer. Springer, Berlin

    Google Scholar 

  • Barzilai N, Gupta G (1999) Interaction between aging and syndrome X: new insights on the pathophysiology of fat distribution. Ann N Y Acad Sci 892:58–72. doi:10.1111/j.1749-6632.1999.tb07785.x

    PubMed  CAS  Google Scholar 

  • Bataller M, Mendez C, Salas JA, Portugal J (2008) Mithramycin SK modulates polyploidy and cell death in colon carcinoma cells. Mol Cancer Ther 7:2988–2997. doi:10.1158/1535-7163.MCT-08-0420

    PubMed  CAS  Google Scholar 

  • Berenblum I (1975) Sequential aspects of chemical carcinogenesis: skin. In: Becker J (ed) Cancer—a comprehensive treatise. Plenum, New York, pp 323–344

    Google Scholar 

  • Berns A (2002) Senescence: a companion in chemotherapy? Cancer Cell 1:309–311. doi:10.1016/S1535-6108(02)00063-6

    PubMed  CAS  Google Scholar 

  • Berstein LM (2005) Clinical usage of hypolipidemic and antidiabetic drugs in the prevention and treatment of cancer. Cancer Lett 224:203–212. doi:10.1016/j.canlet.2004.11.011

    PubMed  CAS  Google Scholar 

  • Berstein LM, Kvatchevskaya JO, Poroshina TE, Kovalenko IG, Tsyrlina EV, Zimarina TS, Ourmantcheeva AF, Ashrafian L, Thijssen JH (2004) Insulin resistance, its consequences for clinical course of the disease and possibilities of correction in endometrial cancer. J Cancer Res Clin Oncol 130:687–693

    PubMed  CAS  Google Scholar 

  • Bluher M, Kahn BB, Kahn CR (2003) Extended longevity in mice lacking the insulin receptor in adipose tissue. Science 299:572–574

    PubMed  Google Scholar 

  • Bordin P, Da Gol PG, Peruzzo P et al (1999) Causes of death and clinical diagnostic error in extreme aged hosptalized people: a retrospective clinical-necropsy survey. J Gerontol Med Sci 54A:M554–M559

    Google Scholar 

  • Bowker SL, Majumdar SR, Veugelers P, Johnson JA (2006) Increased cancer-related mortality for patients with type 2 diabetes who use sulfonylureas or insulin. Diabetes Care 29:254–258. doi:10.2337/diacare.29.02.06.dc05-1558

    PubMed  Google Scholar 

  • Butov AA, Volkov MA, Anisimov VN, Sehl ME, Yashin AI (2002) A model of accelerated aging induced by 5-bromodeoxyuridine. Biogerontology 3:175–182. doi:10.1023/A:1015647225196

    PubMed  CAS  Google Scholar 

  • Campisi J (2000) Cancer, aging, and cellular senescence. In Vivo 14:183–188

    PubMed  CAS  Google Scholar 

  • Campisi J (2003) Cellular senescence and apoptosis: how cellularresponses might influenceaging phenotypes. Exp Gerontol 38:5–11. doi:10.1016/S0531-5565(02)00152-3

    PubMed  CAS  Google Scholar 

  • Campisi J (2005) Senescent cells, tumor suppression, and organismal aging: good citizens, bad neighbors. Cell 120:513–522. doi:10.1016/j.cell.2005.02.003

    PubMed  CAS  Google Scholar 

  • Campisi J, Kim S, Lim CS, Rubio M (2001) Cellular senescence, cancer and aging: the telomere connection. Exp Gerontol 36:1619–1637. doi:10.1016/S0531-5565(01)00160-7

    PubMed  CAS  Google Scholar 

  • Chang BD, Xuan Y, Broude EV, Zhu H, Schott B, Fang J, Roninson IB (1999) Role of p53 and p21waf1/cip1 in senescence-like terminal proliferation arrest induced in human tumor cells by chemotherapeutic drugs. Oncogene 18:4808–4818. doi:10.1038/sj.onc.1203078

    PubMed  CAS  Google Scholar 

  • Chiba T, Yamaza H, Higami Y, Shimokawa I (2002) Anti-aging effects of caloric restriction: involvement of neuroendocrine adaptation by peripheral signaling. Microsc Res Tech 59:317–324. doi:10.1002/jemt.10211

    PubMed  CAS  Google Scholar 

  • Choi J, Shendrik I, Peacocke M (2000) Expression of senescence-associated beta-galactosidase in enlarged prostates from men with benign prostatic hyperplasia. Urology 56:160–166. doi:10.1016/S0090-4295(00)00538-0

    PubMed  CAS  Google Scholar 

  • Colangelo LA, Gapstur SM, Gann PH (2002) Colorectal cancer mortality and factors related to the insulin resistance syndrome. Cancer Epidemiol Biomarkers Prev 11:385–391

    PubMed  Google Scholar 

  • Coschigano KT, Clemmons D, Bellush LL, Kopchick JJ (2000) Assessment of growth parameters and life span of GHR/BP gene-disrupted mice. Endocrinology 141:2608–2613

    PubMed  CAS  Google Scholar 

  • Cristofalo VJ (2005) SA β Gal staining: biomarker or delusion. Exp Gerontol 40:836–838. doi:10.1016/j.exger.2005.08.005

    PubMed  CAS  Google Scholar 

  • DePinho RA (2000) The age of cancer. Nature 408:248–254. doi:10.1038/35041694

    PubMed  CAS  Google Scholar 

  • Derhovanessian E, Solana R, Larbi A, Pawelec G (2008) Immunity, ageing and cancer. Immun Ageing 15:11

    Google Scholar 

  • Dillin A, Crawford DK, Kenyon C (2002) Timing requirements for insulin/IGF-1 signaling in C. elegans. Science 298:830–834. doi:10.1126/science.1074240

    PubMed  CAS  Google Scholar 

  • Dilman VM (1971) Age-associated elevation of hypothalamic threshold to feedback control and its role in development, aging and disease. Lancet 1:1211–1219. doi:10.1016/S0140-6736(71)91721-1

    PubMed  CAS  Google Scholar 

  • Dilman VM (1994) Development, aging, and disease. A new rationale for and intervention strategy. Harwood, Chur

    Google Scholar 

  • Dilman VM, Anisimov VN (1979a) Hypothalamic mechanisms of ageing and of specific age pathology-I. Sensitivity threshold of hypothalamo-pituitary complex to homeostatic stimuli in the reproductive system. Exp Gerontol 14:161–174. doi:10.1016/0531-5565(79)90015-9

    PubMed  CAS  Google Scholar 

  • Dilman VM, Anisimov VN (1979b) Potentiation of antitumor effect of cyclophosphamide and hydrazine sulfate by treatment with the antidiabetic agent, 1-phenylethylbiguanide (phenformin). Cancer Lett 7:357–361. doi:10.1016/S0304-3835(79)80066-X

    PubMed  CAS  Google Scholar 

  • Dilman VM, Anisimov VN (1980) Effect of treatment with phenofromin, dyphenylhydantoin or L-DOPA on life span and tumor incidence in C3H/Sn mice. Gerontology 26:241–245

    Article  PubMed  CAS  Google Scholar 

  • Dimri GP (2005) What has senescence got to do with cancer? Cancer Cell 7:505–512. doi:10.1016/j.ccr.2005.05.025

    PubMed  CAS  Google Scholar 

  • Dimri GP, Lee X, Basile G, Acosta M (1995) A novel biomarker identifies senescent human cells in culture and in aging skin in vivo. Proc Natl Acad Sci USA 92:9363–9367. doi:10.1073/pnas.92.20.9363

    PubMed  CAS  Google Scholar 

  • Dirks AJ, Leeuwenburgh C (2005) Caloric restriction in humans: potential pitfalls and health concerns. Mech Ageing Dev 127:1–7. doi:10.1016/j.mad.2005.09.001

    PubMed  Google Scholar 

  • Dix D, Cohen P (1999) On the role of aging in carcinogenesis. Anticancer Res 19:723–726

    PubMed  CAS  Google Scholar 

  • Dix D, Cohen P, Flannery J (l980) On the role of aging in cancer incidence. J Theor Biol 83:163–173

    PubMed  CAS  Google Scholar 

  • Dominici FP, Arosegui Diaz G, Bartke A (2000) Compensatory alterations of insulin signal transduction in liver of growth hormone receptor knockout mice. J Endocrinol 166:579–590. doi:10.1677/joe.0.1660579

    PubMed  CAS  Google Scholar 

  • Dominici FP, Hauck S, Argention DP (2002) Increased insulin sensitivity and upregulation of insulin receptor, insulin receptor substrate (ISR)-1 and IRS-2 in liver of Ames dwarf mice. J Endocrinol 173:81–94. doi:10.1677/joe.0.1730081

    PubMed  CAS  Google Scholar 

  • El Mir MY, Nogueira V, Fontaine E (2000) Dimethylbiguanide inhibits cell respiration via an indirect effect targeted on the respiratory chain complex I. J Biol Chem 275:223–228. doi:10.1074/jbc.275.1.223

    PubMed  CAS  Google Scholar 

  • Eom YW, Kim MA, Park SS, Goo MJ, Kwon HJ, Sohn S, Kim WH, Yoon G, Choi KS (2005) Two distinct modes of cell death induced by doxorubicin: apoptosis and cell death through mitotic catastrophe accompanied by senescence-like phenotype. Oncogene 24:4765–4777. doi:10.1038/sj.onc.1208627

    PubMed  CAS  Google Scholar 

  • Erenpreisa J, Cragg MS (2007) Cancer: a matter of life cycle? Cell Biol Int 31:1507–1510. doi:10.1016/j.cellbi.2007.08.013

    PubMed  CAS  Google Scholar 

  • Evans JMM, Donnely LA, Emslie-Smith AM (2005) Metformin and reduced risk of cancer in diabetic patients. BMJ 330:1304–1305. doi:10.1136/bmj.38415.708634.F7

    PubMed  Google Scholar 

  • Facchini FS, Hua NW, Reaven GM, Stoohs RA (2000) Hyperinsulinemia: the missing link among oxidative stress and age-related diseases? Free Radic Biol Med 29:1302–1306. doi:10.1016/S0891-5849(00)00438-X

    PubMed  CAS  Google Scholar 

  • Flurkey K, Papaconstantinou J, Miller RA, Harrison DE (2001) Life-span extension and delayed immune and collagen aging in mutant mice with defects in growth hormone production. Proc Natl Acad Sci USA 98:6736–6741

    PubMed  CAS  Google Scholar 

  • Fruehwald-Schultes B, Oltmanns KM, Toschek B (2002) Short-term treatment with metformin decreases serum leptin concentration without affecting body weight and body fat content in normal-weight healthy men. Metabolism 51:531–536. doi:10.1053/meta.2002.31332

    PubMed  CAS  Google Scholar 

  • Gargiulo P, Caccese D, Pignatelli P et al (2002) Metformin decreases platelet superoxide anion production in diabetic patients. Diabetes Metab Res Rev 18:156–159

    PubMed  CAS  Google Scholar 

  • Gravekamp C, Kim SH, Castro F (2008) Cancer vaccination: manipulation of immune responses at old age. Mech Ageing Dev. doi:10.1016/j.mad.2008.05.003

  • Gupta K, Krishnaswamy G, Karnad A, Peiris AN (2002) Insulin: a novel factor in carcinogenesis. Am J Med Sci 323:140–145

    PubMed  CAS  Google Scholar 

  • Hahn WC, Weinberg RA (2002) Modeling the molecular circuitry of cancer. Nat Rev Cancer 2:331–341. doi:10.1038/nrc795

    PubMed  CAS  Google Scholar 

  • Hamilton ML, Van Remmen H, Drake JA (2001) Does oxidative damage to DNA increase with age? Proc Natl Acad Sci USA 98:10469–10474. doi:10.1073/pnas.171202698

    PubMed  CAS  Google Scholar 

  • Han Z, Wei W, Dunaway S, Darnowski JW, Calabresi P, Sedivy J, Hendrickson EA, Balan KV, Pantazis P, Wyche JH (2002) Role of p21 in apoptosis and senescence of human colon cancer cells treated with camptothecin. J Biol Chem 277:17154–17160. doi:10.1074/jbc.M112401200

    PubMed  CAS  Google Scholar 

  • Hanahan D, Weinberg RA (2000) The hallmarks of cancer. Cell 100:57–70

    PubMed  CAS  Google Scholar 

  • Harman D (1998) Extending functional life span. Exp Gerontol 33:95–112. doi:10.1159/000028983

    PubMed  CAS  Google Scholar 

  • Herbig U, Ferreira M, Condel L, Carey D, Sedivy JM (2006) Cellular senescence in aging primates. Science 311:1257. doi:10.1126/science.1122446

    PubMed  CAS  Google Scholar 

  • Holzenberger M, Dupond J, Ducos B (2003) IGF-1 receptor regulates lifespan and resistance to oxidative stress in mice. Nature 421:182–187. doi:10.1038/nature01298

    PubMed  CAS  Google Scholar 

  • Hsieh CC, DeFord JH, Flurkey K (2002a) Effects of the Pit1 mutation on the insulin signaling pathway: implications on the longevity of the long-lived Snell dwarf mouse. Mech Ageing Dev 123:1245–1255. doi:10.1016/S0047-6374(02)00037-4

    PubMed  CAS  Google Scholar 

  • Hsieh CC, DeFord JH, Flurkey K et al (2002b) Implications for the insulin signaling pathway in Snell dwarf mouse longevity: a similarity with the C. elegans longevity paradigm. Mech Ageing Dev 123:1229–1244

    PubMed  CAS  Google Scholar 

  • Hu M, Polyak K (2008) Microenvironmental regulation of cancer development. Curr Opin Genet Dev 18:27–34. doi:10.1016/j.gde.2007.12.006

    PubMed  CAS  Google Scholar 

  • Ikeno Y, Bronson RT, Hubbard GB (2003) Delayed occurrence of fatal neoplastic diseases in Ames dwarf mice: correlation to extended longevity. J Gerontol A Biol Sci Med Sci 58:B291–B296

    Google Scholar 

  • Itahana K, Campisi J, Dimri GP (2004) Mechanisms of cellular senescence in huma and mouse cells. Biogerontology 5:1–10. doi:10.1023/B:BGEN.0000017682.96395.10

    PubMed  CAS  Google Scholar 

  • Jackson JG, Pereira-Smith OM (2006) Primary and compensatory roles for RB family members at cell cycle gene promoters that are deacetylated and downregulated in doxorubicin-induced senescence of breast cancer cells. Mol Cell Biol 26:2501–2510. doi:10.1128/MCB.26.7.2501-2510.2006

    PubMed  CAS  Google Scholar 

  • Kawanishi S, Hiraki Y, Oikawa S (2001) Mechanism of guanine-specific DNA damage by oxidative stress and its role in carcinogenesis and aging. Mutat Res 488:65–67. doi:10.1016/S1383-5742(00)00059-4

    PubMed  CAS  Google Scholar 

  • Kenyon C (2001) A conserved regulatory system for aging. Cell 105:165–168

    PubMed  CAS  Google Scholar 

  • Kim JH, Kim JH, Lee GE, Kim SW, Chung IK (2003) Identification of a quinoxaline derivative that is a potent telomerase inhibitor leading to cellular senescence of human cancer cells. Biochem J 373:523–529. doi:10.1042/BJ20030363

    PubMed  CAS  Google Scholar 

  • Krtolica A, Parinello S, Locckett S, Campisi J (2001) Senescent fibroblasts promote epithelial cell growth and tumorigenesis: a link between cancer and aging. Proc Natl Acad Sci USA 98:12072–12077. doi:10.1073/pnas.211053698

    PubMed  CAS  Google Scholar 

  • Lane MA, Tilmont EM, De Angelis H (2000) Short-term calorie restriction improves disease-related markers in older male rhesus monkeys (Macaca mulatta). Mech Ageing Dev 112:185–196. doi:10.1016/S0047-6374(99)00087-1

    PubMed  CAS  Google Scholar 

  • Lee J, Chan SL, Lane MA, Mattson MP (2002) Phenformin suppresses calcium responses to glutamate and protects hippocampal neurons against excitotoxicity. Exp Neurol 175:161–167. doi:10.1006/exnr.2002.7864

    PubMed  CAS  Google Scholar 

  • Lipman RD, Dallal GE, Bronson RT (1999a) Lesion biomarkers of aging in B6C3F1 hybrid mice. J Gerontol Med Sci 54A:466–477

    Google Scholar 

  • Lipman RD, Dallal GE, Bronson RT (1999b) Effect of genotype and diet on age-related lesions in ad libitum fed and calorie-restricted F344, BN, and BNF3F1 rats. J Gerontol Med Sci 54A:478–491

    Google Scholar 

  • Mattson MP, Duan W, Lee J et al (2001) Progress in the development of caloric restriction mimetic dietary supplements. J Anti-Aging Med 4:225–232

    Google Scholar 

  • McCullough KD, Coleman WB, Smith GJ, Grisham JW (1994) Age-dependent regulation of the tumorigenic potential of neoplastically transformed rat liver epithelial cells by the liver micro- environment. Cancer Res 54:3668–3671

    PubMed  CAS  Google Scholar 

  • Michishita E, Nakabayashi K, Suzuki T (1999) 5-bromodeoxyuridine induces senescence-like phenomena in mammalian cells regardless of cell type or species. J Biochem 125:1052–1059

    Google Scholar 

  • Mick GJ, Wang X, Ling FC, McCormick KL (2000) Inhibition of leptin secretion by insulin and metformin in cultured rat adipose tissue. Biochim Biophys Acta 1502:426–432

    PubMed  CAS  Google Scholar 

  • Mikhnin AE, Barchuk AS, Wagner RI (2004) Kinetics of visual growth of skin melanoma. Russ Oncol J 2:29–32

    Google Scholar 

  • Miller RA (1991) Gerontology as oncology. Cancer 68:2496–2501. doi:10.1002/1097-0142(19911201)68:11+<2496∷AID-CNCR2820681503>3.0.CO;2-B

    PubMed  CAS  Google Scholar 

  • Minagawa S, Nakabayashi K, Fujii M et al (2004) Functional and chromosomal clustering of genes responsive to 5-bromodeoxyuridine in human cells. Exp Gerontol 39:1069–1078

    PubMed  CAS  Google Scholar 

  • Minagawa S, Nakabayashi K, Fujii M (2005) Early BrdU-resposive genes constitute a novel class of senescence-asscoiated genes in human cells. Exp Cell Res 304:552–558. doi:10.1016/j.yexcr.2004.10.036

    PubMed  CAS  Google Scholar 

  • Mishima K, Handa JT, Aotaki-Keen A (1999) Senescence-associated beta-galactosidase histochemistry for the primate eye. Investig Ophralmol Vis Sci 40:1590–1593

    CAS  Google Scholar 

  • Moolgavkar S, Krewski D, Zeise L (eds) (1999) Quantitative estimation and prediction of human cancer risk. IARC Sci Publ No 131. IARC, Lyon

    Google Scholar 

  • Morris SH (1991) The genetic toxicology of 5-bromodeoxyuridine in mammalian cells. Mutat Res 258:161–188

    PubMed  CAS  Google Scholar 

  • Muntoni S (1999) Metformin and fatty acids. Diabetes Care 22:179–180

    PubMed  CAS  Google Scholar 

  • Napalkov NP (2004) Cancer and demographic transition. Vopr Onkol 50:127–144

    PubMed  CAS  Google Scholar 

  • Napalkov NP, Anisimov VN, Likhachev AJ, Tomatis L (1989) 5-bromodeoxyuridine- induced carcinogenesis and its modification by persistent estrus syndrome, unilateral nephrectomy, and X-irradiation in rats. Cancer Res 49:318–323

    PubMed  CAS  Google Scholar 

  • Narita M, Lowe SW (2005) Senescence comes of age. Nat Med 11:920–922. doi:10.1038/nm0905-920

    PubMed  CAS  Google Scholar 

  • Niculescu AB, Chen X, Smeets M, Hengst L, Prives C, Reed SI (1998) Effects of p21(Cip1/Waf1) at both the G1/S and the G2/M cell cycle transitions: pRb is a critical determinant in blocking DNA replication and in preventing endoreduplication. Mol Cell Biol 18:629–643

    PubMed  CAS  Google Scholar 

  • Ota H, Tokunaga E, Chang K, Hikasa M, Iijima K, Eto M, Kozaki K, Akishita M, Ouchi Y, Kaneki M (2006) Sirt1 inhibitor, Sirtinol, induces senescence-like growth arrest with attenuated Ras-MAPK signaling in human cancer cells. Oncogene 25:176–185

    PubMed  CAS  Google Scholar 

  • Paolisso G, Amato L, Eccellente R et al (1998) Effect of metformin on food intake in obese subjects. Eur J Clin Invest 28:441–446. doi:10.1046/j.1365-2362.1998.00304.x

    PubMed  CAS  Google Scholar 

  • Paradis V, Youssef N, Dargere D (2001) Replicative senescence in normal liver, chronic hepatitis C, and hepatocellular carcinomas. Hum Pathol 32:327–332. doi:10.1053/hupa.2001.22747

    PubMed  CAS  Google Scholar 

  • Parkin DM, Bray FI, Devesa SS (2001) Cancer burden in the year 2000. The global picture. Eur J Cancer 37(Suppl 8):S4–S66. doi:10.1016/S0959-8049(01)00267-2

    PubMed  Google Scholar 

  • Pawelec G, Solana R (2008) Are cancer and ageing different sides of the same coin? Conference on cancer and ageing. EMBO Rep 9:234–238. doi:10.1038/embor.2008.12

    PubMed  CAS  Google Scholar 

  • Pawelec G, Koch S, Griessemann H, Rehbein A, Hähnel K, Gouttefangeas C (2006) Immunosenescence, suppression and tumour progression. Cancer Immunol Immunother 55:981–986. doi:10.1007/s00262-005-0109-3

    PubMed  CAS  Google Scholar 

  • Peto R, Parish SE, Gray RG (1985) There is no such thing as ageing, and cancer is not related to it, 58. In: Likhachev A, Anisimov V, Montesano R (eds) Age-related factors in carcinogenesis. IARC, Lyon, pp 43–53

    Google Scholar 

  • Ponten J (1977) Abnormal cell growth (neoplasia} and aging. In: Finch CE, Hayflick L (eds) Handbook of the biology of aging. van Nostrand Reinhold Co, New York, pp 536–560

    Google Scholar 

  • Puig PE, Guilly MN, Bouchot A, Droin N, Cathelin D, Bouyer F, Favier L, Ghiringhelli F, Kroemer G, Solary E, Martin F, Chauffert B (2008) Tumor cells can escape DNA-damaging cisplatin through DNA endoreduplication and reversible polyploidy. Cell Biol Int 32(9):1031–1043

    PubMed  CAS  Google Scholar 

  • Rangarajan A, Weinberg RA (2003) Comparative biology of mouse versus human cells: modelling human cancer in mice. Nat Rev Cancer 3:952–959. doi:10.1038/nrc1235

    PubMed  CAS  Google Scholar 

  • Rebbaa A, Zheng X, Chu F, Mirkin BL (2006) The role of histone acetylation versus DNA damage in drug-induced senescence and apoptosis. Cell Death Differ 13:1960–1967. doi:10.1038/sj.cdd.4401895

    PubMed  CAS  Google Scholar 

  • Ressler S, Bartkova J, Niederegger H, Bartek J, Scharffetter-Kochanek K, Jansen-Dürr P, Wlaschek M (2006) p16INK4A is a robust in vivo biomarker of cellular aging in human skin. Aging Cell 5:379–389. doi:10.1111/j.1474-9726.2006.00231.x

    PubMed  CAS  Google Scholar 

  • Reya T, Morrison SJ, Clarke MF, Weissman IL (2001) Stem cells, cancer, and cancer stem cells. Nature 414:105–111. doi:10.1038/35102167

    PubMed  CAS  Google Scholar 

  • Richards JS, Russell DL, Ochsner S (2002) Novel signaling pathways that control ovarian follicular development, ovulation, and luteinization. Recent Prog Horm Res 57:195–220. doi:10.1210/rp.57.1.195

    PubMed  CAS  Google Scholar 

  • Roberson RS, Kussick SJ, Vallieres E, Chen SY, Wu DY (2005) Escape from therapy-induced accelerated cellular senescence in p53-null lung cancer cells and in human lung cancers. Cancer Res 65:2795–2803. doi:10.1158/0008-5472.CAN-04-1270

    PubMed  CAS  Google Scholar 

  • Roninson IB (2003) Tumor cell senescence in cancer treatment. Cancer Res 63:2705–2715

    PubMed  CAS  Google Scholar 

  • Roth GS, Lane MA, Ingram D et al (2002) Biomarkers of caloric restriction may predict longevity in humans. Science 297:811

    PubMed  CAS  Google Scholar 

  • Ruiz-Torres A, Soares de Melo Kirzner M (2002) Ageing and longevity are related to growth hormone/insulin-like growth factor-1 secretion. Gerontology 48:401–407

    PubMed  CAS  Google Scholar 

  • Schmitt CA, Fridman JS, Yang M (2002) A senescent program controlled by p53 and p16INK4a contributes to the outcome of cancer therapy. Cell 109:335–346. doi:10.1016/S0092-8674(02)00734-1

    PubMed  CAS  Google Scholar 

  • Schneider MB, Matsuzaki H, Harorah J (2001) Prevention of pancreatic cancer induction in hamsters by metformin. Gastroenterology 120:1263–1270. doi:10.1053/gast.2001.23258

    PubMed  CAS  Google Scholar 

  • Shay JW, Roninson IB (2004) Hallmarks of senescence in carcinogenesis and cancer therapy. Oncogene 23:2919–2933. doi:10.1038/sj.onc.1207518

    PubMed  CAS  Google Scholar 

  • Shimokawa I, Higami Y, Utsuyama M et al (2002) Life span extension by reducing in growth hormone-insulin-growth factor-1 axis in a transgenic rat model. Am J Pathol 160:2259–2265

    PubMed  CAS  Google Scholar 

  • Simpson AJG (1993) A natural somatic mutation frequency and human carcinogenesis. Adv Cancer Res 71:209–240. doi:10.1016/S0065-230X(08)60100-1

    Google Scholar 

  • Singer B, Grunberger D (1983) Molecular Biology of Mutagens and Carcinogens. Plenum, New York

    Google Scholar 

  • Sliwinska MA, Mosieniak G, Wolanin K, Babik A, Piwocka K, Magalska A, Szczepanowska J, Fronk J, Sikora E (2008) Induction of senescence with doxorubicin leads to increased genomic instability of HCT116 cells. Mech Ageing Dev (in press)

  • Spindler SR (2006) Use of microarray biomarkers to identify longevity therapeutics. Aging Cell 5:39–50. doi:10.1111/j.1474-9726.2006.00194.x

    PubMed  CAS  Google Scholar 

  • Srinivasan SV, Mayhew CN, Schwemberger S, Zagorski W, Knudsen ES (2007) RB loss promotes aberrant ploidy by deregulating levels and activity of DNA replication factors. J Biol Chem 282:23867–23877. doi:10.1074/jbc.M700542200

    PubMed  CAS  Google Scholar 

  • Staats J (1980) Standardized nomenclature for inbred strains of mice: seventh listing. Cancer Res 40:2083–2128

    PubMed  CAS  Google Scholar 

  • Storchova Z, Pellman D (2004) From polyploidy to aneuploidy, genome instability and cancer. Nat Rev Mol Cell Biol 5:45–54. doi:10.1038/nrm1276

    PubMed  CAS  Google Scholar 

  • Sundaram M, Guernsey DL, Rajaraman MM, Rajaraman R (2004) Neosis: a novel type of cell division in cancer. Cancer Biol Ther 3:207–218

    PubMed  CAS  Google Scholar 

  • Suzuki T, Minagawa S, Michishita E et al (2001) Induction of senescence-associated genes by 5-bromodeoxyuridine in HeLa cells. Exp Gerontol 36:465–474. doi:10.1016/S0531-5565(00)00223-0

    PubMed  CAS  Google Scholar 

  • Tatar M, Bartke A, Antebi A (2003) The endocrine regulation of aging by insulin-like signals. Science 299:1346–1351

    PubMed  CAS  Google Scholar 

  • te Poele RH, Okorokov AL, Jardine L, Cummings J, Joel SP (2002) DNA damage is able to induce senescence in tumor cells in vitro and in vivo. Cancer Res 62:1876–1883

    PubMed  CAS  Google Scholar 

  • Tomatis L (ed) (1990) Cancer: causes, occurence and control. IARC Sci Publ No100. IARC, Lyon

    Google Scholar 

  • Touitou Y (2001) Human aging and melatonin. Clinical relevance. Exp Gerontol 36:1083–1100

    PubMed  CAS  Google Scholar 

  • Toyokuni SM (2008) Molecular mechanisms of oxidative stress-induced carcinogfenesis: from epidemiology to oxygenomics. IUBMB Life 60:441–447. doi:10.1002/iub.61

    PubMed  CAS  Google Scholar 

  • Ulrich P, Cerami A (2001) Protein glycation, diabetes, and aging. Recent Progr Horm Res 56:1–21

    PubMed  CAS  Google Scholar 

  • Vasile E, Tomita Y, Brown LF (2001) Differential expression of thymosin beta-1- by early passage and senescent vascular endothelium is modulated by VPF/VEGF: evidence for senescent endothelial cells in vivo at sited of atherosclerosis. FASEB J 15:6449–6465. doi:10.1096/fj.00-0051com

    Google Scholar 

  • Vijg J, Campisi J (2008) Puzzles, promises and a cure for ageing. Nature 454:1065–1071

    PubMed  CAS  Google Scholar 

  • Vogel C, Kienitz A, Hofmann I, Muller R, Bastians H (2004) Crosstalk of the mitotic spindle assembly checkpoint with p53 to prevent polyploidy. Oncogene 23:6845–6853. doi:10.1038/sj.onc.1207860

    PubMed  CAS  Google Scholar 

  • von Wangenheim KH, Peterson HP (1998) Control of cell proliferation by progress in differentiation: clues to mechanisms of aging, cancer causation and therapy. J Theor Biol 193:663–678. doi:10.1006/jtbi.1998.0731

    Google Scholar 

  • von Zglinicki T, Burkle A, Kirkwood TBL (2001) DNA damage and ageing—an integrative approach. Exp Gerontol 36:1049–1062. doi:10.1016/S0531-5565(01)00111-5

    Google Scholar 

  • Walter S, Boley G, Bühring H-J, Koch S, Wernet D, Zippelius A, Pawelec G, Romero P, Stevanović S, Rammensee H-G, Gouttefangeas C (2005) High frequencies of functionally impaired cytokeratin 18-specific CD8+ T cells in healthy HLA-A2+ donors. Eur J Immunol 35:2876–2885. doi:10.1002/eji.200526207

    PubMed  CAS  Google Scholar 

  • Ward JM (1983) Background data and variations in tumor rates of control rats and mice. Prog Exp Tumor Res 26:241–264

    PubMed  CAS  Google Scholar 

  • Ward JM, Henneman JR, Osipova GY, Anisimov VN (1991) Persistence of 5-bromo-2′-deoxyuridine in tissues of rats after exposure in early life. Toxicology 70:345–352. doi:10.1016/0300-483X(91)90008-O

    PubMed  CAS  Google Scholar 

  • Weinberg RA (2008) Mechanisms of malignant progression. Carcinogenesis 29:1092–1095. doi:10.1093/carcin/bgn104

    PubMed  CAS  Google Scholar 

  • Weindruch R, Sohal RS (1997) Caloric intake and aging. N Engl J Med 337:986–994. doi:10.1056/NEJM199710023371407

    PubMed  CAS  Google Scholar 

  • Wu Y, Yakar S, Zhao L, Hennighausen L et al (2002) Circulating insulin-like growth factor-I levels regulate colon cancer growth and metastasis. Cancer Res 62:1030–1035

    PubMed  CAS  Google Scholar 

  • Xu WS, Perez G, Ngo L, Gui CY, Marks PA (2005) Induction of polyploidy by histone deacetylase inhibitor: a pathway for antitumor effects. Cancer Res 65:7832–7839. doi:10.1158/0008-5472.CAN-04-4313

    PubMed  CAS  Google Scholar 

  • Zhou G, Myers R, Li Y (2001) Role of AMP-activated protein kinase in mechanism of metformin action. J Clin Invest 108:1167–1174

    PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This paper evolved from discussions initiated at the The European Conference on Cancer and Aging—SeneCa, senescence and cancer—which took place in Warsaw, Poland between 4th and 6th October 2007, supported by the European Commission (contract LSSM-CT-2006-037312). For a summary of the main presentations at the conference, see Pawelec and Solana (2008). VA is supported by grant NS-5054.2006.4 from the President of The Russian Federation. ES was supported by the Ministry of Science and Higher Education (grant N301 008 32/0549).

Author information

Authors and Affiliations

  1. Department of Carcinogenesis and Oncogerontology, N. N. Petrov Research Institute of Oncology, Pesochny-2, St. Petersburg, 197758, Russia

    Vladimir N. Anisimov

  2. NENCKI Institute of Experimental Biology, Warsaw, Poland

    Ewa Sikora

  3. Center for Medical Research, University of Tübingen Medical School, Tübingen, Germany

    Graham Pawelec

Authors
  1. Vladimir N. Anisimov
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ewa Sikora
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Graham Pawelec
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Vladimir N. Anisimov.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Anisimov, V.N., Sikora, E. & Pawelec, G. Relationships between cancer and aging: a multilevel approach. Biogerontology 10, 323–338 (2009). https://doi.org/10.1007/s10522-008-9209-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10522-008-9209-8

Keywords

Search

Navigation