Skip to main content

Thank you for visiting 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.

The common biology of cancer and ageing


At first glance, cancer and ageing would seem to be unlikely bedfellows. Yet the origins for this improbable union can actually be traced back to a sequence of tragic—and some say unethical—events that unfolded more than half a century ago. Here we review the series of key observations that has led to a complex but growing convergence between our understanding of the biology of ageing and the mechanisms that underlie cancer.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.

Figure 1: The potential interplay between stem cells, stress, ageing and cancer.
Figure 2: Revisiting the telomere hypothesis: role of telomeres in cancer and ageing.
Figure 3: The potential role of autophagy in cancer and ageing.
Figure 4: Energy signal transduction.
Figure 5: A stem cell perspective on cancer and ageing.


  1. 1

    Hayflick, L. & Moorhead, P. S. The serial cultivation of human diploid cell strains. Exp. Cell Res. 25, 585–621 (1961)

    CAS  Google Scholar 

  2. 2

    Serrano, M., Hannon, G. J. & Beach, D. A new regulatory motif in cell-cycle control causing specific inhibition of cyclin D/CDK4. Nature 366, 704–707 (1993)

    ADS  CAS  PubMed  Google Scholar 

  3. 3

    Alcorta, D. A. et al. Involvement of the cyclin-dependent kinase inhibitor p16 (INK4a) in replicative senescence of normal human fibroblasts. Proc. Natl Acad. Sci. USA 93, 13742–13747 (1996)

    ADS  CAS  PubMed  Google Scholar 

  4. 4

    Hara, E. et al. Regulation of p16CDKN2 expression and its implications for cell immortalization and senescence. Mol. Cell. Biol. 16, 859–867 (1996)

    CAS  PubMed  PubMed Central  Google Scholar 

  5. 5

    Mooi, W. J. & Peeper, D. S. Oncogene-induced cell senescence—halting on the road to cancer. N. Engl. J. Med. 355, 1037–1046 (2006)

    CAS  PubMed  Google Scholar 

  6. 6

    Collado, M. & Serrano, M. The power and the promise of oncogene-induced senescence markers. Nature Rev. Cancer 6, 472–476 (2006)

    CAS  Google Scholar 

  7. 7

    Bracken, A. P. et al. The Polycomb group proteins bind throughout the INK4AARF locus and are disassociated in senescent cells. Genes Dev. 21, 525–530 (2007)

    CAS  Article  Google Scholar 

  8. 8

    Bartkova, J. et al. Oncogene-induced senescence is part of the tumorigenesis barrier imposed by DNA damage checkpoints. Nature 444, 633–637 (2006)

    ADS  CAS  PubMed  PubMed Central  Google Scholar 

  9. 9

    Di Micco, R. et al. Oncogene-induced senescence is a DNA damage response triggered by DNA hyper-replication. Nature 444, 638–642 (2006)

    ADS  CAS  PubMed  Google Scholar 

  10. 10

    Xue, W. et al. Senescence and tumour clearance is triggered by p53 restoration in murine liver carcinomas. Nature 445, 656–660 (2007)

    CAS  PubMed  PubMed Central  Google Scholar 

  11. 11

    Ventura, A. et al. Restoration of p53 function leads to tumour regression in vivo. Nature 445, 661–665 (2007)

    CAS  PubMed  PubMed Central  Google Scholar 

  12. 12

    Roninson, I. B. Tumor cell senescence in cancer treatment. Cancer Res. 63, 2705–2715 (2003)

    CAS  PubMed  Google Scholar 

  13. 13

    Gasser, S., Orsulic, S., Brown, E. J. & Raulet, D. H. The DNA damage pathway regulates innate immune system ligands of the NKG2D receptor. Nature 436, 1186–1190 (2005)

    ADS  CAS  PubMed  PubMed Central  Google Scholar 

  14. 14

    Dimri, G. P. et al. A biomarker that identifies senescent human cells in culture and in aging skin in vivo. Proc. Natl Acad. Sci. USA 92, 9363–9367 (1995)

    ADS  CAS  Google Scholar 

  15. 15

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

    CAS  Google Scholar 

  16. 16

    Krishnamurthy, J. et al. Ink4a/Arf expression is a biomarker of aging. J. Clin. Invest. 114, 1299–1307 (2004)

    CAS  PubMed  PubMed Central  Google Scholar 

  17. 17

    Kim, W. Y. & Sharpless, N. E. The regulation of INK4/ARF in cancer and aging. Cell 127, 265–275 (2006)

    CAS  Google Scholar 

  18. 18

    Edwards, M. G. et al. Gene expression profiling of aging reveals activation of a p53-mediated transcriptional program. BMC Genomics 8, 80 (2007)

    PubMed  PubMed Central  Google Scholar 

  19. 19

    Melzer, D. et al. A common variant of the p16(INK4a) genetic region is associated with physical function in older people. Mech. Ageing Dev. published online 27 March 2007 (doi: 10.1016/j.mad.2007.03.005).

    CAS  PubMed  PubMed Central  Google Scholar 

  20. 20

    McPherson, R. et al. A common allele on chromosome 9 associated with coronary heart disease. Science 316, 1488–1491 (2007)

    ADS  CAS  PubMed  PubMed Central  Google Scholar 

  21. 21

    Helgadottir, A. et al. A common variant on chromosome 9p21 affects the risk of myocardial infarction. Science 316, 1491–1493 (2007)

    ADS  CAS  PubMed  Google Scholar 

  22. 22

    Valk-Lingbeek, M. E., Bruggeman, S. W. & van Lohuizen, M. Stem cells and cancer: the polycomb connection. Cell 118, 409–418 (2004)

    CAS  Google Scholar 

  23. 23

    Janzen, V. et al. Stem-cell ageing modified by the cyclin-dependent kinase inhibitor p16INK4a. Nature 443, 421–426 (2006)

    ADS  CAS  Google Scholar 

  24. 24

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

    ADS  CAS  Google Scholar 

  25. 25

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

    ADS  CAS  PubMed  PubMed Central  Google Scholar 

  26. 26

    McMurray, M. A. & Gottschling, D. E. An age-induced switch to a hyperrecombinational state. Science 301, 1908–1911 (2003)

    ADS  CAS  PubMed  Google Scholar 

  27. 27

    Curtis, H. J. Biological mechanisms underlying the aging process. Science 141, 686–694 (1963)

    ADS  CAS  PubMed  Google Scholar 

  28. 28

    Bahar, R. et al. Increased cell-to-cell variation in gene expression in ageing mouse heart. Nature 441, 1011–1014 (2006)

    ADS  CAS  PubMed  Google Scholar 

  29. 29

    Tyner, S. D. et al. p53 mutant mice that display early ageing-associated phenotypes. Nature 415, 45–53 (2002)

    ADS  CAS  PubMed  Google Scholar 

  30. 30

    Maier, B. et al. Modulation of mammalian life span by the short isoform of p53. Genes Dev. 18, 306–319 (2004)

    CAS  PubMed  PubMed Central  Google Scholar 

  31. 31

    Garcia-Cao, I. et al. “Super p53” mice exhibit enhanced DNA damage response, are tumor resistant and age normally. EMBO J. 21, 6225–6235 (2002)

    CAS  PubMed  PubMed Central  Google Scholar 

  32. 32

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

    ADS  CAS  PubMed  Google Scholar 

  33. 33

    Pinkston, J. M., Garigan, D., Hansen, M. & Kenyon, C. Mutations that increase the life span of C. elegans inhibit tumor growth. Science 313, 971–975 (2006)

    ADS  CAS  PubMed  Google Scholar 

  34. 34

    Ito, K. et al. Regulation of oxidative stress by ATM is required for self-renewal of haematopoietic stem cells. Nature 431, 997–1002 (2004)

    ADS  CAS  PubMed  Google Scholar 

  35. 35

    Cao, L., Li, W., Kim, S., Brodie, S. G. & Deng, C. X. Senescence, aging, and malignant transformation mediated by p53 in mice lacking the Brca1 full-length isoform. Genes Dev. 17, 201–213 (2003)

    CAS  PubMed  PubMed Central  Google Scholar 

  36. 36

    Baker, D. J. et al. BubR1 insufficiency causes early onset of aging-associated phenotypes and infertility in mice. Nature Genet. 36, 744–749 (2004)

    CAS  PubMed  Google Scholar 

  37. 37

    Baker, D. J. et al. Early aging-associated phenotypes in Bub3/Rae1 haploinsufficient mice. J. Cell Biol. 172, 529–540 (2006)

    CAS  PubMed  PubMed Central  Google Scholar 

  38. 38

    de Boer, J. et al. Premature aging in mice deficient in DNA repair and transcription. Science 296, 1276–1279 (2002)

    ADS  CAS  PubMed  Google Scholar 

  39. 39

    Niedernhofer, L. J. et al. A new progeroid syndrome reveals that genotoxic stress suppresses the somatotroph axis. Nature 444, 1038–1043 (2006)

    ADS  CAS  Google Scholar 

  40. 40

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

    CAS  Google Scholar 

  41. 41

    Opresko, P. L. et al. The Werner syndrome helicase and exonuclease cooperate to resolve telomeric D loops in a manner regulated by TRF1 and TRF2. Mol. Cell 14, 763–774 (2004)

    CAS  PubMed  Google Scholar 

  42. 42

    Agrelo, R. et al. Epigenetic inactivation of the premature aging Werner syndrome gene in human cancer. Proc. Natl Acad. Sci. USA 103, 8822–8827 (2006)

    ADS  CAS  PubMed  Google Scholar 

  43. 43

    Liu, B. et al. Genomic instability in laminopathy-based premature aging. Nature Med. 11, 780–785 (2005)

    CAS  PubMed  Google Scholar 

  44. 44

    Haigis, M. C. & Guarente, L. P. Mammalian sirtuins—emerging roles in physiology, aging, and calorie restriction. Genes Dev. 20, 2913–2921 (2006)

    CAS  PubMed  Google Scholar 

  45. 45

    Vaquero, A. et al. Human SirT1 interacts with histone H1 and promotes formation of facultative heterochromatin. Mol. Cell 16, 93–105 (2004)

    CAS  PubMed  Google Scholar 

  46. 46

    Pruitt, K. et al. Inhibition of SIRT1 reactivates silenced cancer genes without loss of promoter DNA hypermethylation. PLoS Genet. 2, e40 (2006)

    PubMed  PubMed Central  Google Scholar 

  47. 47

    Mostoslavsky, R. et al. Genomic instability and aging-like phenotype in the absence of mammalian SIRT6. Cell 124, 315–329 (2006)

    CAS  PubMed  Google Scholar 

  48. 48

    Blackburn, E. H. & Gall, J. G. A tandemly repeated sequence at the termini of the extrachromosomal ribosomal RNA genes in Tetrahymena. J. Mol. Biol. 120, 33–53 (1978)

    CAS  PubMed  Google Scholar 

  49. 49

    Shampay, J., Szostak, J. W. & Blackburn, E. H. DNA sequences of telomeres maintained in yeast. Nature 310, 154–157 (1984)

    ADS  CAS  Google Scholar 

  50. 50

    Greider, C. W. & Blackburn, E. H. Identification of a specific telomere terminal transferase activity in Tetrahymena extracts. Cell 43, 405–413 (1985)

    CAS  PubMed  Google Scholar 

  51. 51

    Lundblad, V. & Blackburn, E. H. An alternative pathway for yeast telomere maintenance rescues est1- senescence. Cell 73, 347–360 (1993)

    CAS  PubMed  PubMed Central  Google Scholar 

  52. 52

    Dunham, M. A., Neumann, A. A., Fasching, C. L. & Reddel, R. R. Telomere maintenance by recombination in human cells. Nature Genet. 26, 447–450 (2000)

    CAS  PubMed  Google Scholar 

  53. 53

    Harley, C. B., Futcher, A. B. & Greider, C. W. Telomeres shorten during ageing of human fibroblasts. Nature 345, 458–460 (1990)

    ADS  CAS  Google Scholar 

  54. 54

    Allsopp, R. C. et al. Telomere length predicts replicative capacity of human fibroblasts. Proc. Natl Acad. Sci. USA 89, 10114–10118 (1992)

    ADS  CAS  PubMed  Google Scholar 

  55. 55

    Cawthon, R. M. et al. Association between telomere length in blood and mortality in people aged 60 years or older. Lancet 361, 393–395 (2003)

    CAS  PubMed  Google Scholar 

  56. 56

    Bodnar, A. G. et al. Extension of life-span by introduction of telomerase into normal human cells. Science 279, 349–352 (1998)

    ADS  CAS  Google Scholar 

  57. 57

    Blasco, M. A. et al. Telomere shortening and tumor formation by mouse cells lacking telomerase RNA. Cell 91, 25–34 (1997)

    CAS  PubMed  Google Scholar 

  58. 58

    Lee, H.-W., Blasco, M. A., Gottlieb, G. J., Greider, C. W. & DePinho, R. A. Essential role of mouse telomerase in highly proliferative organs. Nature 392, 569–574 (1998)

    ADS  CAS  PubMed  Google Scholar 

  59. 59

    Herrera, E. et al. Disease states associated to telomerase deficiency appear earlier in mice with short telomeres. EMBO J. 18, 2950–2960 (1999)

    CAS  PubMed  PubMed Central  Google Scholar 

  60. 60

    Flores, I., Cayuela, M. L. & Blasco, M. A. Effects of telomerase and telomere length on epidermal stem cell behavior. Science 309, 1253–1256 (2005)

    ADS  CAS  PubMed  Google Scholar 

  61. 61

    Yamaguchi, H. et al. Mutations in TERT, the gene for telomerase reverse transcriptase, in aplastic anemia. N. Engl. J. Med. 352, 1413–1424 (2005)

    CAS  PubMed  Google Scholar 

  62. 62

    Armanios, M. Y. et al. Telomerase mutations in families with idiopathic pulmonary fibrosis. N. Engl. J. Med. 356, 1317–1326 (2007)

    CAS  PubMed  PubMed Central  Google Scholar 

  63. 63

    Tsakiri, K. D. et al. Adult-onset pulmonary fibrosis caused by mutations in telomerase. Proc. Natl Acad. Sci. USA 104, 7552–7557 (2007)

    ADS  CAS  PubMed  PubMed Central  Google Scholar 

  64. 64

    Mason, P. J., Wilson, D. B. & Bessler, M. Dyskeratosis congenita–a disease of dysfunctional telomere maintenance. Curr. Mol. Med. 5, 159–170 (2005)

    CAS  Google Scholar 

  65. 65

    García-Cao, I. et al. Increased p53 activity does not accelerate telomere-driven aging. EMBO Rep. 7, 546–552 (2006)

    PubMed  PubMed Central  Google Scholar 

  66. 66

    Gonzalez-Suarez, E. et al. Increased epidermal tumors and increased skin wound healing in transgenic mice overexpressing the catalytic subunit of telomerase, mTERT, in basal keratinocytes. EMBO J. 20, 2619–2630 (2001)

    CAS  PubMed  PubMed Central  Google Scholar 

  67. 67

    Artandi, S. E. et al. Constitutive telomerase expression promotes mammary carcinomas in aging mice. Proc. Natl Acad. Sci. USA 99, 8191–8196 (2002)

    ADS  CAS  Google Scholar 

  68. 68

    Gonzalez-Suarez, E., Geserick, C., Flores, J. M. & Blasco, M. A. Antagonistic effects of telomerase on cancer and aging in K5-mTert transgenic mice. Oncogene 24, 2256–2270 (2005)

    CAS  PubMed  Google Scholar 

  69. 69

    Sarin, K. Y. et al. Conditional telomerase induction causes proliferation of hair follicle stem cells. Nature 436, 1048–1052 (2005)

    ADS  CAS  PubMed  PubMed Central  Google Scholar 

  70. 70

    Kim, N. W. et al. Specific association of human telomerase activity with immortal cells and cancer. Science 266, 2011–2015 (1994)

    ADS  CAS  Google Scholar 

  71. 71

    Counter, C. M., Hirte, H. W., Bacchetti, S. & Harley, C. B. Telomerase activity in human ovarian carcinoma. Proc. Natl Acad. Sci. USA 91, 2900–2904 (1994)

    ADS  CAS  PubMed  Google Scholar 

  72. 72

    Bryan, T. M. et al. Evidence for an alternative mechanism for maintaining telomere length in human tumors and tumor-derived cell lines. Nature Med. 3, 1271–1274 (1997)

    CAS  PubMed  PubMed Central  Google Scholar 

  73. 73

    Blanco, R., Muñoz, P., Klatt, P., Flores, J. M. & Blasco, M. A. Telomerase abrogation dramatically accelerates TRF2-induced epithelial carcinogenesis. Genes Dev. 21, 206–220 (2007)

    CAS  PubMed  PubMed Central  Google Scholar 

  74. 74

    Ohsumi, Y. Molecular dissection of autophagy: two ubiquitin-like systems. Nature Rev. Mol. Cell Biol. 2, 211–216 (2001)

    CAS  Google Scholar 

  75. 75

    Liang, X. H. et al. Induction of autophagy and inhibition of tumorigenesis by beclin 1. Nature 402, 672–676 (1999)

    ADS  CAS  Google Scholar 

  76. 76

    Yue, Z., Jin, S., Yang, C., Levine, A. J. & Heintz, N. Beclin 1, an autophagy gene essential for early embryonic development, is a haploinsufficient tumor suppressor. Proc. Natl Acad. Sci. USA 100, 15077–15082 (2003)

    ADS  CAS  PubMed  Google Scholar 

  77. 77

    Qu, X. et al. Promotion of tumorigenesis by heterozygous disruption of the beclin 1 autophagy gene. J. Clin. Invest. 112, 1809–1820 (2003)

    CAS  PubMed  PubMed Central  Google Scholar 

  78. 78

    Kondo, Y. & Kondo, S. Autophagy and cancer therapy. Autophagy 2, 85–90 (2006)

    PubMed  PubMed Central  Google Scholar 

  79. 79

    Kuma, A. et al. The role of autophagy during the early neonatal starvation period. Nature 432, 1032–1036 (2004)

    ADS  CAS  PubMed  Google Scholar 

  80. 80

    Komatsu, M. et al. Loss of autophagy in the central nervous system causes neurodegeneration in mice. Nature 441, 880–884 (2006)

    ADS  CAS  PubMed  Google Scholar 

  81. 81

    Hara, T. et al. Suppression of basal autophagy in neural cells causes neurodegenerative disease in mice. Nature 441, 885–889 (2006)

    ADS  CAS  PubMed  Google Scholar 

  82. 82

    Melendez, A. et al. Autophagy genes are essential for dauer development and lifespan extension in C. elegans. Science 301, 1387–1391 (2003)

    ADS  CAS  PubMed  Google Scholar 

  83. 83

    Bensaad, K. et al. TIGAR, a p53-inducible regulator of glycolysis and apoptosis. Cell 126, 107–120 (2006)

    CAS  PubMed  Google Scholar 

  84. 84

    Matoba, S. et al. p53 regulates mitochondrial respiration. Science 312, 1650–1653 (2006)

    ADS  CAS  PubMed  Google Scholar 

  85. 85

    Sabatini, D. M. mTOR and cancer: insights into a complex relationship. Nature Rev. Cancer 6, 729–734 (2006)

    CAS  Google Scholar 

  86. 86

    Wullschleger, S., Loewith, R. & Hall, M. N. TOR signaling in growth and metabolism. Cell 124, 471–484 (2006)

    CAS  PubMed  Google Scholar 

  87. 87

    Vellai, T. et al. Genetics: influence of TOR kinase on lifespan in C. elegans. Nature 426, 620 (2003)

    ADS  CAS  PubMed  Google Scholar 

  88. 88

    Kapahi, P. et al. Regulation of lifespan in Drosophila by modulation of genes in the TOR signaling pathway. Curr. Biol. 14, 885–890 (2004)

    CAS  PubMed  PubMed Central  Google Scholar 

  89. 89

    Kaeberlein, M. et al. Regulation of yeast replicative life span by TOR and Sch9 in response to nutrients. Science 310, 1193–1196 (2005)

    ADS  CAS  PubMed  Google Scholar 

  90. 90

    Schieke, S. M. et al. The mammalian target of rapamycin (mTOR) pathway regulates mitochondrial oxygen consumption and oxidative capacity. J. Biol. Chem. 281, 27643–27652 (2006)

    CAS  Google Scholar 

  91. 91

    Murphy, C. T. The search for DAF-16/FOXO transcriptional targets: approaches and discoveries. Exp. Gerontol. 41, 910–921 (2006)

    CAS  PubMed  Google Scholar 

  92. 92

    Hu, M. C. et al. IκB kinase promotes tumorigenesis through inhibition of forkhead FOXO3a. Cell 117, 225–237 (2004)

    CAS  PubMed  Google Scholar 

  93. 93

    Paik, J. H. et al. FoxOs are lineage-restricted redundant tumor suppressors and regulate endothelial cell homeostasis. Cell 128, 309–323 (2007)

    CAS  PubMed  PubMed Central  Google Scholar 

  94. 94

    Tothova, Z. et al. FoxOs are critical mediators of hematopoietic stem cell resistance to physiologic oxidative stress. Cell 128, 325–339 (2007)

    CAS  PubMed  Google Scholar 

  95. 95

    Baysal, B. E. et al. Mutations in SDHD, a mitochondrial complex II gene, in hereditary paraganglioma. Science 287, 848–851 (2000)

    ADS  CAS  Google Scholar 

  96. 96

    King, A., Selak, M. A. & Gottlieb, E. Succinate dehydrogenase and fumarate hydratase: linking mitochondrial dysfunction and cancer. Oncogene 25, 4675–4682 (2006)

    CAS  PubMed  Google Scholar 

  97. 97

    Ishii, N. et al. A mutation in succinate dehydrogenase cytochrome b causes oxidative stress and ageing in nematodes. Nature 394, 694–697 (1998)

    ADS  CAS  PubMed  Google Scholar 

  98. 98

    Walker, D. W. et al. Hypersensitivity to oxygen and shortened lifespan in a Drosophila mitochondrial complex II mutant. Proc. Natl Acad. Sci. USA 103, 16382–16387 (2006)

    ADS  CAS  PubMed  Google Scholar 

  99. 99

    Dillin, A. et al. Rates of behavior and aging specified by mitochondrial function during development. Science 298, 2398–2401 (2002)

    ADS  CAS  PubMed  PubMed Central  Google Scholar 

  100. 100

    Lee, S. S. et al. A systematic RNAi screen identifies a critical role for mitochondria in C. elegans longevity. Nature Genet. 33, 40–48 (2003)

    CAS  PubMed  Google Scholar 

  101. 101

    Levine, A. J., Feng, Z., Mak, T. W., You, H. & Jin, S. Coordination and communication between the p53 and IGF-1-AKT-TOR signal transduction pathways. Genes Dev. 20, 267–275 (2006)

    CAS  PubMed  Google Scholar 

Download references


We thank members of our laboratory for helpful discussions and I. Rovira for help with the manuscript. This work was supported by grants from the NIH Intramural program and Ellison Medical Foundation (T.F.), the Spanish Ministry of Education and Science (M.S., M.A.B.), the European Union (M.S., M.A.B.) and the Josef Steiner Award (M.A.B.).

Author information



Corresponding author

Correspondence to Toren Finkel.

Ethics declarations

Competing interests

Reprints and permissions information is available at The authors declare no competing financial interests.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

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

Download citation

Further reading


By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.


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