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Towards an e-biology of ageing: integrating theory and data

Nature Reviews Molecular Cell Biology volume 4, pages 243–249 (2003)Cite this article

Abstract

Ageing is a highly complex process; it involves interactions between numerous biochemical and cellular mechanisms that affect many tissues in an organism. Although work on the biology of ageing is now advancing quickly, this inherent complexity means that information remains highly fragmented. We describe how a new web-based modelling initiative is seeking to integrate data and hypotheses from diverse biological sources.

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Figure 1: The sequential development of ageing mechanisms.
Figure 2: Organizational scheme for the BASIS project.
Figure 3: Stochastic modelling of cell replicative senescence.

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References

  1. Kirkwood, T. B. L. & Austad, S. N. Why do we age? Nature 408, 233–238 (2000).

    Article  CAS  Google Scholar 

  2. Kirkwood, T. B. L. Evolution of ageing. Nature 270, 301–304 (1977).

    Article  CAS  Google Scholar 

  3. Finch, C. E. & Kirkwood, T. B. L. Chance, Development and Aging (Oxford Univ. Press, New York, 2000).

    Google Scholar 

  4. Herndon, L. A. et al. Stochastic and genetic factors influence tissue-specific decline in ageing C. elegans. Nature 419, 808–814 (2002).

    Article  CAS  Google Scholar 

  5. Kirkwood, T. B. L. & Finch, C. E. The old worm turns more slowly. Nature 419, 794–795 (2002).

    Article  CAS  Google Scholar 

  6. Kowald, A. & Kirkwood, T. B. L. Mitochondrial mutations, cellular instability and ageing: modelling the population dynamics of mitochondria. Mutat. Res. 295, 93–103 (1993).

    Article  CAS  Google Scholar 

  7. Kowald, A. & Kirkwood, T. B. L. A network theory of ageing: the interactions of defective mitochondria, aberrant proteins, free radicals and scavengers in the ageing process. Mutat. Res. 316, 209–236 (1996).

    Article  CAS  Google Scholar 

  8. Kirkwood, T. B. L & Kowald, A. Network theory of ageing. Exp. Gerontol. 32, 395–399 (1997).

    Article  CAS  Google Scholar 

  9. Sozou, P. D. & Kirkwood, T. B. L. A stochastic network model of cell replicative senescence based on telomere shortening, oxidative stress and somatic mutations in nuclear and mitochondrial DNA. J. Theor. Biol. 213, 573–586 (2001).

    Article  CAS  Google Scholar 

  10. Proctor, C. & Kirkwood, T. B. L. Modelling telomere shortening and the role of oxidative stress. Mech. Ageing Dev. 123, 351–363 (2002).

    Article  CAS  Google Scholar 

  11. Szilard, L. On the nature of the aging process. Proc. Natl Acad. Sci. USA 45, 35–45 (1959).

    Article  Google Scholar 

  12. Orgel, L. E. The maintenance of the accuracy of protein synthesis and its relevance to ageing. Proc. Natl Acad. Sci. USA 49, 517–521 (1963).

    Article  CAS  Google Scholar 

  13. Kacser, H. & Burns, J. A. The control of flux. Symp. Soc. Exp. Biol. 7, 65–104 (1973).

    Google Scholar 

  14. Kacser, H. & Burns, J. A. Molecular democracy: who shares the controls? Biochem. Soc. Trans. 7, 1149–1160 (1979).

    Article  CAS  Google Scholar 

  15. Letellier, T, et al. Metabolic control analysis and mitochondrial pathologies. Mol. Cell. Biochem. 184, 409–417 (1998).

    Article  CAS  Google Scholar 

  16. Ainscow, E. K. & Brand, M. D. Top-down control analysis of ATP turnover, glycolysis and oxidative phosphorylation in rat hepatocytes. Eur. J. Biochem. 263, 671–685 (1999).

    Article  CAS  Google Scholar 

  17. Murphy, M. P. How understanding the control of energy metabolism can help investigation of mitochondrial dysfunction, regulation and pharmacology. Biochem. Biophys. Acta. 1504, 1–11 (2001).

    CAS  PubMed  Google Scholar 

  18. Hofmeyr, J. S. & Westerhoff, H. V. Building the cellular puzzle: control in multi-level reaction networks. J. Theor. Biol. 208, 261–285 (2001).

    Article  CAS  Google Scholar 

  19. Orr, W. C. & Sohal, R. Extension of life span by overexpression of superoxide dismutase and catalase in Drosophila melanogaster. Science 263, 1128–1130 (1994).

    Article  CAS  Google Scholar 

  20. Jazwinski, S. M. Metabolic mechanisms of yeast ageing. Exp. Gerontol. 35, 671–676 (2000).

    Article  CAS  Google Scholar 

  21. Lithgow, G. J. Aging mechanisms from nematodes to mammals. Nutrition 14, 522–524 (1998).

    Article  CAS  Google Scholar 

  22. Larsen, P. L. Asking the age-old questions. Nature Genet. 28, 102–104 (2001).

    Article  CAS  Google Scholar 

  23. Gems, D. & Partridge, L. Insulin/IGF signalling and ageing: seeing the bigger picture. Curr. Opin. Genet. Dev. 11, 287–292 (2001).

    Article  CAS  Google Scholar 

  24. Cournil, A. & Kirkwood, T. B. L. If you would live long, choose your parents well. Trends Genet. 17, 233–235 (2001).

    Article  CAS  Google Scholar 

  25. McAdams, H. H. & Arkin, A. Stochastic mechanisms in gene expression. Proc. Natl Acad. Sci. USA 94, 814–819 (1997).

    Article  CAS  Google Scholar 

  26. Kowald, A. & Kirkwood, T. B. L. Accumulation of defective mitochondria through delayed degradation of damaged organelles and its possible role in the ageing of post-mitotic and dividing cells. J. Theor. Biol. 202, 145–160 (2000).

    Article  CAS  Google Scholar 

  27. Cortopassi, G. A., Shibata, D., Soong N. W. & Arnheim, N. A pattern of accumulation of a somatic deletion of mitochondrial-DNA in aging human tissues. Proc. Natl Acad. Sci. USA 89, 7370–7374 (1992).

    Article  CAS  Google Scholar 

  28. Lee, C. M., Pang, C. Y., Hsu, H. S. & Wei, Y. H. Differential accumulation of 4977 bp deletion in mitochondrial DNA of various tissues in human ageing. Biochim. Biophys. Acta. 1226, 37–43 (1994).

    Article  CAS  Google Scholar 

  29. von Zglinicki, T., Bürkle, A. & Kirkwood, T. B. L. Stress, DNA damage and ageing — an integrative approach. Exp. Gerontol. 36, 1049–1062 (2001).

    Article  CAS  Google Scholar 

  30. Holliday, R., Huschtscha, L. I., Tarrant, G. M. & Kirkwood, T. B. L. Testing the commitment theory of cellular ageing. Science 198, 366–372 (1977).

    Article  CAS  Google Scholar 

  31. Smith, J. R. & Whitney, R. G. Intraclonal variation in proliferative potential of human diploid fibroblast cells: stochastic mechanism for cellular aging. Science 207, 82–84 (1980).

    Article  CAS  Google Scholar 

  32. Campisi, J. From cells to organisms: can we learn about aging from cells in culture? Exp. Gerontol. 36, 607–618 (2001).

    Article  CAS  Google Scholar 

  33. Loeffler, M. et al. Somatic mutation, monoclonality and stochastic models of stem cell organization in the intestinal crypt. J. Theor. Biol. 160, 471–491 (1993).

    Article  CAS  Google Scholar 

  34. Martin, K., Kirkwood, T. B. L. & Potten, C. S. Age changes in stem cells of murine small intestinal crypts. Exp. Cell Res. 241, 316–323 (1998).

    Article  CAS  Google Scholar 

  35. Martin, K., Potten, C. S., Roberts, S. A. & Kirkwood, T. B. L. Altered stem cell regeneration in irradiated intestinal crypts of senescent mice. J. Cell Sci. 111, 2297–2303 (1998).

    CAS  PubMed  Google Scholar 

  36. Martin, K., Potten, C. S. & Kirkwood, T. B. L. Age-related changes in irradiation-induced apoptosis and expression of p21 and p53 in crypt stem cells of murine intestine. Ann. NY Acad. Sci. 908, 315–318 (2000).

    Article  CAS  Google Scholar 

  37. Harbinder, S. et al. Genetically targeted cell disruption in Caenorhabditis elegans. Proc. Natl Acad. Sci. USA 94, 13128–13133 (1997).

    Article  CAS  Google Scholar 

  38. Arantes-Oliveira, N., Apfeld, J., Dillin, A. & Kenyon, C. Regulation of life-span by germ-line stem cells in Caenorhabditis elegans. Science 295, 502–505 (2002).

    CAS  PubMed  Google Scholar 

  39. Alliance for Cellular Signaling. Overview of the Alliance for Cellular Signaling. Nature 420, 703–706 (2002).

  40. Wolpert, L. The Unnatural Nature of Science 135–136 (Faber and Faber, London, 1992).

    Google Scholar 

  41. Editorial. Nature 417, 471 (2002).

  42. Medawar, P. B. An Unsolved Problem of Biology (H. K. Lewis, London, 1952).

    Google Scholar 

  43. Harman, D. Aging: a theory based on free radical and radiation chemistry. J. Gerontol. 11, 298–300 (1956).

    Article  CAS  Google Scholar 

  44. Williams, G. C. Pleiotropy, natural selection and the evolution of senescence. Evolution 11, 398–411 (1957).

    Article  Google Scholar 

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

    Article  CAS  Google Scholar 

  46. Friedman, D. B. & Johnson, T. E. Three mutants that extend both mean and maximum life-span of the nematode, Caenorhabditis elegans, define the age-1 gene. J. Gerontol. 43, B102–B109 (1988).

    Article  CAS  Google Scholar 

  47. Kirkwood, T. B. L. & Franceschi, C. Is aging as complex as it would appear? Ann. NY Acad. Sci. 663, 412–417 (1992).

    Article  CAS  Google Scholar 

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Acknowledgements

The BASIS project is funded by the UK Biotechnology and Biological Sciences Research Council, Medical Research Council and Department of Trade and Industry. Our work is also funded by the BBSRC Science of Ageing initiative.

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Authors and Affiliations

  1. the Institute for Ageing and Heath, University of Newcastle, Newcastle General Hospital, Newcastle upon Tyne, NE4 6BE, UK

    Thomas B.L. Kirkwood, Colin S. Gillespie, Carole J. Proctor & Daryl P. Shanley

  2. the School of Mathematics and Statistics, University of Newcastle, Newcastle upon Tyne, NE1 7RU, UK

    Richard J. Boys & Darren J. Wilkinson

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  1. Thomas B.L. Kirkwood
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Correspondence to Thomas B.L. Kirkwood.

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FURTHER INFORMATION

Thomas B. L. Kirkwood's laboratory

BASIS project

Systems biology markup language

e-science initiative

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Kirkwood, T., Boys, R., Gillespie, C. et al. Towards an e-biology of ageing: integrating theory and data. Nat Rev Mol Cell Biol 4, 243–249 (2003). https://doi.org/10.1038/nrm1051

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