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Long lifespan in worms with long telomeric DNA

A Corrigendum to this article was published on 01 January 2005

Abstract

Telomere length is a crucial factor in senescence1,2,3, but it has not been determined whether animals with long telomeres live longer than those with normal-length telomeres in the isogenic background of a given species. Here we show the effect of long telomeres on lifespan in the nematode Caenorhabditis elegans. We examined the effect of telomere length on lifespan by overexpressing HRP-1, a telomere-binding protein, which gradually increased telomere length in worms. Worms with longer telomeres lived longer. We confirmed that the extension of lifespan was due to the increased telomere length, and not to the overexpression of HRP-1 per se, by examining the lifespans of nontransgenic progeny of the transgenic worms, who retained the longer telomeres. The lifespan-extending effect of long telomeres was dependent on daf-16. The number of germ stem cells was not affected in worms with long telomeres, indicating that the telomere effect on lifespan is independent of germ stem cell cycling. Worms with long telomeres were more resistant to heat stress. Taken together, our results suggest that signaling may be initiated in postmitotic somatic cells by telomere length to regulate organismal lifespan.

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Figure 1: Identification and characterization of a single-stranded telomeric DNA binding protein, HRP-1, in C. elegans.
Figure 2: Overexpression of HRP-1 increases telomere length.
Figure 3: Worms with lengthened telomeric DNA have extended lifespan.
Figure 4: Worms with extended telomeric DNA have greater resistance to heat shock, and this effect is dependent on daf-16.

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References

  1. Krupp, G., Klapper, W. & Parwaresch, R. Cell proliferation, carcinogenesis and diverse mechanisms of telomerase regulation. Cell Mol. Life Sci. 57, 464–486 (2000).

    Article  CAS  Google Scholar 

  2. Morin, G.B. Telomere control of replicative lifespan. Exp. Gerontol. 32, 375–382 (1997).

    Article  CAS  Google Scholar 

  3. Harley, C.B., Vaziri, H., Counter, C.M. & Allsopp, R.C. The telomere hypothesis of cellular aging. Exp. Gerontol. 27, 375–382 (1992).

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  6. Hemann, M.T. & Greider, C.W. Wild-derived inbred mouse strains have short telomeres. Nucleic Acids Res. 28, 4474–447 (2000).

    Article  CAS  Google Scholar 

  7. Wicky, C. et al. Telomeric repeats (TTAGGC)n are sufficient for chromosome capping function in Caenorhabditis elegans. Proc. Natl. Acad. Sci. USA 93, 8983–8988 (1996).

    Article  CAS  Google Scholar 

  8. Lin, J.J. & Zakian, V.A. Isolation and characterization of two Saccharomyces cerevisiae genes that encode proteins that bind to (TG1-3)n single strand telomeric DNA in vitro. Nucleic Acids Res. 22, 4906–4913 (1994).

    Article  CAS  Google Scholar 

  9. LaBranche, H. et al. Telomere elongation by hnRNP A1 and a derivative that interacts with telomeric repeats and telomerase. Nat. Genet. 19, 199–202 (1998).

    Article  CAS  Google Scholar 

  10. Fiset, S. & Chabot, B. hnRNP A1 may interact simultaneously with telomeric DNA and the human telomerase RNA in vitro. Nucleic Acids Res. 29, 2268–2275 (2001).

    Article  CAS  Google Scholar 

  11. Ketting, R.F., Haverkamp, T.H., van Luenen, H.G. & Plasterk, R.H. Mut-7 of C. elegans, required for transposon silencing and RNA interference, is a homolog of Werner syndrome helicase and RNaseD. Cell 99, 133–141 (1999).

    Article  CAS  Google Scholar 

  12. Lithgow, G.J., White, T.M., Hinerfeld, D.A. & Johnson, T.E. Thermotolerance of a long-lived mutant of Caenorhabditis elegans. J. Gerontol. 49, B270–276 (1994).

    Article  CAS  Google Scholar 

  13. Lithgow, G.J., White, T.M., Melov, S. & Johnson, T.E. Thermotolerance and extended life-span conferred by single-gene mutations and induced by thermal stress. Proc. Natl. Acad. Sci. USA 92, 7540–7544 (1995).

    Article  CAS  Google Scholar 

  14. Honda, Y. & Honda, S. The daf-2 gene network for longevity regulates oxidative stress resistance and Mn-superoxide dismutase gene expression in Caenorhabditis elegans. FASEB J. 13, 1385–1393 (1999).

    Article  CAS  Google Scholar 

  15. Larsen, P.L. Aging and resistance to oxidative damage in Caenorhabditis elegans. Proc. Natl. Acad. Sci. USA 90, 8905–8909 (1993).

    Article  CAS  Google Scholar 

  16. Lin, K., Dorman, J.B., Rodan, A. & Kenyon, C. daf-16: An HNF-3/forkhead family member that can function to double the life-span of Caenorhabditis elegans. Science 278, 1319–1322 (1997).

    Article  CAS  Google Scholar 

  17. Ogg, S. et al. The Fork head transcription factor DAF-16 transduces insulin-like metabolic and longevity signals in C. elegans. Nature 389, 994–999 (1997).

    Article  CAS  Google Scholar 

  18. Lin, K., Hsin, H., Libina, N. & Kenyon, C. Regulation of the Caenorhabditis elegans longevity protein DAF-16 by insulin/IGF-1 and germline signaling. Nat. Genet. 28, 139–145 (2001).

    Article  CAS  Google Scholar 

  19. Hsin, H. & Kenyon, C. Signals from the reproductive system regulate the lifespan of C. elegans. Nature 399, 362–366 (1999).

    Article  CAS  Google Scholar 

  20. Benard, C. et al. The C. elegans maternal-effect gene clk-2 is essential for embryonic development, encodes a protein homologous to yeast Tel2p and affects telomere length. Development 128, 4045–4055 (2001).

    CAS  PubMed  Google Scholar 

  21. Lim, C.S., Mian, I.S., Dernburg, A.F. & Campisi, J. C. elegans clk-2, a gene that limits life span, encodes a telomere length regulator similar to yeast telomere binding protein Tel2p. Curr. Biol. 11, 1706–1710 (2001).

    Article  CAS  Google Scholar 

  22. Ahmed, S., Alpi, A., Hengartner, M.O. & Gartner, A. C. elegans RAD-5/CLK-2 defines a new DNA damage checkpoint protein. Curr. Biol. 11, 1934–194. (2001).

    Article  CAS  Google Scholar 

  23. Benard, C. & Hekimi, S. Long-lived mutants, the rate of aging, telomeres and the germline in Caenorhabditis elegans. Mech. Ageing Dev. 123, 869–880 (2002).

    Article  CAS  Google Scholar 

  24. Cawthon, R.M., Smith, K.R., O'Brien, E., Sivatchenko, A. & Kerber, R.A. Association between telomere length in blood and mortality in people aged 60 years or older. Lancet 361, 393–395 (2003).

    Article  CAS  Google Scholar 

  25. Kwon, J.Y. et al. Caenorhabditis elegans mediator complexes are required for developmental-specific transcriptional activation. Proc. Natl. Acad. Sci. USA 96, 14990–14995 (1999).

    Article  CAS  Google Scholar 

  26. Mello, C.C., Kramer, J.M., Stinchcomb, D. & Ambros, V. Efficient gene transfer in C. elegans: extrachromosomal maintenance and integration of transforming sequences. EMBO J. 10, 3959–3970 (1991).

    Article  CAS  Google Scholar 

  27. Garigan, D. et al. Genetic analysis of tissue aging in Caenorhabditis elegans: a role for heat-shock factor and bacterial proliferation. Genetics 161, 1101–1112 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

We thank C. Kenyon for her comments and invaluable advice on this project, A. Fire for the vectors and CGC for the strains. This project was supported by the Molecular Aging Research Center Grant (HPEB, Korea).

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Correspondence to Junho Lee.

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Joeng, K., Song, E., Lee, KJ. et al. Long lifespan in worms with long telomeric DNA. Nat Genet 36, 607–611 (2004). https://doi.org/10.1038/ng1356

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