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.

  • Letter
  • Published:

A stress-sensitive reporter predicts longevity in isogenic populations of Caenorhabditis elegans

Nature Genetics volume 37, pages 894–898 (2005)Cite this article

Abstract

When both genotype and environment are held constant, 'chance' variation in the lifespan of individuals in a population is still quite large. Using isogenic populations of the nematode Caenorhabditis elegans, we show that, on the first day of adult life, chance variation in the level of induction of a green fluorescent protein (GFP) reporter coupled to a promoter from the gene hsp-16.2 predicts as much as a fourfold variation in subsequent survival. The same reporter is also a predictor of ability to withstand a subsequent lethal thermal stress. The level of induction of GFP is not heritable, and GFP expression levels in other reporter constructs are not associated with differences in longevity. HSP-16.2 itself is probably not responsible for the observed differences in survival but instead probably reflects a hidden, heterogeneous, but now quantifiable, physiological state that dictates the ability of an organism to deal with the rigors of living.

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: Overview.
Figure 2: Survival and thermotolerance of worms previously sorted on differential hsp-16.2::GFP expression after a 2-h heat shock.
Figure 3: Survival of worms previously sorted on differential hsp-16.2::GFP expression after 1 h of induction at 35 °C.

Similar content being viewed by others

Accession codes

Accessions

GenBank/EMBL/DDBJ

References

  1. Finch, C.E. & Kirkwood, T.B. Chance, Development and Aging (Oxford University Press, London, 2000).

    Google Scholar 

  2. Kirkwood, T.B. & Finch, C.E. Ageing: the old worm turns more slowly. Nature 419, 794–795 (2002).

    Article  CAS  PubMed  Google Scholar 

  3. Finch, C.E. & Tanzi, R.E. Genetics of aging. Science 278, 407–411 (1997).

    Article  CAS  PubMed  Google Scholar 

  4. Johnson, T.E. Increased life-span of age-1 mutants in Caenorhabditis elegans and lower Gompertz rate of aging. Science 249, 908–912 (1990).

    Article  CAS  PubMed  Google Scholar 

  5. Johnson, T.E. et al. Gerontogenes mediate health and longevity in nematodes through increasing resistance to environmental toxins and stressors. Exp. Gerontol. 35, 687–694 (2000).

    Article  CAS  PubMed  Google Scholar 

  6. Vaupel, J.W. et al. Biodemographic trajectories of longevity. Science 280, 855–860 (1998).

    Article  CAS  PubMed  Google Scholar 

  7. Kenyon, C. Ponce d'elegans: genetic quest for the fountain of youth. Cell 84, 501–504 (1996).

    Article  CAS  PubMed  Google Scholar 

  8. Link, C.D., Cypser, J.R., Johnson, C.J. & Johnson, T.E. Direct observation of stress response in Caenorhabditis elegans using a reporter transgene. Cell Stress Chaperones 4, 235–242 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Cypser, J.R. & Johnson, T.E. Multiple stressors in Caenorhabditis elegans induce stress hormesis and extended longevity. J. Gerontol. A Biol. Sci. Med. Sci. 57, B109–B114 (2002).

    Article  PubMed  Google Scholar 

  10. Calabrese, E.J. & Baldwin, L.A. Defining hormesis. Hum. Exp. Toxicol. 21, 91–97 (2002).

    Article  CAS  PubMed  Google Scholar 

  11. 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  PubMed  PubMed Central  Google Scholar 

  12. Kelly, W.G., Xu, S., Montgomery, M.K. & Fire, A. Distinct requirements for somatic and germline expression of a generally expressed Caernorhabditis elegans gene. Genetics 146, 227–238 (1997).

    CAS  PubMed  PubMed Central  Google Scholar 

  13. Elowitz, M.B., Levine, A.J., Siggia, E.D. & Swain, P.S. Stochastic gene expression in a single cell. Science 297, 1183–1186 (2002).

    Article  CAS  PubMed  Google Scholar 

  14. Raser, J.M. & O'Shea, E.K. Control of stochasticity in eukaryotic gene expression. Science 304, 1811–1814 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Brenner, S. The genetics of Caenorhabditis elegans. Genetics 77, 71–94 (1974).

    CAS  PubMed  PubMed Central  Google Scholar 

  16. Johnson, T.E. & Wood, W.B. Genetic analysis of life-span in Caenorhabditis elegans. Proc. Natl. Acad. Sci. USA 79, 6603–6607 (1982).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Herskind, A.M. et al. The heritability of human longevity: a population-based study of 2872 Danish twin pairs born 1870–1900. Hum. Genet. 97, 319–323 (1996).

    Article  CAS  PubMed  Google Scholar 

  18. Gillooly, J.F., Brown, J.H., West, G.B., Savage, V.M. & Charnov, E.L. Effects of size and temperature on metabolic rate. Science 293, 2248–2251 (2001).

    Article  CAS  PubMed  Google Scholar 

  19. McAdams, H.H. & Arkin, A. It's a noisy business! Genetic regulation at the nanomolar scale. Trends Genet. 15, 65–69 (1999).

    Article  CAS  PubMed  Google Scholar 

  20. Strehler, B.L. & Mildivan, A.S. General theory of mortality and aging. Science 132, 14–21 (1960).

    Article  CAS  PubMed  Google Scholar 

  21. Kirkwood, T.B. et al. What accounts for the wide variation in life span of genetically identical organisms reared in a constant environment? Mech. Ageing Dev. 126, 439–443 (2005).

    Article  PubMed  Google Scholar 

  22. Melov, S., Lithgow, G.J., Fischer, D.R., Tedesco, P.M. & Johnson, T.E. Increased frequency of deletions in the mitochondrial genome with age of Caenorhabditis elegans. Nucleic Acids Res. 23, 1419–1425 (1995).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Golden, T.R. & Melov, S. Microarray analysis of gene expression with age in individual nematodes. Aging Cell 3, 111–124 (2004).

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  25. Fedoroff, N. & Fontana, W. Genetic networks. Small numbers of big molecules. Science 297, 1129–1131 (2002).

    Article  CAS  PubMed  Google Scholar 

  26. Klass, M.R. Aging in the nematode Caenorhabditis elegans: major biological and environmental factors influencing life span. Mech. Ageing Dev. 6, 413–429 (1977).

    Article  CAS  PubMed  Google Scholar 

  27. Rao, C.V., Wolf, D.M. & Arkin, A.P. Control, exploitation and tolerance of intracellular noise. Nature 420, 231–237 (2002).

    Article  CAS  PubMed  Google Scholar 

  28. Baker, G.T. III & Sprott, R.L. Biomarkers of aging. Exp. Gerontol. 23, 223–239 (1988).

    Article  PubMed  Google Scholar 

  29. Walker, G.A. & Lithgow, G.J. Lifespan extension in C. elegans by a molecular chaperone dependent upon insulin-like signals. Aging Cell 2, 131–139 (2003).

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We thank members of the laboratory of T.E.J., especially C. Link and S. Henderson, for comments and support; G. Amdam for insight into control theory; and A. Smith for help. Support for this work was provided by the US National Institutes of Health (to J.W.V. and to T.E.J.) and by a Polis Foundation Grant (to S.L.R.).

Author information

Author notes

  1. Shane L Rea and Deqing Wu: These authors contributed equally to this work.

Authors and Affiliations

  1. Institute for Behavioral Genetics, University of Colorado at Boulder, Box 447, Boulder, 80309, Colorado, USA

    Shane L Rea, Deqing Wu, James R Cypser & Thomas E Johnson

  2. Max Planck Institute for Demographic Research, Konrad-Zuse-Strasse 1, Rostock, D-18057, Germany

    James W Vaupel

  3. Department of Integrative Biology, University of Colorado at Boulder, Box 447, Boulder, 80309, Colorado, USA

    Thomas E Johnson

Authors
  1. Shane L Rea
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Deqing Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. James R Cypser
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. James W Vaupel
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Thomas E Johnson
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Thomas E Johnson.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Supplementary information

Supplementary Fig. 1

Western analysis. (PDF 766 kb)

Supplementary Fig. 2

HSP-16::GFP expression in individual worms. (PDF 833 kb)

Supplementary Fig. 3

Differential expression of MTL-2::GFP. (PDF 638 kb)

Supplementary Table 1

Mean lifespan — selected longevity. (PDF 9 kb)

Supplementary Table 2

Mean lifespan — all longevity. (PDF 9 kb)

Supplementary Table 3

Mean survival. (PDF 7 kb)

Supplementary Table 4

P value for log rank test. (PDF 5 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Rea, S., Wu, D., Cypser, J. et al. A stress-sensitive reporter predicts longevity in isogenic populations of Caenorhabditis elegans. Nat Genet 37, 894–898 (2005). https://doi.org/10.1038/ng1608

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ng1608

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