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Stochastic and genetic factors influence tissue-specific decline in ageing C. elegans

Nature volume 419, pages 808–814 (2002)Cite this article

Abstract

The nematode Caenorhabditis elegans is an important model for studying the genetics of ageing, with over 50 life-extension mutations known so far. However, little is known about the pathobiology of ageing in this species, limiting attempts to connect genotype with senescent phenotype. Using ultrastructural analysis and visualization of specific cell types with green fluorescent protein, we examined cell integrity in different tissues as the animal ages. We report remarkable preservation of the nervous system, even in advanced old age, in contrast to a gradual, progressive deterioration of muscle, resembling human sarcopenia. The age-1(hx546) mutation, which extends lifespan by 60–100%, delayed some, but not all, cellular biomarkers of ageing. Strikingly, we found strong evidence that stochastic as well as genetic factors are significant in C. elegans ageing, with extensive variability both among same-age animals and between cells of the same type within individuals.

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Figure 1: Behavioural phenotypes of ageing nematodes indicate progressive decline with stochastic onset and variable rates.
Figure 2: The integrity of the nervous system is maintained in ageing nematodes.
Figure 3: Age-related deterioration of C. elegans body wall muscle.
Figure 4: The long-lived age-1 mutant is not altered in age-related yolk protein redistribution but does exhibit delayed sarcopenia.

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Acknowledgements

We thank the following people for providing the following strains used in this study: B. Wadsworth for IM175, S. Clark for ZB154, R. Padgett for NW1099, A. Fire for PD4251, P. Hoppe and B. Waterston for RW1596, B. Grant for DH1033, I. Johnstone for IA019, E. Jorgensen for EG1653, and J. Plenefisch for rhIs2. We also thank the Caenorhabditis Genetics Center funded by NIH NCRR for the TJ1052 and BE13 strains. We thank G. Stephney, T. Stephney and K. Nguyen for help with electron microscopy; B. Levine and A. Melendez for helpful discussions about autophagy in C. elegans; G. Patterson and B. Grant for critical reading of this manuscript; and T. Johnson and D. Wu for advice about the analysis of behavioural class as a predictor of life expectancy. This work was supported by grants from the National Institute of Neurological Disorders and Stroke and the National Institute on Aging to M.D., and the Center for C. elegans Anatomy was supported by a grant from the NIH Division of Research Resources to D.H.

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  1. Department of Molecular Biology and Biochemistry, Rutgers, The State University of New Jersey, A232 Nelson Biological Laboratories, 604 Allison Road, Piscataway, New Jersey, 08854, USA

    Laura A. Herndon, Peter J. Schmeissner, Justyna M. Dudaronek, Paula A. Brown, Kristin M. Listner, Yuko Sakano & Monica Driscoll

  2. Department of Neuroscience, Albert Einstein College of Medicine, 1410 Pelham Parkway, Bronx, New York, 10461, USA

    Marie C. Paupard & David H. Hall

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Herndon, L., Schmeissner, P., Dudaronek, J. et al. Stochastic and genetic factors influence tissue-specific decline in ageing C. elegans. Nature 419, 808–814 (2002). https://doi.org/10.1038/nature01135

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