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Roundworms: Caenorhabditis Elegans - Stress, Biomarkers, And Molecular Changes

age aging genetic life mutants age johnson

Nematodes show many of the same signs of aging that are seen in humans. They accumulate a fluorescent pigment in their cells that is called lipofuscin. They move slower and slower and finally stop moving altogether a few days before they die. They eat less and less (and defecate less and less too), as they near death. They get wrinkled. They show a lot of other pathological changes associated with aging. However, all tissues do not change at the same rate. The gonad changes quite rapidly but neurological tissue seems to remain quite intact.

Among the most consistent changes associated with increased longevity of the mutants is the increased resistance to many forms of environmental stress (see Figure 3). Johnson’s lab has found that heat, UV, reactive oxidants, etc. are all less toxic to the long-lived mutants. Although not all agree, it seems likely that the increased stress resistance plays a key role in the life prolongation of these mutants. Indeed, the Figure 2 Effect of age-1 on survival SOURCE: Adapted from: Melov, S., et al. “Extension of Life-Span with Superoxide Dismutase/Catalase Mimetics.” Science 289: (2000): 1567-1569. drug that prolonged life in the worms was an antioxidant designed to mimic the effect of a normal protein found at higher levels in age-1 mutants. This is a very exciting and extremely competitive area of research but may well yield secrets that will result in doubling the human life span within the life times of our children, if not ourselves.

THOMAS E. JOHNSON

BIBLIOGRAPHY

Brenner, S. ‘‘The Genetics of Caenorhabditis Elegans.’’ Genetics 77 (1974): 71–94.

Friedman, D. B., and Johnson, T. E. ‘‘A Mutation in the Age-1 Gene in Caenorhabditis Elegans Lengthens Life and Reduces Hermaphrodite Fertility.’’ Genetics 118 (1988): 75–86.

Johnson, F. B.; Sinclair, D. A.; and Guarante, L. ‘‘Molecular Biology of Aging.’’ Cell 96 (1999): 291–302.

Johnson, T. E. ‘‘The Increased Life Span of Age-1 Mutants in Caenorhabditis Elegans Results from Lowering the Gompertz Rate of Aging.’’ Science 249 (1990): 908–912.

Johnson, T. E., and Wood, W. B. ‘‘Genetic Analysis of the Life-Span of Caenorhabditis Elegans.’’ Proceedings of the National Academy of Sciences USA 79 (1982): 6603–6607.

Klass, M. R. ‘‘A Method for the Isolation of Longevity Mutants in the Nematode Caenorhabditis Elegans and Initial Results.’’ Mechanisms of Ageing and Development 22 (1983): 279–286.

Martin, G. M.; Austad, S. N.; and Johnson, T. E. ‘‘Genetic Analysis of Aging: Role of Oxidative Damage and Environmental Stresses.’’ Nature Genetics 13 (1996): 25–34.

Riddle, D. L.; Blumenthal, T.; Meyer, B. J.; and Priess, J. R. C. elegans II. Cold Spring Harbor, N.Y.: Cold Spring Harbor Press, 1997.

Wood, W. B., ed. The Biology of Caenorhabditis elegans. Cold Spring Harbor, N.Y.: Cold Spring Harbor Press, 1988.

Figure 3 Survival curves of two wild-type age strains, an age mutant strain, and a heterozygous strain of C. elegans. SOURCE: Adapted from: Johnson, T. E. “Increased Life-Span of Age-1 Mutants in Caernobditis elegans and Lower Gompertz Rate of Aging.”. Science 249 (1990): 908-913.

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