by the constancy of the coefficient of variation, consistent with the hypothesis that those inbred populations that die late in life do not fundamentally differ from those that die early. The biphasic mortality rate seen in the genetically heterogeneous populations of nematodes results from the genetic heterogeneity in the population. Genetic heterogeneity could explain similar mortality kinetics in human populations (Vaupel et al., 1979) in which, beyond 85 years, the mortality rate stops increasing exponentially and becomes constant, or actually decreases. Genetic heterogeneity could play a large role in the long period of ''flat" mortality rate increases separated by Carey et al. (1992).

Mortality Rates in Large Populations

The relationship between age-specific mortality rate and chronological age on a population of 180,000 worms has been modeled using an exponential function of chronological age (Brooks et al., 1994). Vaupel et al. (1994) used a two-stage Gompertz model and showed that two curves (each with exponential rates of increase) provided a significantly better fit. The break in the curves occurred at day 8, about the time the wild type stops reproducing. Clearly the "best" model for mortality in large populations of C. elegans does not fit a two-parameter Gompertz model.

Conclusions

It is clear that gerontogenes exist. Identification of these genes has been achieved in lower eukaryotes and in one metazoan, C. elegans. The most powerful approach, inducing single-gene mutants, may be too expensive to ever be pursued in mammals. QTL mapping offers a useful alternative to localizing genes, but cloning of the genes underlying these QTLs will be problematic. Mortality alterations that result from changes in these genes can be studied, and results from the Johnson laboratory suggest that much of the flattening of mortality rates at later ages in humans could result from genetic heterogeneity among individuals. Clearly such heterogeneity leads to an extended period of nonexponentially increases in age-specific mortality at the end of life.

References

Arking, R.. S.P. Dudas, and G.T. Baker III 1993  Genetic and environmental factors regulating the expression of an extended longevity phenotype in a long-lived strain of Drosophila. Genetica 91:127-142.


Botstein, D., and R. Mauer 1982  Genetic approaches to the analysis of microbial development. Annual Review of Genetics 16:61-83.

Brooks, A., and T.E. Johnson 1991  Genetic specification of life span and self-fertility in recombinant-inbred strains of Caenorhabditis elegans. Heredity 67:19-28.



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