Age-specific demographic profiles of longevity mutants in Caenorhabditis elegans show segmental effects.
Demographic profiles of several single-gene longevity mutants of the nematode Caenorhabditis elegans reveal segmental (age-specific) effects on mortality. The mortality profiles of wild-type worms were examined across multiple replicate cultures containing 100,000 or more nematodes and found to be quite replicable, although clear environmental effects are routinely found. The combined profile of wild type was compared with those of three long-lived mutants to determine how age-specific mortality is altered by mutations in age-1, clk-1, or spe-26. In all four genotypes, death rates fit a two-stage Gompertz model better than a one-stage Gompertz; that is, mortality levels off at later ages. The largest genetic effect on mortality was that of an age-1 mutation, which lowered mortality more than fivefold at most later ages. In contrast, a spe-26 mutant had a tenfold lower mortality until approximately 2 weeks of age but ultimately achieved a higher mortality, whereas clk-1 mutants show slightly higher mortality than wild type during the fertile period, early in life, but ultimately level off at lower mortality. Each mutant thus has a distinctive profile of age-specific mortalities that could suggest the time of action of each gene.
Johnson
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Institute for Behavioral Genetics, University of Colorado, Boulder, CO 80309, USA. johnsont@colorado.edu
Wu
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Tedesco
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Dames
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Vaupel
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JW
D000375:Aging / Q000235:genetics*; D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics*; D046508:Culture Techniques; D005260:Female; D008136:Longevity / Q000235:genetics; D008297:Male; D023421:Models, Animal; D008962:Models, Theoretical; D009154:Mutation / Q000235:genetics*; D012680:Sensitivity and Specificity; D016019:Survival Analysis