A Demographic Analysis of the Fitness Cost of Extended Longevity in Caenorhabditis elegans

Abstract

We monitored survival and reproduction of 1000 individuals of Caenorhabditis elegans wild type (N2) and 800 individuals of clk-1 and daf-2, and used biodemographic analysis to address fitness as the integrative consequence of the entire age-specific schedules of survival and reproduction. Relative to N2, the mutants clk-1 and daf-2 extended average life span by 27% and 111%, respectively, but reduced net reproductive rate by 44% and 18%. The net result of differences in survival and fertility was a significant differential in fitness, with both clk-1 (k ¼ 2.74) and daf-2 (k ¼ 3.78) at a disadvantage relative to N2 (k ¼ 3.85). Demographic life table response experiment (LTRE) analysis revealed that the fitness differentials were due to negative effects in mutants on reproduction in the first 6-7 days of life. Fitness costs in clk-1 and daf-2 of C. elegans are consistent with the theory of antagonistic pleiotropy for the evolution of senescence.

Variance in animal longevity: contributions of heterogeneity and stochasticity

“…To clarify the analyses and as an example of the procedure, we present here the detailed results for a cohort of 800 individuals of the CLK-1 strain of the nematode C. elegans from an experiment described in Chen et al (2007). Fitting a single Weibull function to the age-at-death data of this strain yields an estimate of = 20.7 and k = 1.9.…”

“…Mortality data on C. elegans was obtained from a experiment by Chen et al (2007). In this experiment, the longevity of a standard wild-type strain (N2) and two long-lived mutant strains (CLK-1 and DAF-2) were reported.…”

Mutation Patterns Due to Converging Mitochondrial Replication and Transcription Increase Lifespan, and Cause Growth Rate-Longevity Tradeoffs

“…For lifespan, convergence decreases cumulation of mutations and in general, increases mutational robustness; for developmental rates, they are the direct result of decreased replication and transcription rates because of increased collision frequencies between replication and transcription forks. It is notable that this rationale yields a molecular mechanism for the well known negative association between metabolic rates and longevities, as described in Insects (Antler flies, Bonduriansky & Brassil, 2005;Drosophila, Marden et al, 2003;Novoseltsev et al, 2005;Mockett & Sohal, 2006), nematodes (Jenkins et al, 2004;Chen et al, 2007;Lee et al, 2006;Hughes et al, 2007) and mice (Cargill et al, 2003;and others, Bonsall, 2006). Some ecological data explaining the tradeoffs exist (Bonduriansky & Brassil, 2005), and results suggest the tradeoff is due to dietary metabolism (Partridge et al, 2005a,b;Speakman, 2005a,b;Kaeberlein et al 2006;Ruggiero & Ferrucci, 2006;Szewczyk et al, 2006;Wolkow & Iser, 2006).…”

Progress & Prospects: Gene therapy in aging

“…There is some evidence that laboratory-protected longevity mutants in C. elegans have reduced Darwinian fitness when competing with the wild-type worms under nutritionally challenging conditions. 26,27 Similarly, klotho-induced insulin resistance and the paradox of the insulin/IGF-1 signaling pathways in longevity extension seriously question the practicality of such gene manipulations in humans. 26,28 Human life span is associated with polymorphisms in genes…”