Over the past decade, biogerontologists have demonstrated that several types of mutations can dramatically extend the lifespan of experimental model organisms. Not only do the mutants live longer, they appear to age more slowly, maintaining vigor and a youthful appearance long after their wildtype counterparts have started to die.
Why, then, are these artificially created mutant alleles not the wildtype? In other words, if lacking a particular gene makes an animal longer-lived and more vigorous, why do all wildtype members of the species have the gene in the first place?
Chen et al. address this question in the grandmother (“grand-hermaphrodite”?) of aging models, the nematode worm C. elegans. They quantitatively measured fitness in wildtype worms and two mutants that extend lifespan in different ways — daf-2, an IGF-1 receptor, and clk-1, an enzyme involved in ubiquinone biosynthesis — and found that both longer-lived mutants are significantly less fit, in an evolutionary sense, than the wildtype.
A Demographic Analysis of the Fitness Cost of Extended Longevity in Caenorhabditis elegans
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 (lambda = 2.74) and daf-2 (lambda = 3.78) at a disadvantage relative to N2 (lambda = 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.
Note that the fitness decrease isn’t caused by the overall decrease in lifetime fertility, but rather the delay in early-life reproduction. This makes sense, in the relentless logic of exponential growth: The earlier one reproduces, the earlier one’s progeny are available to do reproduction of their own. As a thought experiment, consider what would happen if one variant of a species reproduces once on day 5 of life but dies on day 6, whereas another variant reproduces on days 6 and 12 and dies on day 13. It’s pretty clear that eventually the short-lived early-reproducer would out-compete the long-lived late-reproducer, even though (in this imaginary example) the total lifetime fertility of the longer-lived variant is actually higher.
This is the idea of “antagonistic pleiotropy” referred to in the last sentence of the abstract: Traits that shorten the overall lifespan can be positively selected for if they increase the reproductive success (fitness) of the organism. Examples of this phenomenon in humans are the prostate and breast, in which high proliferative capacity is good for fitness (reproduction and child-rearing, respectively), but pose a cancer risk in the post-reproductive stage of life.