title: What can long-lived mutants tell us about mechanisms causing aging and lifespan variation in natural environments?
abstract: Long-lived mutants of model organisms have brought remarkable progress in our understanding of aging mechanisms. However, long-lived mutants are usually maintained in optimal standardized laboratory environments (SLEs), and it is not obvious to what extent insights from long-lived mutants in SLEs can be generalized to more natural environments. To address this question, we reviewed experiments that compared the fitness and lifespan advantage of long-lived mutants relative to wild type controls in SLEs and more challenging environments in various model organisms such as yeast Saccharomyces cerevisiae, the nematode worm Caenorhabditis elegans, the fruitfly Drosophila melanogaster and the mouse Mus musculus. In competition experiments over multiple generations, the long-lived mutants had a lower fitness relative to wild type controls, and this disadvantage was the clearest when the environment included natural challenges such as limited food (N=6 studies). It is well known that most long-lived mutants have impaired reproduction, which provides one reason for the fitness disadvantage. However, based on 12 experiments, we found that the lifespan advantage of long-lived mutants is diminished in more challenging environments, often to the extent that the wild type controls outlive the long-lived mutants. Thus, it appears that information on aging mechanisms obtained from long-lived mutants in SLEs may be specific to such environments, because those same mechanisms do not extend lifespan in more natural environments. This suggests that different mechanisms cause variation in aging and lifespan in SLEs compared to natural populations.
authors.affiliation: Groningen Institute for Evolutionary Life Sciences, University of Groningen, 9747 AG Groningen, the Netherlands. Electronic address: michbriga@gmail.com.
authors.forename: Michael
authors.initials: M
authors.lastname: Briga
authors.affiliation: Groningen Institute for Evolutionary Life Sciences, University of Groningen, 9747 AG Groningen, the Netherlands. Electronic address: s.verhulst@rug.nl.
authors.forename: Simon
authors.initials: S
authors.lastname: Verhulst
mesh_terms: D000375:Aging / Q000235:genetics*; D000818:Animals; D000830:Animals, Laboratory / Q000502:physiology; D000835:Animals, Wild / Q000502:physiology; D004777:Environment; D008136:Longevity / Q000235:genetics; D009154:Mutation / Q000502:physiology*
keywords: Aging; Lifespan; Model organisms; Mutants; Senescence