How a Mutation that Slows Aging Can Also Disproportionately Extend End-of-Life Decrepitude

Publication date: 18 April 2017
Source:Cell Reports, Volume 19, Issue 3
Author(s): Katie Podshivalova, Rex A. Kerr, Cynthia Kenyon
The goal of aging research is to extend healthy, active life. For decades, C. elegans daf-2 insulin/insulin-like growth factor 1 (IGF-1) receptor mutants have served as a model for extended lifespan and youthfulness. However, a recent report suggested that their longevity is associated with an undesirable phenotype: a disproportionately long period of decrepitude at the end of life. In the human population, such an outcome would be a burden to society, bringing into question the relevance of daf-2 mutants as a model for life extension. However, here we report that, following an extended period of movement, daf-2 mutants survive longer in a decrepit state because of a beneficial trait: they are resistant to colonization of the digestive tract by dietary bacteria, a condition that leads to premature death in the wild-type and prevents their manifestation of decrepitude. If bacterial colonization is prevented, then daf-2 mutants lead both chronologically and proportionately healthier lives relative to the wild-type.

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Teaser

Podshivalova et al. show that long-lived C. elegans insulin/IGF-1 receptor mutants remain active longer but then resist bacterially induced mortality, allowing them to survive into a state of end-of-life decrepitude. Thus, changes that slow aging and also prevent an age-associated catastrophe can extend both the youthful and infirm periods of life.


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