Uncoupling lifespan and healthspan in <i>Caenorhabditis elegans</i> longevity mutants

Significance Genetic and environmental manipulations have been identified that result in lifespan extension. The underlying assumption that lifespan extension would also result in an increase in healthspan(definition) is seemingly valid but infrequently examined. Here, we examined multiple pathways that modulate lifespan to investigate the relationship between lifespan extension and health. We analyzed wild-type and four long-lived mutants in an unbiased cross-sectional study with multiple assays until animals reached 80% maximum lifespan. We show lifespan and healthspan can be separated and all of the long-lived mutants extend the period of frailty as a consequence. If applied to humans, this would likely lead to unsustainable healthcare costs and demonstrates the importance of examining healthspan as opposed to lifespan for future research.