Abstract
Signaling factors, both external from an organism's environment and produced internally by its tissues, regulate the rate of aging. Loss of beneficial signals drives systemic aging, and conversely, restoring these youth-associated signals can rejuvenate an aging individual, as demonstrated by heterochronic parabiosis. Finding factors that promote organismal health and longevity therefore holds great therapeutic promise to slow aging and age-associated disease. Here, we report that exposure to the lysed remains of other worms extends C. elegans lifespan. This lifespan extension is not mediated by ascaroside pheromones and is not induced by bacterial cell lysate, suggesting that this effect is not merely produced by nutritional supplementation of cellular contents. We found that a period of discrete exposure at any point across the lifespan is sufficient to induce longevity. However, distinct pathways were activated in young and aged recipients; we found that lysate factors act through insulin/insulin-like growth factor/FOXO signaling (IIS) in young worms, while IIS-independent pathways extend lifespan in older worms. Using fluorescent gene reporter lines, we provide evidence that intestinal IIS is not activated in young worms, suggesting that lysate signals promote longevity via non-intestinal tissues. Our work identifies a novel longevity paradigm in which the remains of deceased C. elegans extend the lifespans of living conspecifics through multiple parallel pathways.