Intermediate leucine catabolism is associated with longevity and sustained reproduction in grasshoppers

Dietary isoleucine restriction improves metabolic health and lifespan in animal models. It is hypothesized that shifts in branched-chain amino acid catabolism drive longevity. We investigated dietary isoleucine restriction on organismal branched-chain amino acid catabolism and its association with longevity and reproduction. In two main experiments, adult female Lubber grasshoppers were assigned to a high-quality diet (Bal ile) or diets with two levels of isoleucine content (moderate isoleucine restriction [Mod ile-R] or severe isoleucine restriction [Sev ile-R]). In Experiment 2, we used a low-energy (Low Lett) group as a positive control for catabolism. In Experiment 3, we used an ad libitum lettuce (Ad Lib Lett) control to show the reproduction-longevity trade-off. Nutrient-specific, organismal catabolism was measured by tracking ¹³C in an ingested amino acid through catabolism to breath CO₂. The Bal ile, Mod ile-R, and Sev ile-R diets extended lifespan and increased leucine catabolism relative to the Ad Lib Lett group. The Sev ile-R and Low Lett groups showed the highest leucine catabolism but greatly reduced reproduction. The Bal ile group showed intermediate leucine catabolism while sustaining reproduction. The Mod ile-R group had intermediate leucine catabolism but delayed reproduction. There was no compensatory feeding on low isoleucine diets. Valine catabolism did not show statistical significance but tended to show similar trends to leucine catabolism. Weak leucine catabolism is linked to a short lifespan, while excessive leucine catabolism is linked to impaired reproduction. Intermediate levels of leucine catabolism were associated with longevity and sustained reproduction.