Glucose enrichment accelerates C. elegans reproductive aging via non-autonomous DAF-2/insulin-like receptor signaling...

Reproductive systems are highly sensitive to diet, yet the long-term reproductive consequences of overnutrition are poorly defined. Glucose supplementation shortens Caenorhabditis elegans lifespan, and here we find that it also hastens age-related reproductive decline, evidenced by a greater oocyte deterioration and lower fertility with age. 20-mM glucose enrichment still shortens the lifespan of daf-2(e1370) mutants with reduced insulin-like signaling, but unexpectedly, we do not detect detrimental impacts on their reproductive aging phenotypes. Using auxin-induced tissue-selective degradation, we show that DAF-2/insulin-like receptor signaling in C. elegans intestine and body wall musculature is required for glucose enrichment to impair reproductive function of aged worms, and DAF-2 degradation in either tissue protects against glucose-induced reproductive aging. We also observe that disrupting lipid homeostasis via RNAi against the lipl-4 lipase can impair daf-2(e1370) reproductive function under glucose enrichment. Therefore, insulin-like signaling in metabolically active somatic tissues could represent a key link between overnutrition and reproductive aging.