TRL-1 undergoes phase separation to regulate the reproduction and longevity tradeoff

The antagonistic pleiotropy theory of aging proposes that genes enhancing fitness in early life limit lifespan, but the molecular evidence remains underexplored. By profiling translatome changes in Caenorhabditis elegans during starvation recovery, we demonstrate that an open reading frame (ORF) trl-1 'hidden' within an annotated pseudogene significantly translates upon refeeding. trl-1 mutant animals increase brood sizes but shorten lifespan and specifically impair the germline deficiency-induced longevity. The loss of trl-1 abnormally upregulates the translation of vitellogenin that produces copious yolk to provision eggs, whereas vitellogenin overexpression is known to reduce lifespan. We show that TRL-1 protein undergoes liquid-liquid phase separation, through which TRL-1 granules recruit vitellogenin mRNA and inhibit its translation. These results indicate that trl-1 functions as an antagonistic pleiotropic gene to regulate the reproduction-longevity tradeoff by optimizing nutrient production for the next generation. Overall design: Ribo-Seq and RNA-Seq of starved six days C. elegans larvae refed with bacterial food for 0, 10, 30, and 60 minutes (min) in wide-type(N2) animals , trl-1(cas1077) animals and trl-1(cas1078) animals. A reference sample was collected from the same culture condition from the non-starved (NS) animals, each strain was analyzed in biological duplicate.