An Adipose mTORC1 Effector Links Nutrient-induced Ribosomal Protein Translation to Lifespan in Drosophila

Mechanistic target of rapamycin complex 1 (mTORC1) senses nutrient availability to orchestrate metabolic processes critical for physiological homeostasis and organismal ageing ¹ . While mTORC1 preferentially regulates the translation of 5′-terminal oligopyrimidine (TOP) motif-containing mRNAs that predominantly encode ribosomal proteins (RPs) via the translational repressor 4E-BP ² , this mTORC1 function is resistant to rapamycin inhibition ³ . TOP mRNAs are exceptionally abundant, thus imposing a major translational burden on cells; yet how their translation is physiologically tuned and linked to longevity remain unexplored. Here we identify Lsp2, originally known as a storage protein ⁴ , as an adipose effector of mTORC1 that modulates lifespan in Drosophila . Lsp2 is induced by essential amino acids (EAAs) via mTORC1. Genetic ablation of Lsp2 to blunt organismal response to protein diets drives robust lifespan extension without compromising key life-history traits such as reproduction. Translatomic profiling reveals that loss of Lsp2 selectively reduces global TOP mRNA translation in a 4E-BP-dependent manner, thereby extending lifespan via a mechanism distinct from rapamycin inhibition that fails to reduce 4E-BP phosphorylation in vivo . Finally, Lsp2 adipokine promotes 4E-BP phosphorylation and acts systemically across tissues to shape the lifespan responses to dietary protein. Collectively, our findings establish Lsp2 as a novel translational regulator of TOP genes that mechanistically couples physiological ribosomal protein synthesis with organismal longevity.