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An adipose mTORC1 effector mediates antagonism between ribosomal protein translation and lifespan

ABSTRACT: mTOR complex 1 (mTORC1) senses nutrient availability and instructs accordingly fundamental metabolic processes including protein synthesis to maintain physiological homeostasis. Reducing mTORC1 activity by caloric restriction, rapamycin treatment, or genetic manipulation, extends lifespan in diverse model organisms, yet how to rationally design strategies for mTORC1 intervention without compromising normal organismal physiology remains to be explored. Using Drosophila model, we report here the characterization of an adipokine, Lsp2, as a nutrient-dependent regulator of mTORC1 signaling outputs. This adipokine is strongly induced by protein diets and controlled by the insulin-mTORC1 signaling axis, while reminiscent of their effects in ageing, Lsp2 negatively regulates lifespan. Loss of Lsp2 robustly extends lifespan and health span notably on protein-rich diets by specifically and globally reducing 4E-BP-dependent translation of ribosomal proteins, a mechanism distinct from that of rapamycin. Our data thus support a novel concept that an inducible mechanism that enhances the translation of proteins making up the translation machinery, is encoded beyond the mTORC1-4E-BP core signaling module, and targeting such auxiliary translation-enhancing mechanism provides health benefits in the context of ageing and overnutrition.

ORGANISM(S): Drosophila melanogaster

PROVIDER: GSE295794 | GEO | 2026/07/16

REPOSITORIES: GEO

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An adipose mTORC1 effector links nutrient-induced ribosomal protein translation to lifespan in Drosophila

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| PXD062930 | JPOST Repository