Evidence item

Here, using Drosophila as a model, we show that restricting protein intake during the larval stage (early-life protein restriction; ePR) promotes adult lifespan by reducing the levels of storage proteins. Using stable-isotope tracing, we show that dietary amino acids obtained in the larval stage are retained into early adulthood, and are incorporated into ribosomal proteins in particular. This is mediated by larval serum protein 2 (Lsp2), a major storage protein, the expression of which is durably downregulated by ePR in the early adult stage. Genetic silencing of Lsp2 phenocopies ePR, attenuating ribosomal-protein abundance and translational activity in early adulthood, and extending lifespan. Restricting specific amino acids that are especially enriched in these storage proteins, such as phenylalanine and tyrosine, is sufficient to decrease the levels of early-life Lsp2 and promote longevity.