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Lsp2将生命早期饮食与成年期翻译及寿命联系起来(果蝇)

Lsp2 links early-life diet to adult translation and lifespan in Drosophila

Nature · 2026 年 9 月 23 日 · Hina Kosakamoto, Rina Okada, Clive S Barker 等 8 人

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果蝇幼期蛋白限制通过降低储存蛋白Lsp2延长成年寿命。

近百年前就有人提出生命早期限制饮食可延长寿命,但机制不清。本研究以果蝇为模型,发现幼虫期限制蛋白摄入能延长成年寿命,其机制是降低储存蛋白水平。稳定同位素示踪显示,幼虫期摄入的氨基酸会保留到成年早期并优先掺入核糖体蛋白,这一过程由储存蛋白Lsp2介导。沉默Lsp2可模拟早期蛋白限制、降低成年早期翻译活性并延长寿命。研究揭示了一种“营养记忆”机制,将幼年营养状态与成年翻译能力和寿命联系起来。

为什么推荐给您:在果蝇中揭示早期营养经Lsp2影响成年翻译与寿命的新机制,具基础科学突破意义。

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摘要Abstract

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Nearly a century ago, restricting diet during early-life periods was suggested to extend lifespan in rats and in Daphnia1,2. The effect of juvenile diet on adult physiology and lifespan has subsequently been described in other model organisms, including fruit flies3-5 and mice6-8; however, its mechanism remains poorly understood. 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. These findings identify Lsp2 as a molecular carrier of nutritional history across developmental transitions, linking juvenile nutritional status to adult translational capacity and lifespan. Our study uncovers a previously unrecognized mechanism of nutritional memory that links early-life diet to lifelong organismal health.

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