Caloric restriction (CR) improves healthspan and lifespan of organisms ranging from yeast to mammals. Understanding the mechanisms involved will uncover future interventions for aging associated diseases. In budding yeast, Saccharomyces cerevisiae, CR is commonly defined by reduced glucose in the growth medium, which extends both replicative and chronological lifespan (CLS). We found that conditioned media collected from stationary phase CR cultures extended CLS when supplemented into non-restricted (NR) cultures, suggesting a potential cell non-autonomous mechanism of CR-induced lifespan regulation. Chromatography and untargeted metabolomics of the conditioned media, as well as transcriptional responses associated with the longevity effect, pointed to specific amino acids enriched in the CR conditioned media (CRCM) as functional molecules, with L-serine being a particularly strong candidate. Indeed, supplementing L-serine into NR cultures extended CLS through a mechanism dependent on the one-carbon metabolism pathway, thus implicating this conserved and central metabolic hub in lifespan regulation.

中文翻译：

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热量限制和一碳代谢调节酵母时间老化的细胞非自主机制

热量限制 (CR) 可改善从酵母到哺乳动物等生物体的健康状况和寿命。了解所涉及的机制将揭示未来对衰老相关疾病的干预措施。在芽殖酵母（酿酒酵母）中，CR 通常是指生长培养基中葡萄糖含量降低，从而延长了复制寿命和时间寿命 (CLS)。我们发现，从稳定期 CR 培养物收集的条件培养基在补充到非限制性 (NR) 培养物中时可延长 CLS，这表明 CR 诱导的寿命调节存在潜在的细胞非自主机制。条件培养基的色谱分析和非靶向代谢组学，以及与长寿效应相关的转录反应，表明 CR 条件培养基 (CRCM) 中富含的特定氨基酸是功能分子，L-丝氨酸是特别有力的候选者。事实上，在 NR 培养物中补充 L-丝氨酸通过依赖于一碳代谢途径的机制延长了 CLS，从而暗示了这种保守的中央代谢中心在寿命调节中的作用。