Animal lifespan is regulated by conserved metabolic signalling pathways and specific transcription factors, but whether these pathways affect common downstream mechanisms remains largely elusive. Here we show that NCL-1/TRIM2/Brat tumour suppressor extends lifespan and limits nucleolar size in the major C. elegans longevity pathways, as part of a convergent mechanism focused on the nucleolus. Long-lived animals representing distinct longevity pathways exhibit small nucleoli, and decreased expression of rRNA, ribosomal proteins, and the nucleolar protein fibrillarin, dependent on NCL-1. Knockdown of fibrillarin also reduces nucleolar size and extends lifespan. Among wildtype C. elegans, individual nucleolar size varies, but is highly predictive for longevity. Long-lived dietary restricted fruit flies and insulin-like-peptide mutants exhibit small nucleoli and fibrillarin expression, as do long-lived dietary restricted and IRS1 knockout mice. Furthermore, human muscle biopsies from individuals who underwent modest dietary restriction coupled with exercise also display small nucleoli. We suggest that small nucleoli are a cellular hallmark of longevity and metabolic health conserved across taxa.

中文翻译：

---

小核仁是长寿的细胞标志。

动物的寿命受保守的代谢信号传导途径和特定转录因子的调控，但是这些途径是否影响共同的下游机制仍然很难确定。在这里，我们显示NCL-1 / TRIM2 / Brat肿瘤抑制因子可延长寿命并限制主要秀丽隐杆线虫寿命途径中的核仁大小，这是聚焦于核仁的收敛机制的一部分。代表不同寿命途径的长寿动物表现出小的核仁，依赖NCL-1的rRNA，核糖体蛋白和核仁蛋白原纤维蛋白的表达降低。击倒原纤维蛋白还可以减少核仁大小并延长寿命。在野生型秀丽隐杆线虫中，单个核仁的大小各不相同，但对寿命的预测很高。长期饮食限制的果蝇和胰岛素样肽突变体表现出小的核仁和原纤维蛋白表达，长期饮食限制的和IRS1基因敲除小鼠也是如此。此外，经过适度饮食限制和运动的个体的人体肌肉活检也显示出小的核仁。我们建议，小核仁是整个类群中长寿和代谢健康的细胞标志。