美国哈佛医学院Vadim N. Gladyshev团队近期的研究鉴定到与寿命延长有关的基因表达特征并开发了相关应用。相关论文于2019年9月3日发表在《细胞—代谢》杂志上。

研究人员对进行了8种长寿干预的小鼠进行了RNA测序（RNA-seq）分析。研究人员发现女性化效应与生长激素调节和性别相关差异的减少相关。将这一分析扩展到17项公共数据干预，研究人员表观察到许多干预措施诱导了类似的基因表达变化。研究人员通过干预措施确定了与寿命延长相关的肝基因特征，包括氧化磷酸化和药物代谢的上调，并发现了受干扰的途径能够在组织间共享。研究人员进一步应用发现的长寿特征来识别新的延长寿命的选项，例如慢性缺氧、KU-0063794和抗坏血酸棕榈酸酯。最后，研究人员开发了GENtervention，这是一个可视化基因表达变化和长寿之间关联的应用程序。总体而言，这项研究描述了小鼠寿命延长的普遍和特定转录组程序，并提供了发现新干预措施的工具。

研究人员表示，几种能够增加哺乳动物寿命的药理、饮食和遗传干预措施已经知道，但延长寿命的普遍原则仍不清楚。

附：英文原文

Title: Identification and Application of Gene Expression Signatures Associated with Lifespan Extension

Author: Richard A. Miller, Vadim N. Gladyshev,et al

Issue&Volume: Volume 30 Issue 3

Abstract: Several pharmacological, dietary, and genetic interventions that increase mammalian lifespan are known, but general principles of lifespan extension remain unclear. Here, we performed RNA sequencing (RNA-seq) analyses of mice subjected to 8 longevity interventions. We discovered a feminizing effect associated with growth hormone regulation and diminution of sex-related differences. Expanding this analysis to 17 interventions with public data, we observed that many interventions induced similar gene expression changes. We identified hepatic gene signatures associated with lifespan extension across interventions, including upregulation of oxidative phosphorylation and drug metabolism, and showed that perturbed pathways may be shared across tissues. We further applied the discovered longevity signatures to identify new lifespan-extending candidates, such as chronic hypoxia, KU-0063794, and ascorbyl-palmitate. Finally, we developed GENtervention, an app that visualizes associations between gene expression changes and longevity. Overall, this study describes general and specific transcriptomic programs of lifespan extension in mice and provides tools to discover new interventions.

DOI: https://doi.org/10.1016/j.cmet.2019.06.018

Source: https://www.cell.com/cell-metabolism/fulltext/S1550-4131(19)30372-9#