创作:szx 审核:szx 2019年08月10日
  • 使用能量限制、17-α-雌二醇、雷帕霉素、Pit1敲除等8种不同的长寿干预措施处理小鼠,并进行RNA测序分析;
  • 发现长寿干预后,小鼠发生与生长激素调节相关的雌性化效应,且性别相关差异减小;
  • 除雷帕霉素外的长寿干预措施使小鼠表现出类似的转录应答;
  • 鉴定出与寿命延长相关的肝脏基因表达特征,包括氧化磷酸化、药物代谢相关基因的上调;
  • 利用鉴定出的基因表达特征,发现了一些新的潜在长寿干预措施,包括慢性低氧、抗坏血酸棕榈酸酯等。
Cell Metabolism上发表的一项最新研究,在小鼠中鉴定出了与特定的长寿相关基因表达模式,并基于该模式发现了一些新的潜在长寿干预措施。
Cell Metabolism [IF:22.415]

Identification and Application of Gene Expression Signatures Associated with Lifespan Extension



2019-07-25, Resource

Abstract & Authors:展开

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.

First Authors:
Alexander Tyshkovskiy

Correspondence Authors:
Vadim N Gladyshev

All Authors:
Alexander Tyshkovskiy,Perinur Bozaykut,Anastasia A Borodinova,Maxim V Gerashchenko,Gene P Ables,Michael Garratt,Philipp Khaitovich,Clary B Clish,Richard A Miller,Vadim N Gladyshev