跨物种和物种内部的不同寿命机制及其与衰老的关联
Alexander Tyshkovskiy1, Siming Ma2, Anastasia V Shindyapina2
1Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA; Belozersky Institute of Physico-Chemical Biology, Moscow State University, Moscow 119234, Russia.
Cell
|June 3, 2023
概括
科学家发现了控制41种哺乳动物寿命的普遍和独特的遗传策略. 关键的发现包括与长寿和衰老相关的特定基因表达模式,为寿命延长研究提供了新的途径.
科学领域:
- 基因组学
- 比较生物学
- 老龄化研究
背景情况:
- 生命周期在物种之间有很大差异,但基本的遗传和分子控制机制在很大程度上是未知的.
- 了解这些原则对于解决与年龄相关的疾病和促进健康老龄化至关重要.
研究的目的:
- 识别与哺乳动物长寿相关的保存和特定物种的遗传特征.
- 研究长寿特征,衰老的转录基因生物标志物和延长寿命的干预措施之间的关系.
- 发现规范生命周期的普遍和独特策略.
主要方法:
- 在41种哺乳动物中进行了多组织RNA测序 (RNA-seq).
- 使用整合性分析识别长寿特征,并将其与衰老生物标志物和干预效应进行比较.
- 分析了转录组数据,以发现基因表达模式与寿命之间的相关性.
主要成果:
- 跨物种共享的长寿机制包括胰岛素样生长因子1 (Igf1) 的下调和线粒体转化基因的上调.
- 不同的物种特异性机制涉及天生的免疫和细胞呼吸的差异调节.
- 长寿物种的长寿特征与与年龄相关的变化相关,并涉及蛋白质分解和PI3K-Akt信号的古老基因.
- 通过影响参与能量代谢的年轻基因,
- 确定了一种特殊的干预措施,KU0063794,以延长小鼠的寿命和健康期.
结论:
- 这项研究揭示了哺乳动物生命周期调节的普遍和独特的分子策略.
- 已识别的生物标志物和遗传特征为发现新型寿命干预提供了宝贵的工具.
- 这些发现有助于更深入地了解整个哺乳动物类的衰老和寿命的遗传基础.
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