PDF(Pubmed)
Abstract：
Lifespan varies within and across species, but the general principles of its control remain unclear. Here, we conducted multi-tissue RNA-seq analyses across 41 mammalian species, identifying longevity signatures and examining their relationship with transcriptomic biomarkers of aging and established lifespan-extending interventions. An integrative analysis uncovered shared longevity mechanisms within and across species, including downregulated Igf1 and upregulated mitochondrial translation genes, and unique features, such as distinct regulation of the innate immune response and cellular respiration. Signatures of long-lived species were positively correlated with age-related changes and enriched for evolutionarily ancient essential genes, involved in proteolysis and PI3K-Akt signaling. Conversely, lifespan-extending interventions counteracted aging patterns and affected younger, mutable genes enriched for energy metabolism. The identified biomarkers revealed longevity interventions, including KU0063794, which extended mouse lifespan and healthspan. Overall, this study uncovers universal and distinct strategies of lifespan regulation within and across species and provides tools for discovering longevity interventions.
摘要：
寿命在物种内部和物种之间变化，但其控制的一般原则仍不清楚。这里,我们对41种哺乳动物进行了多组织RNA-seq分析，确定长寿特征，并检查它们与衰老的转录组生物标志物和已建立的延长寿命的干预措施的关系。综合分析揭示了物种内部和物种之间共享的长寿机制，包括下调的Igf1和上调的线粒体翻译基因，和独特的功能，如先天免疫反应和细胞呼吸的不同调节。长寿物种的特征与年龄相关的变化呈正相关，并丰富了进化上古老的必需基因，参与蛋白水解和PI3K-Akt信号传导。相反，延长寿命的干预措施抵消了衰老模式，并影响了年轻人，可变基因丰富的能量代谢。确定的生物标志物揭示了长寿干预措施，包括KU0063794，延长了小鼠的寿命和健康。总的来说,这项研究揭示了物种内和物种间寿命调节的普遍和独特的策略，并为发现寿命干预措施提供了工具。
