德国萨尔大学Andreas Keller和美国斯坦福大学Tony Wyss-Coray团队共同合作，近期取得重要工作进展。他们研究发现了小鼠组织衰老和异时共生过程中非编码RNA表达变化的特征。相关研究成果2023年4月27日在线发表于《自然—生物技术》杂志上。

据介绍，生物体和细胞衰老的分子机制尚不完全清楚。研究人员生成了一个非编码RNA（ncRNA）在衰老（从1个月到27个月的10个时间点的16个器官）和恢复活力小鼠中的全身表达图谱。

研究人员发现，除了八种广泛失调的微小RNA（miRNA）外，分子衰老轨迹在很大程度上是组织特异性的。它们的个体丰度反映了它们在循环血浆和细胞外小泡（EV）中的存在，而组织特异性ncRNA的存在较少。对于miR-29c-3p，研究人员在实体器官、血浆和EV中观察到与衰老的最大相关性。在通过异时共生恢复活力的小鼠中，miR-29c-3p是最显著的miRNA，能恢复到年轻肝脏中发现的类似水平。miR-29c-3p靶向已知与衰老有关的细胞外基质和分泌途径。

总之，研究人员提供了ncRNA在衰老和再生过程中的全生物体表达图谱，并鉴定了一组广泛失调的miRNA，它们可能通过血浆和EV作为衰老的系统性调节因子。

附：英文原文

Title: Characterizing expression changes in noncoding RNAs during aging and heterochronic parabiosis across mouse tissues

Author: Wagner, Viktoria, Kern, Fabian, Hahn, Oliver, Schaum, Nicholas, Ludwig, Nicole, Fehlmann, Tobias, Engel, Annika, Henn, Dominic, Rishik, Shusruto, Isakova, Alina, Tan, Michelle, Sit, Rene, Neff, Norma, Hart, Martin, Meese, Eckart, Quake, Steve, Wyss-Coray, Tony, Keller, Andreas

Issue&Volume: 2023-04-27

Abstract: Molecular mechanisms of organismal and cell aging remain incompletely understood. We, therefore, generated a body-wide map of noncoding RNA (ncRNA) expression in aging (16 organs at ten timepoints from 1 to 27 months) and rejuvenated mice. We found molecular aging trajectories are largely tissue-specific except for eight broadly deregulated microRNAs (miRNAs). Their individual abundance mirrors their presence in circulating plasma and extracellular vesicles (EVs) whereas tissue-specific ncRNAs were less present. For miR-29c-3p, we observe the largest correlation with aging in solid organs, plasma and EVs. In mice rejuvenated by heterochronic parabiosis, miR-29c-3p was the most prominent miRNA restored to similar levels found in young liver. miR-29c-3p targets the extracellular matrix and secretion pathways, known to be implicated in aging. We provide a map of organism-wide expression of ncRNAs with aging and rejuvenation and identify a set of broadly deregulated miRNAs, which may function as systemic regulators of aging via plasma and EVs.

DOI: 10.1038/s41587-023-01751-6

Source: https://www.nature.com/articles/s41587-023-01751-6