As ageing manifests a systematic decline across tissues, inter-tissue signalling is crucial to animal ageing. In a recent study published in Nature Communications, the team led by Prof. SHEN Yidong and Prof. WU Ligang from the Centre for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology of the Chinese Academy of Sciences, and Prof. HAN Jingdong from Peking University reported an atlas of age-dependent miRNAomic changes in and across individual C. elegans tissues.
MicroRNAs (miRNAs) are a class of small RNAs that regulate gene expression by binding to the 3’-UTR of targeted mRNAs. Besides their intracellular roles, recent studies have identified miRNAs as intercellular communicators. The SHEN lab previously identified that miR-83 secreted from the intestine impairs autophagy in the body wall muscle during C. elegans ageing, highlighting the potential of miRNAs as inter-tissue ageing signals. Yet, a comprehensive view of miRNAs as ageing regulators within individual tissues and as inter-tissue messengers coordinating the ageing of various tissues remains missing.
In this study, the researchers first isolated five major worm somatic tissues and profiled their age-dependent miRNAomes. Meanwhile, they assessed miRNAs transcription using GFP reporters driven by miRNA promoters in both young and aged worms. The researchers also analyzed miRNAomes in the extracellular vesicles (EV) of worms at different ages. The three datasets show miRNAs in the distributed tissue, the source tissue, and the vehicle of inter-tissue transport during ageing, respectively.
By integrating the three datasets, the researchers were able to map the age-dependent miRNAomic changes in individual worm tissues and also discovered numerous inconsistencies between miRNA source and distribution, implying extensive inter-tissue miRNA trafficking. Guided by these findings, the researchers charted the miRNA signalling network across tissues and found this network also under the regulation of ageing.
These miRNA atlases in and across worm tissues during ageing suggest a wide variety of miRNA functions in ageing. Based on these predictions, the researchers discovered that miR-1 from muscle controls DAF-16/FOXO in the intestine, underscoring circulating miR-1 in insulin/IGF signalling across tissues. The miRNA maps presented in this study pave the way for future investigations into the role of other miRNAs in the ageing process.
Contact: Yidong.shen@sibcb.ac.cn
Reference: https://www.nature.com/articles/s41467-024-45249-4
Appendix：
