Intra- and inter-organ communications in aging and cancer: Local and global spatial perspectives

Interactions among neighbouring cells are fundamental to tissue function and can be specifically mapped using single-cell and spatial transcriptomics data. Overall, cell-cell interactions (CCIs) are essential for proper tissue function, including cell development, maintenance of tissue homeostasis, and immune responses during disease. Cells also communicate between organs by releasing signalling molecules into the circulatory system. We examined aging and cancer progression, the two important biological processes where alterations in CCIs remodel the tissue microenvironments that drive cellular and tissue dysfunction. Identifying these dysregulated interactions can uncover potential therapeutic strategies to prevent or treat disease by targeting specific ligand-receptor interactions. Interestingly, in aging and cancer metastasis, ligands originating from one organ can influence the aging processes of distant organs, while local interactions within the tumour microenvironment are critical for not only cancer dynamics at the primary site but also for driving its progression to secondary organs. This review highlights key ligand-receptor interactions in aging and cancer metastasis and examines intra- and inter-organ communication inference tools in this emerging field.