Inter-tissue convergence of gene expression and loss of cellular identity during ageing

Gene expression tends to reverse its developmental trajectory direction in ageing, a phenomenon previously linked to cellular identity loss. Our analysis of cortex, lung, liver and muscle transcriptomes of 16 mice, covering development and ageing intervals, revealed widespread but tissue-specific ageing-associated expression reversals. Cumulatively, these reversals create a unique phenomenon: mammalian tissue transcriptomes diverge from each other during postnatal development, but during ageing, they tend to converge towards similar expression levels, a process we term divergence-convergence, or DiCo. We confirmed the DiCo pattern using data from independent mouse and human datasets. Further, using publicly available single-cell transcriptome data, we showed that DiCo could be driven both by alterations in tissue cell type composition and also by cell-autonomous expression changes within particular cell types.