A long-standing paradigm holds that stochastic aberrations of transcriptional regulation play a key role in the process of aging. While transcriptional dysregulation is observed in the majority of cell types in the form of increased cell-to-cell variability, its generality to all cell types remains doubted. Here, a novel approach is proposed for analyzing transcriptional regulation in single-cell RNA sequencing (scRNA-seq) data by focusing on the global coordination between the genes rather than the variability of individual genes or correlations between pairs of genes. Consistently, across different organisms and cell types, a decrease in the gene-to-gene transcriptional coordination is found in aging cells. In addition, loss of gene-to-gene transcriptional coordination is associated with a high mutational load of a specific, age-related signature and with radiation-induced DNA damage. These observations suggest a general, potentially universal, stochastic attribute of transcriptional dysregulation in aging.

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