Aging increases cell-to-cell transcriptional variability upon immune stimulation

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Science  31 Mar 2017:
Vol. 355, Issue 6332, pp. 1433-1436
DOI: 10.1126/science.aah4115

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Aging and variability among immune cells

How and why the immune system becomes less effective with age are not well understood. Martinez-Jimenez et al. performed single-cell sequencing of CD4+ T cells in old and young mice of two species. In young mice, the gene expression program of early immune activation was tightly regulated and conserved between species. However, as mice aged, the expression of genes involved in pathways responding to immune cell stimulation was not as robust and exhibited increased cell-to-cell variability.

Science, this issue p. 1433


Aging is characterized by progressive loss of physiological and cellular functions, but the molecular basis of this decline remains unclear. We explored how aging affects transcriptional dynamics using single-cell RNA sequencing of unstimulated and stimulated naïve and effector memory CD4+ T cells from young and old mice from two divergent species. In young animals, immunological activation drives a conserved transcriptomic switch, resulting in tightly controlled gene expression characterized by a strong up-regulation of a core activation program, coupled with a decrease in cell-to-cell variability. Aging perturbed the activation of this core program and increased expression heterogeneity across populations of cells in both species. These discoveries suggest that increased cell-to-cell transcriptional variability will be a hallmark feature of aging across most, if not all, mammalian tissues.

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