Aging increases cell-to-cell transcriptional variability upon immune stimulation
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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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1095-9203
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Cancer Research UK (C14303/A17197)
Wellcome Trust (107609/Z/15/Z)
Cancer Research UK (unknown)
Cancer Research UK (20412)
Wellcome Trust (202878/Z/16/Z)
Cancer Research UK (17043)
Cancer Research UK (22231)
Cancer Research UK (22257)