Aging increases cell-to-cell transcriptional variability upon immune stimulation
Celia Pilar Martinez-Jimenez1,2, Nils Eling1,3, Hung-Chang Chen1
1University of Cambridge, Cancer Research UK Cambridge Institute, Robinson Way, Cambridge, CB2 0RE, UK.
Science (New York, N.Y.)
|April 1, 2017
Summary
Aging impairs the immune system by disrupting gene expression in CD4+ T cells. This study reveals increased cell-to-cell variability in gene activity as a key aging hallmark in mammals.
Area of Science:
- Immunology
- Molecular Biology
- Gerontology
Background:
- Aging leads to a decline in physiological functions, but the underlying molecular mechanisms are not fully understood.
- Cellular functions degrade with age, impacting overall health and immune response.
- The molecular basis of aging-related functional decline requires further investigation.
Purpose of the Study:
- To investigate the impact of aging on transcriptional dynamics in CD4+ T cells.
- To compare aging effects on gene expression heterogeneity in two species.
- To identify conserved molecular changes associated with aging in immune cells.
Main Methods:
- Single-cell RNA sequencing was employed to analyze gene expression.
- Naïve and effector memory CD4+ T cells from young and old mice were studied.
- Cells were analyzed in both unstimulated and stimulated states.
Main Results:
- In young mice, immune activation led to coordinated gene expression and reduced cell-to-cell variability.
- Aging disrupted the activation of core immune gene programs.
- Increased gene expression heterogeneity was observed in aged CD4+ T cells across both species.
Conclusions:
- Aging perturbs the tightly regulated gene expression programs crucial for immune cell function.
- Increased cell-to-cell transcriptional variability is a significant molecular feature of aging.
- This variability may be a conserved hallmark of aging across mammalian tissues.
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