Sexual-dimorphism in human immune system aging

Eladio J. Márquez, Cheng-han Chung, Radu Marches, Robert J. Rossi, Djamel Nehar-Belaid, Alper Eroglu, David J. Mellert, George A. Kuchel, Jacques Banchereau and Duygu Ucar ()
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Eladio J. Márquez: The Jackson Laboratory for Genomic Medicine
Cheng-han Chung: The Jackson Laboratory for Genomic Medicine
Radu Marches: The Jackson Laboratory for Genomic Medicine
Robert J. Rossi: The Jackson Laboratory for Genomic Medicine
Djamel Nehar-Belaid: The Jackson Laboratory for Genomic Medicine
Alper Eroglu: The Jackson Laboratory for Genomic Medicine
David J. Mellert: The Jackson Laboratory for Genomic Medicine
George A. Kuchel: University of Connecticut Center on Aging, UConn Health Center
Jacques Banchereau: The Jackson Laboratory for Genomic Medicine
Duygu Ucar: The Jackson Laboratory for Genomic Medicine

Nature Communications, 2020, vol. 11, issue 1, 1-17

Abstract: Abstract Differences in immune function and responses contribute to health- and life-span disparities between sexes. However, the role of sex in immune system aging is not well understood. Here, we characterize peripheral blood mononuclear cells from 172 healthy adults 22–93 years of age using ATAC-seq, RNA-seq, and flow cytometry. These data reveal a shared epigenomic signature of aging including declining naïve T cell and increasing monocyte and cytotoxic cell functions. These changes are greater in magnitude in men and accompanied by a male-specific decline in B-cell specific loci. Age-related epigenomic changes first spike around late-thirties with similar timing and magnitude between sexes, whereas the second spike is earlier and stronger in men. Unexpectedly, genomic differences between sexes increase after age 65, with men having higher innate and pro-inflammatory activity and lower adaptive activity. Impact of age and sex on immune phenotypes can be visualized at https://immune-aging.jax.org to provide insights into future studies.

Date: 2020
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DOI: 10.1038/s41467-020-14396-9

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