Study sheds light on aging-induced immunodeficiency

The decline of immune function and the increase of systemic inflammation have been seen in the process of aging. But the precise mechanisms underlying these alterations remain unclear.

Now, scientists from the Jackson Laboratory for Genomic Medicine and the University of Connecticut have gained insights into this issue. They have found a new and robust aging signature in immune cells in the blood. The study, titled "The chromatin accessibility signature of human immune aging stems from CD8+ T cells," was published 13 September 2017 in the Journal of Experimental Medicine.

As a person ages, the skin becomes wrinkly, the hair turns gray, the memory declines, and the movement slows down. These changes have deep-rooted causes. Scientists want to draw a fuller picture of the aging process.

Dr. Duygu Ucar, first author of the new study, is an associate professor at the Jackson Laboratory for Genomic Medicine. The laboratory of Dr. Ucar aims to develop computational models to study the dynamics of transcriptional gene regulation and identify potential strategies for genomic medicine.

In this work, Dr. Ucar and co-workers collected blood samples from young and old people. They isolated immune cells from the samples, and then analyzed gene activation in these cells. The analyses revealed a new and robust aging signature in these immune cells. First, regions of chromosomes that contain genes critical for T-cell signaling are more likely to be closed in the old in comparison with the young. In contrast, regions of chromosomes that contain genes involved in cell death and inflammation are more likely to be open in the old, as compared with the young. Additionally, the study showed that the inactivation of IL7R and other genes in the IL-7 signaling pathway may be a biomarker of aging-induced immunodeficiency.

Chromosomes, which are composed of DNA and proteins and are located in the cell nucleus, carry heredity information that an organism needs to survive. Chromosomes can be divided into open and closed regions. Genes in open chromosome regions are preferentially expressed to make proteins because the DNA is open to entry of molecular machinery. By contrast, genes in closed chromosome regions are not expressed. The dynamic conversion between open and closed regions controls gene expression.

According to George Kuchel, senior author of the study and professor of medicine at the University of Connecticut, the open chromosome regions and the closed chromosome regions are different between young and old people.

Collectively, the study sheds light on why old people experience decreased immune function and increased systemic inflammation. It appears that like the skin, chromosomes within cells wrinkle with age, leading to deficiencies in immune responses. Additionally, the study offers a unique approach to identifying biomarkers of aging-related immunodeficiency.
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