Study identifies key blood stem cells in immune system aging

Rong Lu, associate professor of stem cell biology and regenerative medicine, biomedical engineering, medicine, and gerontology at USC, and a Leukemia & Lymphoma Society ScholarOur study provides compelling evidence that when a small subset of blood stem cells overproduces innate immune cells, this drives the aging of the immune system, contributes to disease, and ultimately shortens the lifespan."

In the study, first author Anna Nogalska and her colleagues found striking differences in how quickly the immune system ages-;even among lab mice with the same genetic background raised in identical conditions. By the advanced age of 30 months, delayed aging mice retained a youthful balance of innate and adaptive immune cells. However, early aging mice showed a big increase in innate immune cells relative to adaptive immune cells.

By tracking the individual blood stem cells responsible for producing both innate and adaptive immune cells, the scientists discovered the subset of blood stem cells primarily responsible for the age-associated imbalance of the immune system. Specifically, the scientists observed that thirty to forty percent of blood stem cells dramatically changed their preference for producing innate versus adaptive immune cells as the mice aged.

In delayed agers, the subset of blood stem cells decreased their production of innate immune cells, protecting against the effects of aging. Among delayed agers, there was an increase in gene activity related to blood stem cells' regulation and response to external signals-;which might keep their production of innate immune cells in check. When the scientists used CRISPR to edit out these genes, blood stem cells reversed their natural tendency and produced more innate immune cells instead of adaptive immune cells-;like in the early agers.

In contrast, in early agers, the subset of blood stem cells shifted towards producing more innate immune cells, which, in excess, lead to many diseases of aging. Accordingly, in these early agers, the scientists found an increase in gene activity related to the proliferation of blood stem cells and the differentiation of innate immune cells. When the scientists used CRISPR to edit out these early aging genes, blood stem cells produced more adaptive immune cells instead of innate immune cells-;becoming more similar to those in the delayed agers.

Importantly, delayed agers tended to live longer than early agers.

Source:

Keck School of Medicine of USC

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