A Drug for Inflammatory Conditions can Rejuvenate Blood Cells

Young blood has a rejuvenating effect when infused into older bodies, according to recent research: Aging hearts beat stronger, muscles become stronger, and thinking becomes sharper.

All blood cells in the body are created by a small number of stem cells that reside in bone marrow. Over time, these hematopoietic stem cells start to change: They produce fewer red blood cells (leading to anemia) and fewer immune cells (which raises the risk of infection and impedes vaccination efforts), and they have trouble maintaining the integrity of their genomes (which can lead to blood cancers).

Emmanuelle Passegué, PhD, director of the Columbia Stem Cell Initiative, an his team  found that an anti-inflammatory drug, already approved for use in rheumatoid arthritis, can turn back time in mice and reverse some of the effects of age on the hematopoietic system.

The researchers only identified the drug after a comprehensive investigation of the stem cells that create all blood cells and the niches where they reside in the center of the bones.

They took a closer look at the stem cells’ environment, the bone marrow. With techniques developed in the Passegué lab that enable detailed investigation of the bone marrow milieu, the researchers found that the aging niche is deteriorating and overwhelmed with inflammation, leading to dysfunction in the blood stem cells.

One inflammatory signal released from the damaged bone marrow niche, IL-1B, was critical in driving these aging features, and blocking it with the drug, Anakinra, remarkably returned the blood stem cells to a younger, healthier state.

Even more youthful effects on both the niche and the blood system occurred when IL-1B was prevented from exerting its inflammatory effects throughout the animal’s life.

The researchers are now trying to learn if the same processes are active in humans and if rejuvenating the stem cell niche earlier in life, in middle age, would be a more effective strategy.

Meanwhile, “treating elderly patients with anti-inflammatory drugs blocking IL-1B function should help with maintaining healthy blood production,” Passegué says, and she hopes the finding will lead to clinical testing.

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SOURCE:

Carl A. Mitchell, Evgenia V. Verovskaya, Fernando J. Calero-Nieto, Oakley C. Olson, James W. Swann, Xiaonan Wang, Aurélie Hérault, Paul V. Dellorusso, Si Yi Zhang, Arthur Flohr Svendsen, Eric M. Pietras, Sietske T. Bakker, Theodore T. Ho, Berthold Göttgens, Emmanuelle Passegué. Stromal niche inflammation mediated by IL-1 signalling is a targetable driver of haematopoietic ageing. Nature Cell Biology, January 17 2023; 25 (1): 30 DOI: 10.1038/s41556-022-01053-0

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