'Young blood' transfusions found to reverse aging in mice

Infusing young blood into an older system may sound unfeasible, but it turns out it is now within reach. In the research paper, graduate student Carl Mitchell and Passegué found that an anti-inflammatory drug, known for its use in rheumatoid arthritis, "can turn back time in mice and reverse some of the effects of age on the hematopoietic system."

Rejuvenating old hematopoietic stem cells

A comprehensive investigation of the stem cells that create all blood cells was conducted - after which the drug was identified.

So how does this work? First things first, all the aforementioned stem cells reside in the bone marrow. Over time, these hematopoietic stem cells begin to produce fewer red blood cells (leading to anemia) and immune cells (raising the risk of infection). 

Now, in a paper published in 2021, Passegué and her team tried to rejuvenate old hematopoietic stem cells in mice with exercise or a calorie-restricting diet. It didn't work. They even transplanted old stem cells into young bone marrow, which also failed. 

Mitchell and Passegué then took a closer look at the stem cells' environment, the bone marrow. "Blood stem cells live in a niche; we thought what happens in this specialized local environment could be a big part of the problem," Mitchell said.

The answer lay in the bone marrow

The Passegué lab decided to thoroughly investigate the bone marrow. The team found that one inflammatory signal released from the damaged bone marrow niche, IL-1B, was "critical in driving aging features, and blocking it with the drug, anakinra, remarkably returned the blood stem cells to a younger, healthier state."

The researchers will now investigate 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."

"Treating elderly patients with anti-inflammatory drugs blocking IL-1B function should help with maintaining healthier blood production," Passegué said, and she hopes the finding will lead to clinical testing.

The study was published in the journal Nature Cell Biology,

Study Abstract

Haematopoietic aging is marked by a loss of regenerative capacity and skewed differentiation from hematopoietic stem cells (HSCs), leading to impaired blood production. Signals from the bone marrow niche tailor blood production, but the contribution of the old niche to hematopoietic aging remains unclear. Here we characterize the inflammatory milieu that drives both niche and hematopoietic remodeling. We find decreased numbers and functionality of osteoprogenitors at the endosteum and expansion of central marrow LepR+ mesenchymal stromal cells associated with deterioration of the sinusoidal vasculature. Together, they create a degraded and inflamed old bone marrow niche. Niche inflammation in turn drives the chronic activation of emergency myelopoiesis pathways in old HSCs and multipotent progenitors, which promotes myeloid differentiation and hinders hematopoietic regeneration. Moreover, we show how the production of interleukin-1β (IL-1β) by the damaged endosteum acts in trans to drive the proinflammatory nature of the central marrow, with damaging consequences for the old blood system. Notably, niche deterioration, HSC dysfunction, and defective regeneration can all be ameliorated by blocking IL-1 signaling. Our results demonstrate that targeting IL-1 as a key mediator of niche inflammation is a tractable strategy to improve blood production during aging.