Could We Slow Aging by Rejuvenating Old Blood Stem Cells?

A new study has found that an anti-inflammatory drug used for rheumatoid arthritis can revitalize and overturn some of the effects of aging on the blood system in mice. The study is published in Nature Cell Biology.

Aging blood systems

Previous research in mice has shown that blood from young bodies may have rejuvenating and restorative effects when added to older bodies. Older hearts and muscles increase in strength while cognitive skills are sharpened [Updated February 13, 2023].

“An aging blood system, because it’s a vector for a lot of proteins, cytokines and cells, has a lot of bad consequences for the organism,” said Dr. Emmanuelle Passegué, senior author of the study and director of the Columbia Stem Cell Initiative. “A 70-year-old with a 40-year-old blood system could have a longer healthspan, if not a longer lifespan.”

Scientists are now looking to identify if some of the benefits of young blood could be targeted and replicated with medication. In their study, Passegué and colleagues found that rejuvenating the body’s system that produces blood may be a viable option.

“These results indicate that such strategies hold promise for maintaining healthier blood production in the elderly,” said graduate student and lead author Carl Mitchell.

Giving blood cell production a new lease on life

The researchers identified the effects of the drug anakinra – already approved for the treatment of rheumatoid arthritis – after analyzing the blood cell-producing (hematopoietic) stem cells in our bone marrow.

All blood cells are produced by hematopoietic stem cells, but these can become affected by age over time. Gradually, they produce fewer red and white blood cells which can lead to anemia and increased risk of infection. Their ability to protect their DNA from errors can also become impaired, increasing the risk of blood cancers.

Previous attempts by Passegué and colleagues to revitalize hematopoietic stem cells in mice – including through exercise, calorie-restrictive diets and transplants of young stem cells into bone marrow – have all failed to produce the desired effects.

In the current study, the researchers investigated the environment – or niche – that the stem cells are found in, instead of the cells themselves. “Blood stem cells live in a niche; we thought what happens in this specialized local environment could be a big part of the problem,” said Mitchell.

They found evidence of inflammation and deterioration in the aging hematopoietic stem cell niche that could be responsible for their loss of function. For example, the inflammatory signal interleukin-1 beta (IL-1B) was released from the damaged niche and promoted the features of aging. Giving these mice the rheumatoid arthritis drug anakinra, which blocks the action of IL-1B, returned their blood stem cells to a much healthier state.

Treating human patients?

Next, the research team wants to find out if the same process could also work in humans in clinical testing, and if improving the health of the stem cell niche earlier in life, such as in middle age, could have even more youthful rejuvenating effects.

“We know that bone tissue begins to degrade when people are in their 50s. What happens in middle age? Why does the niche fail first?” Passegué said. “Only by having a deep molecular understanding will it be possible to identify approaches that can truly delay aging.”

Reference: Mitchell CA, Verovskaya EV, Calero-Nieto FJ, et al. Stromal niche inflammation mediated by IL-1 signalling is a targetable driver of haematopoietic ageing. Nat Cell Biol. 2023;25(1):30-41. doi: 10.1038/s41556-022-01053-0

This article is a rework of a press release issued by the Columbia University Irving Medical Center. Material has been edited for length and content.

Correction

The article previously stated that previous studies were performed using blood from people, this was updated on February 13, 2023 to correctly identify the studies were in mice.