Will revitalizing old blood slow aging?

Young and old blood stem cells. Renewing the stem cells that create all blood cells can slow aging. Credit: Emmanuelle Passegué

New blood has a rejuvenating effect when introduced into aging bodies, according to recent research: aging hearts beat faster, muscles become stronger and thinking becomes sharper.

Many scientists are looking for new blood elements that can be captured or replicated and put into a pill.

But what if the best way to get the benefits of new blood is to simply renew the system that produces the blood?

“An aging blood system, because it is a vector for many proteins, cytokines and cells, has many bad consequences for the organism,” says Emmanuelle Passegué, Ph.D., director of the Columbia Stem Cell Initiative, which is studying how blood changes with age. “A 70-year-old with a 40-year-old blood system can have a longer health life expectancy, if not a longer life.”

Rejuvenating an elderly person’s blood may now be within reach, based on recent findings from Passegué’s lab published in Nature Cell Biology.

Passegué, with her graduate student Carl Mitchell, found that an anti-inflammatory drug, already approved for use in rheumatoid arthritis, could turn back time in mice and reverse some of the effects of age on the hematopoietic system.

“These results show that such strategies hold promise for maintaining healthier blood production in the elderly,” says Mitchell.

Renewal of the home of blood stem cells. The researchers found that an inflammatory signal released by old bone marrow, IL-1B, was critical in inducing aging in blood stem cells. The drug anakinra returned the blood stem cells to a younger, healthier state. Credit: Emmanuelle Passegué Returning blood stem cells to a younger state

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

All blood cells in the body are created from a small number of stem cells that reside in the bone marrow. Over time, these hematopoietic stem cells begin to change: they produce fewer red blood cells (leading to anemia) and fewer immune cells (which increases the risk of infection and hinders vaccination efforts), and they have difficulty maintaining the integrity of their genome. which can lead to blood cancer).

In a paper published in 2021 in the Journal of Experimental Medicine, Passegué and her team first tried to rejuvenate old hematopoietic stem cells in mice with exercise or a calorie-restricted diet, both of which are generally thought to slow down the process. aging. Neither worked. Transplantation of old stem cells into new bone marrow also failed. Even the new blood had no effect on the renewal of the old blood stem cells.

Mitchell and Passegué then took a closer look at the stem cell environment, the bone marrow. “Blood stem cells live in one place; we thought what happens in this specialized local environment might be a big part of the problem,” says Mitchell.

With techniques developed in the Passegué laboratory that enable a detailed investigation of the bone marrow environment, the researchers discovered that the aging joint is deteriorating and overwhelmed with inflammation, leading to dysfunction in the blood stem cells.

An inflammatory signal released by the damaged bone marrow, 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 state. and healthier.

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

Researchers are now trying to learn whether the same processes are active in humans and whether rejuvenating the stem cell pool earlier in life, in middle age, would be a more effective strategy.

Meanwhile, “treating elderly patients with anti-inflammatory drugs that block IL-1B function should help maintain healthier blood production,” says Passegué, and she hopes the discovery will lead to clinical trials.

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

Many societies have added more than 30 years to life expectancy in the past century. “It is now imperative to turn to science to determine how to create health and well-being throughout those lives,” says Linda Fried, MD, MPH, dean of Columbia University’s Mailman School of Public Health and director of the Center for Aging Butler Columbia. “This must include research to understand the mechanisms of normal aging and how to fully develop the great opportunities to create healthy longevity for all.”

More information: Carl A. Mitchell et al, Stromal niche inflammation mediated by IL-1 signaling is a targeted inducer of hematopoietic senescence, Nature Cell Biology (2023). DOI: 10.1038/s41556-022-01053-0

Provided by Columbia University

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