Bones do more than hold your body upright.
Inside many of them is a living factory that constantly produces the cells that make up your blood and immune system: bone marrow.
Immune cells produced there enter the bloodstream and travel to the muscles, lungs, brain, and other organs. This means that when the stem cells producing them grow old, the effects may not remain inside the bones.
A new study published in Nature Aging suggests that aging blood stem cells can contribute to signs of aging elsewhere in the body by producing immune cells that promote inflammation.
Inflammation is normally a short-term defense against infection and injury. But when it persists at a low level for years, it can damage healthy tissues.
The researchers wanted to answer an important question: Do aging blood stem cells merely reflect aging, or can they actively contribute to decline in distant organs?
The team focused on a protein called SIRT3, which helps the energy-producing structures inside cells function properly and cope with stress. SIRT3 levels decline with age in the blood stem cells of both mice and humans.
The researchers used genetically altered blood stem cells from mice, designed to produce more SIRT3. They then transplanted either these cells or unaltered stem cells into young mice with damaged immune systems, with the transplants rebuilding the animals' blood and immune systems.
The mice were followed until they reached two years of age, which is old for these animals. Mice carrying the SIRT3-boosted stem cells had fewer immune cells that promoted inflammation.
The differences extended beyond their blood. These mice ran farther, held on to an inverted screen for longer, performed better in a memory test, controlled their blood sugar more effectively, and had healthier-looking lungs.
But the transplant experiment alone could not reveal whether immune cells produced by the altered stem cells carried those effects to distant tissues. So the team went a step further.
The researchers transferred immune cells produced by the SIRT3-boosted stem cells into other young mice. These animals also showed better muscle function, blood sugar control, and lung structure.
"The strongest evidence comes from our transplantation and adoptive transfer experiments," senior author and biologist Danica Chen from University of California, Berkeley told ScienceAlert.
Together, the two experiments suggested that changes beginning in blood stem cells could reach distant organs through the immune cells they produced.
Further analyses suggested that SIRT3 helps prevent blood stem cells from becoming locked into a pattern of producing too many inflammation-promoting immune cells. Increasing the protein appeared to weaken this harmful pattern.
The findings add to evidence that the blood-making system may play a wider role in aging than previously recognized.
Scientists have previously restored aging blood stem cells to a more youthful state in mice. Research involving different human populations also suggests that long-term inflammation may not be an unavoidable part of growing older.
There are important reasons for caution. The experiments were conducted in mice using genetically altered stem cells, and the preparation required before bone marrow transplantation may itself have affected the animals.
The study examined selected measures of health, and does not show that increasing SIRT3 can slow aging, extend life, or improve health in people.
But it raises some interesting questions.
"The first question is whether the mechanism we identified in mice is conserved in humans," Chen said.
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Researchers must now determine whether declining SIRT3 activity causes aging human blood stem cells to produce more inflammation-promoting immune cells. Until that connection is established, SIRT3 remains a subject for further research, rather than a treatment for aging.
If the same process is confirmed in humans, blood stem cells could one day become a target for reducing age-related inflammation across the body.
For now, the study reveals something more fundamental: in mice, aging blood stem cells did not merely reflect decline elsewhere.
Through the immune cells they produced, they actively contributed to it.
The study was published in Nature Aging.
This article was fact-checked by Rachel Garner and edited by Peter Dockrill. While we pride ourselves on our process, we are only human. If you spot a mistake, please let us know.