Aging Blood Stem Cells May Drive Inflammation Across the Body

Bones have a purpose beyond keeping the body supported.

Within many bones lies bone marrow, a living production centre that continually makes the cells forming the blood and immune system.

The immune cells generated there enter the bloodstream, reaching the muscles, lungs, brain and other organs. Consequently, when the stem cells that make them age, their effects may extend well beyond the bones.

How aging blood stem cells may affect the body

A new study published in Nature Aging indicates that ageing blood stem cells may help drive signs of ageing in other parts of the body by creating immune cells that encourage inflammation.

Inflammation usually serves as a temporary defence against injury and infection. However, when low-level inflammation continues for years, it may harm otherwise healthy tissue.

The researchers set out to address a key question: do ageing blood stem cells simply mirror ageing, or can they directly help cause deterioration in organs far from where they originate?

The researchers concentrated on SIRT3, a protein that supports the proper operation of cells' energy-producing structures and helps them manage stress. Levels of SIRT3 fall with age in blood stem cells from both humans and mice.

SIRT3-boosted blood stem cells in mice

The team used genetically modified blood stem cells from mice that had been engineered to make extra SIRT3. They transplanted either these cells or unmodified stem cells into young mice with impaired immune systems; the transplanted cells then rebuilt the animals' blood and immune systems.

The mice were monitored until the age of two years, an advanced age for the species. Those given the SIRT3-boosted stem cells had fewer immune cells that encouraged inflammation.

The effects were not confined to the blood. These animals ran further, gripped an inverted screen for longer, scored better in a memory test, regulated blood sugar more successfully and had lungs that appeared healthier.

Yet the transplantation experiment by itself could not determine whether immune cells made by the altered stem cells had carried these effects into distant tissues. The researchers therefore took the investigation further.

They transferred immune cells generated by the SIRT3-boosted stem cells into separate young mice. These recipients likewise displayed improved muscle performance, 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.

Taken together, these experiments indicated that alterations starting in blood stem cells could affect distant organs through the immune cells they produced.

Additional analyses indicated that SIRT3 helps stop blood stem cells becoming fixed in a tendency to produce excessive numbers of inflammation-promoting immune cells. Raising the protein's levels seemed to reduce this damaging tendency.

What the findings do and do not show

The results add to evidence that the blood-producing system could have a broader role in ageing than previously understood.

Scientists have previously returned ageing blood stem cells to a more youthful condition in mice. Studies involving distinct human populations also suggest that long-term inflammation may not be an inevitable feature of ageing.

There are significant grounds for caution. These experiments took place in mice and used genetically modified stem cells, while the preparation necessary for bone marrow transplantation could itself have influenced the animals.

The research assessed selected health measures and does not establish that boosting SIRT3 can delay ageing, lengthen life or improve health in people.

Still, it prompts several interesting questions.

"The first question is whether the mechanism we identified in mice is conserved in humans," Chen said.

Related: A Common Blood Pressure Drug Boosts Lifespan And Slows Aging in Animals

Researchers now need to establish whether lower SIRT3 activity makes ageing human blood stem cells produce greater numbers of inflammation-promoting immune cells. Unless that link is demonstrated, SIRT3 is a subject for further study rather than an anti-ageing treatment.

Should the same mechanism be verified in people, blood stem cells might eventually offer a target for reducing age-related inflammation throughout the body.

For the moment, the study points to a more fundamental finding: in mice, ageing blood stem cells were not merely reflecting decline occurring elsewhere.

Via the immune cells they made, they actively helped drive 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.