Blood Stem Cells and SIRT3 May Drive Ageing Through Inflammation

Bones serve purposes beyond simply supporting the body.

Many contain bone marrow: living tissue that continually makes the cells forming the blood and immune systems.

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

Blood stem cells, SIRT3 and inflammation

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

Inflammation is ordinarily a temporary protective response to infection or injury. Yet if it continues at a low level for years, it can harm healthy tissue.

The researchers set out to address a key question: are ageing blood stem cells simply a marker of ageing, or can they actively drive deterioration in faraway organs?

When stem cells grow old, the effects may not remain inside the bones. (master1305/iStock/Getty Images)

Their investigation centred on SIRT3, a protein that helps cells’ energy-producing structures operate properly and manage stress. Levels of SIRT3 fall with age in blood stem cells from both humans and mice.

Using genetically modified mouse blood stem cells engineered to make extra SIRT3, the researchers transplanted either these cells or unchanged stem cells into young mice with impaired immune systems. The transplants reconstituted the animals’ blood and immune systems.

The animals were monitored until they were two years old, an advanced age for mice. Those given SIRT3-enhanced stem cells had fewer immune cells that promote inflammation.

Effects of SIRT3-boosted stem cells across the body

The effects were not limited to the blood. These mice ran longer distances, gripped an inverted screen for more time, did better in a memory assessment, regulated blood sugar more effectively and had lungs that appeared healthier.

However, the transplantation experiment by itself could not establish whether immune cells generated by the modified stem cells transported those effects to distant tissues. The researchers therefore took the work further.

They transferred immune cells made by the SIRT3-boosted stem cells into another group of young mice. These animals likewise displayed improved muscle performance, blood-sugar regulation 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, the experiments indicated that alterations starting in blood stem cells could influence remote organs through the immune cells those stem cells produced.

Additional analysis indicated that SIRT3 helps stop blood stem cells becoming fixed in a pattern of making excessive numbers of inflammation-promoting immune cells. Raising levels of the protein seemed to reduce this damaging pattern.

The results contribute to growing evidence that the blood-forming system may have a broader part in ageing than was formerly understood.

Scientists have previously returned ageing blood stem cells to a more youthful state in mice. Studies involving different human populations likewise suggest that long-term inflammation may not be an inevitable aspect of getting older.

Why the mouse findings require caution

There are significant grounds for caution. The experiments used genetically modified stem cells in mice, while the preparation needed before bone-marrow transplantation could itself have influenced the animals.

The research assessed particular health measures, rather than demonstrating that increasing SIRT3 can slow ageing, lengthen life or improve health in people.

Nevertheless, it poses some intriguing 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 must next establish whether reduced SIRT3 activity makes ageing human blood stem cells produce more inflammation-promoting immune cells. Unless that link is confirmed, SIRT3 is a topic for additional research, not an anti-ageing treatment.

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

For the moment, the study shows something more basic: in mice, ageing blood stem cells were not merely reflecting decline elsewhere.

Via the immune cells they generated, 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. Although we take pride in our process, we are only human. If you spot an error, please let us know.