Blood stem cells drive chronic inflammation in aging

As organisms age, the blood-forming system changes. Stem cells in the bone marrow, which give rise to all blood cells, begin to behave differently. A new study published in Nature Aging shows that a protein called SIRT3 plays a key role in this shift. SIRT3 regulates the function of mitochondria, the energy-producing structures inside cells.

Trained immunity gone wrong

The immune system can become ‘trained’ by past exposures, retaining a heightened readiness to respond. In young, healthy individuals, this is broadly beneficial. But in aging, that training can become dysregulated. The researchers showed in mice that reduced SIRT3 activity causes blood stem cells to develop a form of maladaptive trained immunity. These stem cells produce more inflammation-promoting immune cells, particularly certain white blood cells known as myeloid cells.

Those pro-inflammatory cells then circulate through the body and cause tissue damage. In the mice studied, this led to measurable functional decline in organs. The mitochondria within the blood stem cells also showed poorer performance when SIRT3 activity was reduced.

From bone marrow to body-wide inflammation

What makes this study notable is the proposed direction of causality: not a diseased organ generating inflammation, but the blood stem cells themselves acting as a source. SIRT3 appears to act as a brake on this process. Without it, stem cells become programmed to generate more inflammatory cells than needed in response to any stimulus.

Whether the same mechanisms apply in humans has not yet been established. The findings nonetheless align with prior work linking blood stem cell aging to rising risks of cardiovascular and other age-related diseases. From a longevity perspective, the suggestion that trained immunity drives aging-related inflammation opens potential avenues involving SIRT3 or mitochondrial function in stem cells, though that has not been tested in this study.

Read the original article