Aging blood stem cells ignite chronic inflammation
Your immune system remembers past threats so it can respond faster next time. But with age, that memory can go wrong. Blood stem cells start firing up the immune system even without a real threat, fuelling chronic inflammation.
The immune system has a form of memory called trained immunity: after an infection, it responds more rapidly to the same pathogen. That sounds useful. But the study, published in Nature Aging, shows this mechanism can become harmful with age. Blood stem cells (hematopoietic stem cells) that are exposed to chronic low-grade signals become permanently primed. They continuously produce pro-inflammatory immune cells, even without any infection.
SIRT3 as a molecular brake
The researchers identified a protein called SIRT3 as a key brake on this process. SIRT3 sits in the mitochondria, the cell’s energy-producing structures, and keeps blood stem cell activity balanced. As we age, SIRT3 levels in these cells decline. Without this brake, stem cells can shift into a state of persistent, low-grade activation. The researchers describe this as maladaptive trained immunity: a protective mechanism that turns into a source of damage.
Chronic inflammation as an engine of aging
Chronic low-grade inflammation is linked in many studies to conditions such as cardiovascular disease, type 2 diabetes and cognitive decline. This research adds a specific mechanism to that picture: aging blood stem cells that use their immune memory to fuel inflammation themselves. Whether preserving SIRT3 in humans also reduces inflammation has not yet been demonstrated. The findings are based on cell studies and animal models. Still, SIRT3 offers a direction for future research into reducing inflammation during aging.
Want to research this yourself?
Search for example:
- trained immunity hematopoietic stem cells
- SIRT3 mitochondria aging
- inflammaging chronic activation