Aging Blood Stem Cells May Drive Systemic Inflammation, Study Finds

Researchers published in *Nature Aging* investigated whether aging blood-forming stem cells (hematopoietic stem cells) merely reflect organismal aging or actively promote decline in distant tissues. The team focused on the mitochondrial protein SIRT3, whose levels fall with age in both mouse and human stem cells. Genetically modified mouse stem cells engineered to overexpress SIRT3 were transplanted into young mice whose immune systems had been compromised. The recipients were monitored until they reached two years of age—a senior stage for mice. Compared with mice receiving unaltered stem cells, those with SIRT3-enhanced cells showed fewer inflammation-promoting immune cells, ran farther, clung longer to an inverted screen, performed better on memory tests, maintained tighter blood-sugar control, and displayed healthier lung tissue. A second experiment transferred only the immune cells derived from the SIRT3-boosted stem cells into separate young mice, which likewise exhibited improved muscle function, glucose regulation, and lung structure.

ScienceAlert

Further analysis indicated that SIRT3 helps prevent stem cells from becoming locked into a pattern that overproduces pro-inflammatory immune cells. By weakening this pattern, higher SIRT3 levels reduced chronic, low-grade inflammation that can damage tissues over time. The experiments therefore suggest that age-related changes in blood stem cells can propagate inflammatory signals to remote organs via the immune cells they generate.

ScienceAlert

Senior author Danica Chen of the University of California, Berkeley, emphasized that the key next step is to determine whether the mouse mechanism operates in humans. She noted that while the mouse data reveal a causal link between stem-cell aging and systemic inflammation, the findings do not yet demonstrate that boosting SIRT3 can slow human aging, extend lifespan, or serve as a therapeutic approach.

ScienceAlert

• “The first question is whether the mechanism we identified in mice is conserved in humans,” — Danica Chen, author and biologist

ScienceAlert

The study adds to growing evidence that the hematopoietic system plays a broader role in organismal aging than previously recognized. However, the work was conducted exclusively in mice using genetically altered stem cells, and the bone-marrow transplantation process itself may have influenced outcomes. Consequently, researchers caution against extrapolating the results to humans until studies confirm that declining SIRT3 activity similarly drives inflammatory immune profiles in aging people. If validated, targeting blood stem cells could become a strategy for mitigating age-related inflammation across multiple organs.

ScienceAlert