AI has identified the aging gene in hematopoietic cells

Bone marrow stem cells have a unique property: they can both self‑replicate and differentiate into any type of blood cell. Throughout life, they constantly replenish losses caused by infections, bleeding, or chemotherapy. However, their effectiveness declines with age. The number of stem cells increases, but the ability to restructure the circulatory system decreases, which can lead to anemia, weakened immunity, thrombosis, and age‑related blood disorders.

By analyzing individual hematopoietic stem cells from mice of different ages, researchers found that two genetic programs are simultaneously activated in older cells: one keeps them in an immature stem cell state, and the other prepares them for the production of platelets. These changes begin gradually; the immaturity program intensifies even before birth, while the genes associated with platelets become active afterward. This means that the aging of stem cells develops continuously and does not appear suddenly in old age.

To identify the genes that control this process, the team used Geneformer — an AI model trained on gene expression data from approximately 1 million cells. Additional training was carried out on 160,000 young and old hematopoietic stem and progenitor cells. The AI predicted 143 promising candidates, which were then tested in the laboratory and reduced to one key regulator — Pbx1.

It turned out that Pbx1 in old stem cells is closely linked to genes associated with immaturity, aging, and platelet production. Increasing Pbx1 in young cells reproduced many signs of aging: up to 73.3% of the genes activated by Pbx1 were also upregulated in old stem cells. After transplantation into mice, such cells produced fewer red blood cells and relatively more platelets. The reason for the reduced red blood cell production, as it turned out, was the suppression of another gene by Pbx1 — Gata1.

As the study’s author, Keiye Takubo, notes, old blood stem cells are often described simply as cells that have lost their function. But the results show that they are not a weakened version of younger cells — they are cells that have transitioned to a different, stable state with their own tendencies. Future research should show whether the same mechanism works in humans and whether it is associated with anemia, thrombosis, clonal hematopoiesis, or blood cancer.