Researchers utilizing artificial intelligence have pinpointed a key genetic control point responsible for aging in blood stem cells. The findings, published in Science Advances on August 22, 2026, shed new light on the molecular mechanisms that cause blood production to become unbalanced over time.
AI Identifies Key Gene Driving Stem-Cell Aging
Stem cells possess the unique ability to self-renew and transform into different types of cells. Rare hematopoietic stem cells found in bone marrow can become any type of blood cell, producing new cells throughout life to replace those lost because of infection, bleeding, or chemotherapy. However, as people and animals age, hematopoietic stem cells become less effective. Their numbers increase, but their ability to rebuild the blood system declines, contributing to conditions such as anemia, reduced immunity, blood clots, and age-related blood disorders.
Single-Cell Analysis Reveals Continuous Aging Process
To understand how this decline unfolds, researchers at Tohoku University analyzed individual hematopoietic stem cells from mice of different ages. The team discovered that aged stem cells simultaneously activate two distinct gene programs: one that preserves a highly immature stem-cell state and another that prepares the cells to produce platelets.
These changes begin gradually, with the immature program increasing before birth and platelet-related genes increasing after birth. According to the study, this indicates that stem-cell aging develops continuously rather than appearing suddenly in old age.
Geneformer AI Model Narrows Down 143 Candidates
To identify the specific genes controlling this biological shift, the team utilized Geneformer, an artificial intelligence model trained on gene-expression data from about 30 million cells. Researchers further trained the model using approximately 160,000 young and aged blood stem and progenitor cells. The AI was tasked with predicting which genes could shift young stem cells toward an aged state.
AI helped us find 143 promising candidates, which we then screened in the lab and narrowed down to a key control point of aging: a gene-regulating factor called Pbx1,
said Keiyo Takubo of Tohoku University, as reported by News Medical.
Laboratory Screening and Transplantation Experiments
In aged stem cells, Pbx1 was found to be strongly connected to genes involved in stem-cell immaturity, aging, and platelet production. When researchers increased Pbx1 in young stem cells, it successfully reproduced many features of aged cells. Up to 73.3% of the genes activated by Pbx1 were also increased in naturally aged stem cells.
After transplantation into mice, these modified cells produced fewer red blood cells and showed a relative increase in platelet production. The researchers proposed that part of the reason for the reduced red blood cell development was Pbx1 suppressing another gene called Gata1.
Aged blood stem cells are often described simply as cells that have lost function,
Takubo said, according to coverage by The National Tribune. But our findings show that they aren’t a weaker version. They just enter a different, stable state with their own tendencies.
Future Directions and Implications
The research combines AI prediction, large-scale screening, multi-omics analysis, and transplantation experiments to reveal key points of the pathway leading to hematopoietic stem cell aging. Future studies will aim to determine whether this same mechanism operates in humans and whether it contributes to conditions such as anemia, thrombosis, clonal hematopoiesis, or blood cancers.
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