In a discovery that could reshape our findings of age-related blood diseases, the researchers identified a bacterial metabolite that flows into the bloodstream as it ages and accelerates the growth of potentially dangerous pre-leukocyte cells.
Scientists from multiple research institutions have found that substances produced only by Gram-negative bacteria in the gut appear in the blood of older people and promote the expansion of mutated blood stem cells – a disease called the disease of clonal hematoma with uncertain potential (CHIP).
CHIP is estimated to affect 10-20% of people over the age of 70 and greatly increases the risk of hematologic cancer and cardiovascular disease. Although only a small percentage of individuals with chips flow to leukemia, the strongest predictor of this progression is the accumulation of these mutant blood cells.
This study published in nature shows that age-related changes in the intestinal wall allow this bacterial metabolite to penetrate into the cycle in which ready-made targets in star cells were found.
“Although there is a known association between chips and increased mortality, our understanding of environmental and regulatory factors in this process during aging remains fundamental,” the researchers wrote in the paper.
What makes this discovery particularly interesting is the mechanism involved. The team found that leukocyte cells with mutations in the DNMT3A gene expressed higher levels of Alpk1, the only known ADP-induced receptor in human cells. When Adp-Heptos binds to this receptor, it triggers changes, giving the mutated cells a competitive advantage over healthy cells.
The research team confirmed the process through multiple laboratory experiments. When they transplanted DNMT3A mutated hemostem cells into mice and then exposed them to ADP-Heptose, the mutated cells were significantly multiplied and all exceeded normal cells. This advantage disappeared completely when they genetically remove the ALPK1 receptor.
The meaning goes beyond blood disorders. The researchers found that ADP calorie levels in CHIP patients were associated with higher rates of hypertension and venous thromboembolism, suggesting that the bacterial product may contribute to cardiovascular risks already associated with CHIP.
Dr. Daniel Starczynowski, one of the authors of the study, believes that the findings may open up new therapeutic possibilities. If scientists can develop methods to block ADP-Heptose-Alpk1 interactions, they may prevent CHIP from developing into leukemia or reduce its associated inflammatory conditions.
This work connects several important biological areas of aging, gut health, inflammation and cancer, and serves as an increasing recognition that our microbiome affects health in ways far beyond the digestive system.
As the population ages globally, it becomes increasingly important to understand the specific mechanisms driving age-related diseases. This study shows that maintaining intestinal barrier integrity may be another important factor in healthy aging and cancer prevention strategies.
If our report has been informed or inspired, please consider donating. No matter how big or small, every contribution allows us to continue to provide accurate, engaging and trustworthy scientific and medical news. Independent news takes time, energy and resources – your support ensures that we can continue to reveal the stories that matter most to you.
Join us to make knowledge accessible and impactful. Thank you for standing with us!
