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Fighting aging-associated clonal hematopoiesis with microbial metabolite
Shuqin Zeng1, Dezhi Mu1, Shaopu Wang1
1Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu 610041, China; Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu 610041, China.
Trends in Molecular Medicine
|June 18, 2025
Summary
Age-related clonal hematopoiesis in elderly is driven by gut microbial changes. Specific bacteria release ADP-heptose, activating ALPK1 signaling and promoting pre-leukemic cell growth.
Area of Science:
- Hematology
- Microbiology
- Immunology
Background:
- Age-related clonal hematopoiesis involves expansion of pre-leukemic cells.
- The underlying mechanisms driving this expansion in the elderly are not fully understood.
Purpose of the Study:
- To investigate the role of gut microbiota in age-related clonal hematopoiesis.
- To elucidate the signaling pathways involved in pre-leukemic cell expansion.
Main Methods:
- Analysis of gut microbial composition in elderly individuals.
- Detection of microbial metabolites in systemic circulation.
- Investigation of the ALPK1 signaling pathway in hematopoietic cells.
Main Results:
- Elderly individuals show gut microbial dysbiosis with increased Gram-negative bacteria.
- These bacteria release ADP-heptose into circulation.
- ADP-heptose promotes pre-leukemic cell expansion via ALPK1-dependent signaling.
Conclusions:
- Gut microbial dysbiosis contributes to age-related clonal hematopoiesis.
- ADP-heptose and ALPK1 signaling represent a novel mechanism linking gut health to blood cancer precursors.
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