Aging-Dependent Hepatic YAP1 Reduction Promotes Metabolic Dysfunction-Associated Steatotic Liver Disease via Gut Microbiota Dysbiosis With Akkermansia muciniphila Downregulation - PubMed
5 hours ago
- #liver aging
- #gut microbiota
- #YAP1
- Aging leads to progressive liver dysfunction and increased risk of metabolic dysfunction-associated steatotic liver disease (MASLD).
- Hepatic YAP1 expression decreases with age, and its loss accelerates liver aging, causing increased senescence, impaired proliferation, and DNA damage.
- YAP1 deficiency activates the cGAS-STING pathway, increases oxidative stress and triglyceride accumulation, leading to MASLD.
- Loss of YAP1 disrupts gut microbiota composition, particularly reducing Akkermansia muciniphila abundance, and impairs intestinal barrier function.
- Microbiota depletion reverses Yap1 deletion-induced senescence and MASLD, while A. muciniphila supplementation improves gut barrier integrity and alleviates MASLD symptoms.
- The study highlights the YAP1-gut microbiota axis as a potential therapeutic target for aging-related liver diseases.