Intestinal alkaline phosphatase targets the gut barrier to prevent aging

Area of Science:

• Gastroenterology
• Aging Research
• Microbiology

Background:

• Gut barrier dysfunction and inflammation are key drivers of aging.
• Intestinal alkaline phosphatase (IAP) regulates gut barrier function and microbial balance.
• IAP's role in aging remains largely unexplored.

Purpose of the Study:

• To investigate the role of IAP in age-dependent intestinal homeostasis.
• To determine if IAP supplementation can prevent or reverse aging-related gut alterations.
• To assess IAP's impact on lifespan and frailty.

Main Methods:

• Utilized loss-of-function and oral supplementation strategies in mouse models.
• Examined gut permeability, inflammation markers, and gut microbiota composition.
• Tested IAP's effects in Drosophila melanogaster as a secondary model system.

Main Results:

• IAP-deficient mice exhibited exacerbated age-related gut permeability and inflammation.
• Oral IAP supplementation reduced gut permeability, systemic inflammation, and frailty.
• IAP supplementation extended lifespan and preserved gut microbiota homeostasis during aging.

Conclusions:

• IAP plays a critical role in maintaining intestinal homeostasis during aging.
• Oral IAP supplementation is a promising therapeutic strategy against age-related gut dysfunction and inflammation.
• IAP may counteract chronic inflammation, frailty, and age-related diseases.