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Assessing Lysosomal Alkalinization in the Intestine of Live Caenorhabditis elegans
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Supplementation with Brush Border Enzyme Alkaline Phosphatase Slows Aging
James W Larrick1,2, Andrew R Mendelsohn1,2
1Panorama Research Institute, Sunnydale, California.
Rejuvenation Research
|April 8, 2020
Summary
Intestinal alkaline phosphatase (IAP) declines with age, impairing gut integrity. Supplementing IAP in mice and flies improved gut health, reversed aging signs, and extended lifespan, suggesting therapeutic potential.
Area of Science:
- Gastroenterology
- Aging Research
- Immunology
Background:
- Diminished intestinal epithelial barrier integrity is linked to aging-associated dysfunction and inflammaging.
- Intestinal alkaline phosphatase (IAP) expression decreases with age in mice and humans.
- IAP deficiency leads to liver inflammation and reduced lifespan in mice.
Purpose of the Study:
- To investigate the role of IAP in maintaining gut integrity and its potential as a therapeutic target for aging.
- To determine if IAP supplementation can ameliorate age-related gut dysfunction and extend lifespan.
Main Methods:
- Studies in mice and flies involving IAP deficiency, IAP supplementation, and dietary IAP induction.
- Assessment of gut barrier function, microbiome composition, metabolic parameters, and lifespan.
- Analysis of tight junction protein expression and bacterial pro-inflammatory factor inactivation.
Main Results:
- Exogenous IAP supplementation reversed age-induced gut barrier dysfunction, improved metabolic health, prevented microbiome dysbiosis, and extended lifespan in mice.
- Increased dietary IAP enhanced physical performance in aging flies.
- IAP maintains gut integrity by supporting tight junction proteins and dephosphorylating lipopolysaccharides (LPS).
Conclusions:
- IAP plays a critical, conserved role in maintaining intestinal barrier integrity and combating aging-associated pathologies.
- Increasing IAP levels, either exogenously or endogenously, shows promise for slowing aging and treating age-related diseases.
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