ArticleJCI insight2020
Intestinal alkaline phosphatase targets the gut barrier to prevent aging.
Article in JCI insight, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers.
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Who cites it
64 citing papers in PubMed, 106 citations in OpenAlex.
- A multi-mineral intervention is associated with improved intestinal permeability in patients with ulcerative colitis: results from a pilot trial.Frontiers in medicine · 2026Trial
- The Probiotic Strain Hafnia Alvei HA4597 and Its Protein Extract Selectively Activate Membrane Digestive Enzymes of Intestinal Cells in Mice.Life (Basel, Switzerland) · 2026Article
- Gut microbiota and aging: current understanding and future perspectives.Molecular biomedicine · 2026Review
- Aging-related decline in the liver and brain is accelerated by refined diet consumption.GeroScience · 2026Article
- Tissue nonspecific and intestinal alkaline phosphatase crosstalk: a missing link in hypophosphatasia pathophysiology?Journal of translational medicine · 2026Article
- Intestinal aging-related immune dysfunction: mechanisms and interventions.Acta biochimica et biophysica Sinica · 2026Review
- Organ-Specific Regulation of Systemic Aging: Focus on the Brain, Skeletal Muscle, and Gut.Cells · 2026Review
- Bone Marrow Immunometabolic Remodeling in Osteoporosis: From Systemic Risk Factors to Precision Intervention.International journal of general medicine · 2026Review
- Gut frailty: the core of reversing frailty.Annals of medicine · 2025Article
- Alcohol, aging, and the gut microbiome: Intersections of immunity, barrier dysfunction, and disease.Alcohol (Fayetteville, N.Y.) · 2025Review
- Grape Seed Proanthocyanidins: A Potential Microbiome-Targeted Intervention for Healthy Aging in Rats.Molecular nutrition & food research · 2025Article
- CD4 T cell therapy counteracts inflammaging and senescence by preserving gut barrier integrity.Science immunology · 2025Article
- Intestinal alkaline phosphatase is a receptor for cholesterol-lowering pentapeptide IIAEK and regulates cholesterol homeostasis in mice.Scientific reports · 2025Article
- Trends in intestinal aging: From underlying mechanisms to therapeutic strategies.Acta pharmaceutica Sinica. B · 2025Review
- Deficiency of intestinal alkaline phosphatase affects behavior and microglia activity in mice.Brain, behavior, and immunity · 2025Article
- Skim Milk Culture ofCells · 2025Article
- The Impact of Rosemary and Ginger Extracts on Aging and Healthspan in Drosophila.Aging and disease · 2025Article
- Proteomic analysis across aged tissues reveals distinct signatures and the crucial involvement of midgut barrier function in the regulation of aging.Aging cell · 2025Article
- The relationship between gut microbiome and human diseases: mechanisms, predisposing factors and potential intervention.Frontiers in cellular and infection microbiology · 2025Review
- Using sodium glycodeoxycholate to develop a temporary infant-like gut barrier model,Frontiers in nutrition · 2025Article
4 more citing papers are in PubMed but not listed here.
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Authors and funding
19 authors at 2 institutions in 1 country.
Funding
Abstract
Gut barrier dysfunction and gut-derived chronic inflammation play crucial roles in human aging. The gut brush border enzyme intestinal alkaline phosphatase (IAP) functions to inhibit inflammatory mediators and also appears to be an important positive regulator of gut barrier function and microbial homeostasis. We hypothesized that this enzyme could play a critical role in regulating the aging process. We tested the role of several IAP functions for prevention of age-dependent alterations in intestinal homeostasis by employing different loss-of-function and supplementation approaches. In mice, there is an age-related increase in gut permeability that is accompanied by increases in gut-derived portal venous and systemic inflammation. All these phenotypes were significantly more pronounced in IAP-deficient animals. Oral IAP supplementation significantly decreased age-related gut permeability and gut-derived systemic inflammation, resulted in less frailty, and extended lifespan. Furthermore, IAP supplementation was associated with preserving the homeostasis of gut microbiota during aging. These effects of IAP were also evident in a second model system, Drosophilae melanogaster. IAP appears to preserve intestinal homeostasis in aging by targeting crucial intestinal alterations, including gut barrier dysfunction, dysbiosis, and endotoxemia. Oral IAP supplementation may represent a novel therapy to counteract the chronic inflammatory state leading to frailty and age-related diseases in humans.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.