Alamandine/MrgD Pathway Modulates Gut-Bone Marrow Axis in Aging

Area of Science:

• Aging research
• Gastroenterology
• Immunology

Background:

• Aging is linked to compromised colon epithelial barrier integrity and increased bone marrow (BM) myelopoiesis.
• Alamandine (Ala) and MrgD are novel components of the renin-angiotensin system (RAS).
• The gut-bone marrow (BM) axis plays a crucial role in aging-related physiological changes.

Purpose of the Study:

• To investigate if Alamandine (Ala) can restore colon epithelial barrier integrity in aging mice.
• To determine if Ala modulates the gut-BM axis to achieve these effects.
• To explore Ala's impact on the gut microbiome and immune cell populations.

Main Methods:

• Aging mice (22-24 months) and young mice (2-3 months) were treated with saline or Ala.
• Intestinal permeability was assessed using FITC-dextran.
• Colon epithelial stem cells (ISCs), Wnt3a, β-catenin, fecal microbiome, and monocyte-macrophages were analyzed.

Main Results:

• Ala treatment reversed increased intestinal permeability in aged mice.
• Ala increased Wnt3a, phospho-CREB, and active β-catenin levels in aged colon organoids.
• Ala improved microbiome diversity, altered the bacterial composition, and modulated immune cell profiles in aged mice.

Conclusions:

• Alamandine (Ala) effectively reverses the 'leaky gut' phenotype associated with aging.
• Ala restores gut barrier function by modulating the gut-BM axis and improving microbiome homeostasis.
• Ala shows promise as a therapeutic agent for age-related gastrointestinal and immune dysfunctions.