Magnesium Deficiency Accelerates Gut Aging and Increases Susceptibility to Colitis.

Magnesium levels decline with age specifically in the gut across species.

• An age-related decline in magnesium (Mg) levels was identified specifically in the gut across species.
• This age-associated reduction in gut Mg prompted investigation of its role in intestinal health.
• The decline was characterized as gut-specific rather than systemic.

Magnesium restriction accelerates gut aging in old mice but not in young mice.

• Functional studies demonstrated that Mg restriction accelerates gut aging selectively in old mice.
• Young mice did not show accelerated gut aging under Mg restriction, indicating an age-dependent vulnerability.
• These findings suggest that aging sensitizes the intestine to the effects of Mg deficiency.

Magnesium restriction aggravates colitis severity in mice.

• Dietary Mg deficiency was shown to aggravate colitis severity in mouse models.
• This effect was demonstrated through functional studies using Mg-restricted diets.
• The aggravation of colitis adds to the evidence that Mg deficiency has direct consequences for intestinal inflammation.

Dietary magnesium deficiency reshapes the phosphoproteome and N-glycoproteome, destabilizing adhesion complexes in mouse intestinal tissue.

• Multi-omics analysis of mouse tissues revealed that dietary Mg deficiency reshapes both the phosphoproteome and N-glycoproteome.
• These molecular changes resulted in destabilization of adhesion complexes.
• Destabilization of adhesion complexes is described as a hallmark of intestinal aging and inflammation.
• The findings link Mg deficiency to known molecular mechanisms of gut aging at the proteome level.

In the UK Biobank cohort, dietary magnesium intake was inversely correlated with the risk of gut disorders.

• The UK Biobank cohort analysis included n = 182,213 participants.
• Dietary Mg intake was inversely correlated with gut disorder risk.
• A dietary Mg intake range of 334.7–420.0 mg/day conferred significant protection against Crohn's disease, ulcerative colitis, irritable bowel syndrome, and diverticular disease.
• The association covered four distinct gut disorders, suggesting a broad protective effect of adequate Mg intake.

Magnesium supplementation is identified as a potential strategy to counteract age-related gut dysfunction.

• The findings identify Mg homeostasis as a key regulator of gut health.
• The authors highlight Mg supplementation as a potential strategy to counteract age-related gut dysfunction.
• This conclusion is supported by both the animal model data and the large-scale human cohort findings.