Abstract
Aging is linked to a higher incidence of gut diseases such as inflammatory bowel disease (IBD), yet the underlying mechanisms remain unclear. We identified an age-related decline in magnesium (Mg) levels specifically in the gut across species, prompting investigation of its role in intestinal health. Functional studies demonstrated that Mg restriction accelerates gut aging in old but not in young mice and aggravates colitis severity. Multi-omics analysis of mouse tissues revealed that dietary Mg deficiency reshapes the phosphoproteome and N-glycoproteome, destabilizing adhesion complexes, a hallmark of intestinal aging and inflammation. In the UK Biobank cohort (n = 182,213), dietary Mg intake was inversely correlated with gut disorder risk, with 334.7-420.0 mg/day conferring significant protection against Crohn’s disease, ulcerative colitis, irritable bowel syndrome, and diverticular disease. These findings identify Mg homeostasis as a key regulator of gut health and highlight Mg supplementation as a potential strategy to counteract age-related gut dysfunction.