Magnesium Deficiency Accelerates Aging and Shortens Healthspan

The global population is undergoing an expanding epidemic of T2DM. Insulin resistance (IR) is at its center. IR is linked to many age-accelerating hormones and magnesium deficiency (MgD) is tightly linked to IR. Deficiencies of multiple vitamins, including A, B1-3,5,6,9,13, D, and E are tied to MgD, as Mg is linked to their activation. Optimal signaling of Mg dependent G-protein coupled receptors (GPCRs), the largest family of membrane proteins, extends healthspan. Indeed Mg is critical to most human metabolic functions. MgD increases the kynurenine to tryptophan (K/T) and the Ca:Mg ratios, both biomarkers for inflammaging, and has a strong connection to many cancers, cardiovascular disease (CVD), dementia, autoimmune/infectious disease, and obesity. Short chain fatty acids (SCFAs) are harbingers of optimal health and over 90% of them are produced by gut bacteria. However, these bacteria need Mg to produce butyrate, propionate, and acetate, as they do for secondary bile acids and indoles, known longevity agents. Mg also enables solar driven production of vitamin D3 in skin. Yet despite these associations between accelerated aging/healthspan and MgD, laboratory reference ranges for serum Mg (~0.75-0.95 mmoles/L) continue to overlook clinical MgD (migraines and premenstrual syndrome ~ 0.75-0.85 mmoles/L). Mg depleted soil and Western diets further exacerbate the epidemic, as does decreased absorption with age. The physiologic capacity of Mg is extensive and complex. Accordingly, this limited but focused narrative review attempts to link some of the deleterious effects of a long-term Mg shortfall with the premature symptoms of aging and a shortened healthspan.