Magnesium deficiency accelerates cellular senescence in cultured human fibroblasts

Abstract

Magnesium inadequacy affects more than half of the U.S. population and is associated with increased risk for many age-related diseases, yet the underlying mechanisms are unknown. Altered cellular physiology has been demonstrated after acute exposure to severe magnesium deficiency, but few reports have addressed the consequences of long-term exposure to moderate magnesium deficiency in human cells. Therefore, IMR-90 human fibroblasts were continuously cultured in magnesium-deficient conditions to determine the long-term effects on the cells. These fibroblasts did not demonstrate differences in cellular viability or plating efficiency but did exhibit a decreased replicative lifespan in populations cultured in magnesium-deficient compared with standard media conditions, both at ambient (20% O 2) and physiological (5% O 2) oxygen tension. The growth rates for immortalized IMR-90 fibroblasts were not affected under the same conditions. IMR-90 fibroblast populations cultured in magnesium-deficient conditions had increased senescence-associated ␤-galactosidase activity and increased p16 INK4a and p21 WAF1 protein expression compared with cultures from standard media conditions. Telomere attrition was also accelerated in cell populations from magnesium-deficient cultures. Thus, the long-term consequence of inadequate magnesium availability in human fibroblast cultures was accelerated cellular senescence, which may be a mechanism through which chronic magnesium inadequacy could promote or exacerbate agerelated disease.oxygen tension ͉ telomeres ͉ tumor suppressor M agnesium is an essential micronutrient required for an extensive range of metabolic, regulatory, and structural activities. It is predominantly obtained from diet by eating green leafy vegetables and unprocessed grains (1). The typical U.S. diet has drifted away from these food sources in favor of more refined and often nutrient-poor food options, thus magnesium inadequacy has become quite common (2). Intake estimates generated by national surveys including the National Health and Nutrition Examination Survey (NHANES) have predominantly indicated that more than half of the U.S. population has magnesium intakes below the Estimated Average Requirement (EAR), a measure of population adequacy that is 2 SD below the Recommended Daily Allowance (3). Moreover, the incidence and severity of magnesium inadequacy is even greater in at-risk groups, including children, the poor, and the elderly (4, 5).Despite growing appreciation of the prevalence of magnesium inadequacy, essentially no immediate clinical symptoms are known, due in part to the lack of robust biomarkers of magnesium status in vivo. However, there is a sizeable literature on the functional consequences linked with long-term magnesium inadequacy. Epidemiological data have associated increased risk of several agingrelated diseases with chronic magnesium inadequacy, including cardiovascular disease, hypertension, diabetes, osteoporosis, and some cancers (1, 6-8). Numerous animal studies on magnesium inadequacy...

Impact of inorganic nutrients on maintenance of genomic stability

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