Magnesium deficiency accelerates cellular senescence in cultured human fibroblasts.
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 beta-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 age-related disease.
Killilea
David W
DW
Nutrition and Metabolism Center, Children's Hospital Oakland Research Institute, Oakland, CA 94609, USA. dkillilea@chori.org
Ames
Bruce N
BN
D002460:Cell Line; D016922:Cellular Senescence; D050759:Cyclin-Dependent Kinase Inhibitor p21; D005347:Fibroblasts / Q000473:pathology*; D006801:Humans; D008275:Magnesium Deficiency; D010100:Oxygen; D016615:Telomere
C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D010100:Oxygen