Proc Natl Acad Sci U S A. 2008 Apr 7 [Epub ahead of print]
Magnesium deficiency accelerates cellular senescence in cultured human fibroblasts.
Killilea DW, Ames BN.
Nutrition and Metabolism Center, Children's Hospital Oakland Research Institute, Oakland, CA 94609.
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.
PMID: 18391207
http://www.pnas.org/cgi/content/abstract/0712401105v1
http://www.pnas.org/cgi/reprint/0712401105v1
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Study links magnesium deficiency to faster aging
Tue Apr 8, 11:26 PM ET
CHICAGO (AFP)
A lack of magnesium accelerates aging in human cells, which may explain the link between any long-term deficiency and a higher risk of aging-related diseases, according to a new study.
Magnesium is essential for hundreds of biochemical reactions in the body. It helps maintain normal muscle and nerve function, keeps heart rhythm steady, and keeps bones strong.
Yet research has shown that, at least in the United States, more than half the population is lacking in magnesium due to deficiencies in their diet, potentially increasing their risk of cardiovascular disease, hypertension, diabetes, osteoporosis and some cancers.
To try to understand why magnesium deficiency predisposes people to disease, Bruce Ames and researchers at Children's Hospital Oakland Research Institute in California studied the long-term effects of moderate magnesium deficiency on human fibroblasts, cells that provide a structural framework for many tissues in the body.
They cultured the cells for their entire lifespan, a period of three to four months, to mimic the effects of a lack of magnesium in the study which appeared Monday in the Proceedings of the National Academy of Sciences.
They found that while the cells survived and divided normally under moderate magnesium-depleted conditions, they appeared to become older quicker than cells grown in normal magnesium concentrations.
"Magnesium deficiency affects the way the cells age. Accelerated cellular aging affects the way tissue functions," said David Killilea, an associate staff scientist in the Nutrition and Metabolism Center at Children's Hospital Oakland Research Institute.
"We are now thinking that cellular consequences of magnesium deficiency may be driving long-term chronic disease."
Ames and Killilea suggested the markers of accelerated cellular aging in magnesium-deficient cells may indicate that the cells were in triage mode, saving resources for indispensable metabolic processes at the expense of long-term function.
As for diagnosing and treating chronic moderate magnesium deficiency, there is no good laboratory marker for this type of condition. It tends to fly under the radar, the scientists said.
"You could be moderately deficient for a long time and not know it," said Killilea.
Food sources rich in the micronutrient include green vegetables such as spinach, beans, nuts, and unrefined grains.