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Micronutrients & Aging
First Time Evidence that Long-Term Magnesium Deficiency Causes Cellular Aging

"Magnesium deficiency in the United States is shockingly high, easily over the half the population, but at the same time it's an underappreciated public health problem."

In an April Procedures of the National Academy of Sciences publication, David Killilea, PhD, and Bruce Ames, PhD, of CHORI’s Center for Nutrition and Metabolism, report on the intriguing results of prolonged moderate magnesium deficiency on human fibroblast cells.

“We wanted to get a better understanding of the consequences of magnesium deficiency on the cell,” says Dr. Killilea.

While many studies have assessed the effects of micronutrient deficiency, this is one of the first to investigate the impact of magnesium deficiency in a more real-world model by studying moderate magnesium deficiency on human fibroblast cells over the entire lifespan of those cells.

"Most of the previous cellular and animal studies have only looked at the impact of extreme magnesium deficiency for a short period of time," says Dr. Killilea. "This isn't really reflective of what actually happens in human populations. Most of us have lower than optimal intake, but not none at all."

Unlike cells deprived of all magnesium, which undergo severe stress and die off within a week, the cells in the moderately magnesium deprived medium initially appeared to be relatively healthy and minimally impacted by the lack of magnesium. Further investigation provided some revealing results, however.

"We measured the number of times the cells double, or their replicative capacity, and found it was significantly less in magnesium deficient conditions," Dr. Killilea says.

Cell viability wasn't impacted at all, however, which suggested that the cause of the reduced replicating power could be related to cellular senescence, or aging.
"We looked at both bio-markers and protein expression related to cellular sene-scence, and in both cases, they were increased under mag-nesium deficient conditions. In other words, the cultures behaved as if they were older than they actually were."
That wasn't the only surprising aspect of the study, however. In addition to increased makers of cellular aging, there was an increase in the number of shortened telomeres. All chromosomes contain telomeres, extra portions of DNA at the end of our DNA strands, which provide a buffer during cell division.

"Every time the cell divides, it has to copy the DNA, but it never gets it perfectly right at the very end of the strand," explains Dr. Killilea. "We have several thousand extra base pairs at the end of every chromosome that get shortened every time the cell divides."

Over time, if those telomeres become too short, the aging process in the cells get activated, which is exactly what Dr. Killilea observed in the magnesium deficient cells.

"That fact that we found significantly shortened telomeres in the magnesium deprived cells indicates chronic stress that manifests itself in terms of health and viability in the long term."

Such a finding - the first time shortened telomeres has been associated with micronutrient deprivation - is consistent with the concept of metabolic triage, which
Dr. Ames has suggested as a long term consequence of nutrient deficiency in general. Dr. Killilea explains it this way:

"If you're a cell, and you only have 80 percent of a nutrient you need, you'll use that 80 percent for the most important processes you need to get through the day, but to do that, you have to shortchange some other process. While the cells can live with this if they have to, we think the long term consequence is increased cellular aging."

Understanding the underlying mechanism by which magnesium deficiency causes age acceleration requires further exploration. Drs. Killilea and Ames would like to determine what activates the aging process, and why and how magnesium is available for some processes and not others. Nevertheless, the new PNAS study provides significant evidence of the interrelationship between micronutrient deficiency and overall health.

"At least in cell culture lines, moderate but prolonged magnesium deficiency has a consequence," says Dr. Killilea. "The cell can survive, but the long term consequence is that the cell population is not as healthy at the end of its life span."

Whether this translates to the whole animal or human remains to be seen, but in the mean time, Drs. Killilea and Ames will continue to investigate the mechanisms that cause magnesium deprivation to accelerate aging, pursuing the long term goal of understanding what causes aging and aging-related diseases and how simple things like addressing micronutrient deficiency could turn aging-related health decline around.

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Tuesday, May 17, 2011 8:19 AM

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