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Setting the Stage for Prevention
CHORI Scientists Establish Methylene Blue Delays Mitochondrial Aging

"The results clearly showed that MB increases the lifespan of cells - they live both longer and healthier lives," Dr. Atamna explains.

In a recent FASEB Journal publication, CHORI scientists Hani Atamna, PhD, Bruce Ames, PhD and their colleagues in the Center for Nutrition & Metabolism report on the intriguing development that methylene blue (MB) extends the lifespan of human IMR90 fibroblasts in tissue culture, delaying cellular aging by boosting mitochondrial function.

“The results indicate that MB probably works on the basic mechanism of aging. Mitochondrial dysfunction is one of the key mechanisms of aging, and it seems that MB interacts and works with the mitochondria,” says Dr. Atamna.

MB has been used in humans for decades to treat a variety of ailments, and has a strong safety profile with very few side effects. This is the first study to investigate the potential for MB to delay aging by reducing mitochondrial dysfunction and oxidative stress. The results were overwhelmingly positive, with MB-treated fibroblasts showing an increase in population doublings (PDLs) greater than 20 compared with control fibroblast cells.

In addition to finding significantly increased PDLs, oxygen consumption and heme synthesis as a result of MB exposure, Dr. Atamna's study also provided evidence for a function model of MB interaction.

"What I'm proposing is that MB works as an electron sponge, working in harmony with cellular metabolism," says Dr. Atamna. "Instead of allowing the mitochondria to produce an oxidant, the MB sponge absorbs the electron before a free radical can be produced. It then safely delivers the electron to a different location, where the MB sponge then releases it."

The MB sponge effect provides an alternative to the traditional approach of reducing free radicals through antioxidants by entirely bypassing the very production of the oxidant in the first place.
"While it's true that antioxidants intercept free radicals, when the oxidants are broken about, a secondary radical is produced that can sometimes be just as dangerous. That is simply the nature of chemistry."
In addition, Dr. Atamna says that kind of interception is very tricky, and it's not very efficient either. Once the secondary radicals are released into the cell, picking them up again becomes like finding a needle in a haystack. The fact that MB increased cellular oxygen consumption by 37 to 70 percent speaks to just how efficient MB is in comparison. But reducing oxidative stress is just part of the overall effect of MB.

"The results are very encouraging. We'd like to be able to eventually target preventing physical and cognitive decline in aging, and to specifically focus on Alzheimer's disease (AD). One of the key aspects of AD is mitochondrial dysfunction, specifically, the very components on which MB works," Dr. Atamna says.

With its long safety history and FDA-approved status, Dr. Atamna hopes to design a straightforward study to test the effects of MB on both aging and in patients in the early stages of AD, with the goal of delaying AD decline by as much as 5 years. In the mean time Dr. Atamna is hard at work to set the stage for those kinds of clinical trials.
"What we're really trying to do here is understand the mechanisms of what is actually going on, what MB is doing in the mitochondria, what treatment means for the effect on the brain," Dr. Atamna says.

"You have a wide spectrum of aging, but if you look closely at the details of what's going on, maybe we can find a way to use it to prevent or delay the onset of age-related decline."

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Tuesday, May 17, 2011 8:19 AM

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