January 06, 2009
Clioquinol Slows Brain Aging?
Clioquinol might help against a few neurodegenerative diseases by slowing aging.
Recent animal studies have shown that clioquinol – an 80-year old drug once used to treat diarrhea and other gastrointestinal disorders – can reverse the progression of Alzheimer's, Parkinson's and Huntington's diseases. Scientists, however, had a variety of theories to attempt to explain how a single compound could have such similar effects on three unrelated neurodegenerative disorders.
Researchers at McGill University have discovered a dramatic possible new answer: According to Dr. Siegfried Hekimi and colleagues at McGill's Department of Biology, clioquinol acts directly on a protein called CLK-1, often informally called "clock-1," and might slow down the aging process. The advance online edition of their study was published in Oct. 2008 in the Journal of Biological Chemistry.
"Clioquinol is a very powerful inhibitor of clock-1," explained Hekimi, McGill's Strathcona Chair of Zoology and Robert Archibald & Catherine Louise Campbell Chair in Developmental Biology. "Because clock-1 affects longevity in invertebrates and mice, and because we're talking about three age-dependent neurodegenerative diseases, we hypothesize that clioquinol affects them by slowing down the rate of aging."
Does clioquinol get inhibited by calorie restriction?
I do not recommend you start taking this drug. Clioquinol varies between species of animals and even between dog breeds. It might cause neurotoxicity by chelating metals. But at lower doses that same chelation might be beneficial for some. It might be the cause of subacute myelo-optico-neuropathy (SMON) in 10,000 people in Japan. A recent Cochrane review of the use of clioquinol against Alzheimer's Disease does not find that studies to date show a clear benefit.
Let the researchers mess with this one. If you want to slow your brain aging there are lots of lower risk ways to do that with more certain benefits. Start with more fruits, vegetables, and fish. Then spice it up with turmeric for the curcumin.
The circumstantial experimental evidence seems to suggest that Clioquinol's metal chelation is responsible according to the paper's abstract:
'The Anti-neurodegeneration Drug Clioquinol Inhibits the Aging-associated Protein CLK-1'
- J. Biol. Chem., Vol. 284, Issue 1, 314-323, January 2, 2009
"an inhibition that can be blocked by iron or cobalt cations, suggesting that chelation is involved in the mechanism of action of clioquinol on CLK-1."
If this is true, then possibly the neuroprotective effects of berry polyphenols and curcumin are due to their metal chelating properties, reducing excess metal absorption. BTW, green tea and rosemary extract inhibit iron uptake also.
'Green tea or rosemary extract added to foods reduces nonheme-iron absorption'
Phytic acid (IP-6, inositol hexaphosphate) is also a potent metal chelator found in grains and (esp. black sesame) seeds. It appears to be bioavailable and crosses the blood-brain barrier in lab animals. In vitro, it appears to protect neurons from cell death. See:
'Neuroprotective effect of the natural iron chelator, phytic acid in a cell
culture model of Parkinson’s disease' - Toxicology 245 (2008) 101–108
Of course, besides outright toxicity, these approaches could cause deficiencies.
I am curious whether phytic acid also inhibits CLK-1 expression.
Also, I only found one paper claiming that the phosphorus in phytic acid is not bioavailable, but given that excess phosphorus is associated with vascular/soft tissue calcification and other problems, I'd like to see some persuasive safety data.
As a final note, there are claims that idebenone (a synthetic ubiquinone) and methamphetamines are CLK-1 activators.
You confirm my reaction: If we only knew more about the optimal and current levels of various minerals we could use chelators and supplements to fine-tune to minimize damage and optimize benefits. At this point all the chelators seem too much like shooting in the dark.
turmeric helped my arthritis better than the prescripion nsaids. just thought i'd add that.
Very interesting that clioquinol has been used to treat intestinal disorders and is a potent anti-fungus--both of which are central to my hypothesis on Alzheimer's (see article on my site: "Does Alzheimer's Take Guts?")