5 replies to this topic

[ta5]

The study is from October but the "medline" date is today for some reason. The full study is available. It was actually posted before.


Aging (Albany NY). 2012 Oct;4(10):686-94.

The mitochondria-targeted antioxidant SkQ1 but not N-acetylcysteine reverses aging-related biomarkers in rats.

Kolosova NG, Stefanova NA, Muraleva NA, Skulachev VP.
Institute of Cytology and Genetics SB RAS, Novosibirsk, Russia.

Although antioxidants have been repeatedly tested in animal models and clinical studies, there is no evidence that antioxidants reduce already developed age-related decline. Recently we demonstrated that mitochondria targeted antioxidant 10-(6'-plastoquinonyl) decyltriphenylphosphonium (SkQ1) delayed some manifestations of aging.Here we compared effects of SkQ1 and N-acetyl-L-cysteine (NAC) on age-dependent decline in blood levels of leukocytes,growth hormone (GH), insulin-like growth factor-1 (IGF-1), testosterone, dehydroepiandrosterone (DHEA) in Wistar and senescence-accelerated OXYS rats. When started late in life, supplementation with SkQ1 not only prevented age-related decline but also significantly reversed it. With NAC, all the observed effects were of the lower magnitude compared with SkQ1 (in spite of that dose of NAC was 16000 times higher). We suggest that supplementation with low doses of SkQ1 is a promising intervention to achieve a healthy ageing.
PMID: 23104863



"Starting from the age of 19 months OXYS and Wistar rats were randomly assigned to three groups (n = 17–24): control diet, diet supplemented with 250 nmol SkQ1 (synthesized as described earlier) or 650 mg NAC (MP Biomedicals, LLC, France) per kg of body weight per day."

[Elus]

I like their approach. A mitochondria-targeted antioxidant would be more effective than one that isn't targeted. The huge disparity in concentration of their respective reagents (targeted and untargeted) is good evidence that mitochondrial targeting works better. The reason for this might be that mitochondria are constantly generating reactive oxygen species (ROS, more commonly known as free radicals) by accidental electron leakage across the electron transport chain during OXPHOS (The cell's main ATP generating mechanism, which is located within mitochondria). There might be two reasons why mitochondrial targeting is effective.

#1. The mitochondria produce a high concentration of ROS, and thereby an antioxidant localized to that area would absorb greater quantities of ROS than an antioxidant that is free to wander other parts of the cell, and would thereby prevent those ROS from escaping to other parts of the cell where they could cause havoc.

#2. The mitochondrial genome is in close to a high concentration of ROS generated by the electron transport chain. Damage to this mitochondrial genome might cause all sorts of trouble to the cell, for instance by impairing energy metabolism. An antioxidant that could nullify ROS before they have a chance to interact with mitochondrial DNA might prevent downstream consequences of mtDNA damage.

That said...

An antioxidant is an absorber of ROS that would otherwise react with cellular components. The putative mechanism by which an antioxidant could slow aging is clear: by serving as a shield against ROS, antioxidants slow the accumulation of ROS-damage to vital cellular components.

However, it is less clear how an antioxidant could go beyond slowing damage to actually reversing it, as this sentence implies: "supplementation with SkQ1 not only prevented age-related decline but also significantly reversed it."

How does an antioxidant reverse damage?

My hypothesis would be that an antioxidant could lead to reversal of damage indirectly. What if antioxidants lessen oxidative burden and thereby allow the body's inherent repair mechanisms to catch up to the damage? In an alternative scenario where the antioxidant is not present, the repair mechanisms in the cell would be continually dealing with ROS-induced damage, and so ROS would eventually overwhelm the capacity of the the repair mechanisms to repair that damage.

I wonder if there are ways we could artificially boost cellular repair mechanisms. I suppose SENS is an indirect way of doing this. However, I agree with Aubrey de Grey when he says that tampering with metabolic processes and repair mechanisms is much more complicated than simply cleaning up damage that occurs as a result of those processes.

Edited by Elus, 03 May 2013 - 11:18 PM.

[jroseland]

That's a well articulated explanation, I think I'm going to quote it in an article

There might be two reasons why mitochondrial targeting is effective.

#1. The mitochondria produce a high concentration of ROS, and thereby an antioxidant localized to that area would absorb greater quantities of ROS than an antioxidant that is free to wander other parts of the cell, and would thereby prevent those ROS from escaping to other parts of the cell where they could cause havoc.

#2. The mitochondrial genome is in close to a high concentration of ROS generated by the electron transport chain. Damage to this mitochondrial genome might cause all sorts of trouble to the cell, for instance by impairing energy metabolism. An antioxidant that could nullify ROS before they have a chance to interact with mitochondrial DNA might prevent downstream consequences of mtDNA damage.

[Nate-2004]

Hmm, no SkQ1 available yet on Amazon lol.    I wonder how it is synthesized or extracted.

 

EDIT: Nevermind I just saw this thread was from 2013, jeez. What's with old threads being bumped 

Edited by Nate-2004, 16 February 2018 - 07:21 PM.

[Kentavr]

Hmm, no SkQ1 available yet on Amazon lol.    I wonder how it is synthesized or extracted.

 

EDIT: Nevermind I just saw this thread was from 2013, jeez. What's with old threads being bumped 

 

I suspect that plastoquinone is isolated from the leaves + and the reaction is carried out with triphenylphosphonium ion. The second stage is cleaned. All)

Edited by Kentavr, 17 March 2018 - 07:19 PM.

[Nate-2004]

Leaves?

 

I got some SkQ1 bromide from Mitolab but I've no idea if it's legit, 5 drops under the tongue each day.