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An attempt to prevent senescence: A mitochondrial approach

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An attempt to prevent senescence: A mitochondrial approach Empty An attempt to prevent senescence: A mitochondrial approach

Post  CausticSymmetry on Tue Feb 10, 2009 5:24 pm

Biochim Biophys Acta. 2008 Dec 29.
An attempt to prevent senescence: A mitochondrial approach.
Skulachev VP, Anisimov VN, Antonenko YN, Bakeeva LE, Chernyak BV, Erichev VP, Filenko OF, Kalinina NI, Kapelko VI, Kolosova NG, Kopnin BP, Korshunova GA, Lichinitser MR, Obukhova LA, Pasyukova EG, Pisarenko OI, Roginsky VA, Ruuge EK, Senin II, Severina II, Skulachev MV, Spivak IM, Tashlitsky VN, Tkachuk VA, Vyssokikh MY, Yaguzhinsky LS, Zorov DB.

A. N. Belozersky Institute of Physico-Chemical Biology, Moscow State University, Vorobyevy Gory 1, 119991 Moscow, Russia; Faculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University, Vorobyevy Gory 1, 119991 Moscow, Russia.

Antioxidants specifically addressed to mitochondria have been studied to determine if they can decelerate senescence of organisms. For this purpose, a project has been established with participation of several research groups from Russia and some other countries. This paper summarizes the first results of the project. A new type of compounds (SkQs) comprising plastoquinone (an antioxidant moiety), a penetrating cation, and a decane or pentane linker has been synthesized. Using planar bilayer phospholipid membrane (BLM), we selected SkQ derivatives with the highest permeability, namely plastoquinonyl-decyl-triphenylphosphonium (SkQ1), plastoquinonyl-decyl-rhodamine 19 (SkQR1), and methylplastoquinonyldecyltriphenylphosphonium (SkQ3). Anti- and prooxidant properties of these substances and also of ubiquinonyl-decyl-triphenylphosphonium (MitoQ) were tested in aqueous solution, detergent micelles, liposomes, BLM, isolated mitochondria, and cell cultures. In mitochondria, micromolar cationic quinone derivatives were found to be prooxidants, but at lower (sub-micromolar) concentrations they displayed antioxidant activity that decreases in the series SkQ1=SkQR1>SkQ3>MitoQ. SkQ1 was reduced by mitochondrial respiratory chain, i.e. it is a rechargeable antioxidant. Nanomolar SkQ1 specifically prevented oxidation of mitochondrial cardiolipin. In cell cultures, SkQR1, a fluorescent SkQ derivative, stained only one type of organelles, namely mitochondria. Extremely low concentrations of SkQ1 or SkQR1 arrested H(2)O(2)-induced apoptosis in human fibroblasts and HeLa cells. Higher concentrations of SkQ are required to block necrosis initiated by reactive oxygen species (ROS). In the fungus Podospora anserina, the crustacean Ceriodaphnia affinis, Drosophila, and mice, SkQ1 prolonged lifespan, being especially effective at early and middle stages of aging. In mammals, the effect of SkQs on aging was accompanied by inhibition of development of such age-related diseases and traits as cataract, retinopathy, glaucoma, balding, canities, osteoporosis, involution of the thymus, hypothermia, torpor, peroxidation of lipids and proteins, etc. SkQ1 manifested a strong therapeutic action on some already pronounced retinopathies, in particular, congenital retinal dysplasia. With drops containing 250 nM SkQ1, vision was restored to 67 of 89 animals (dogs, cats, and horses) that became blind because of a retinopathy. Instillation of SkQ1-containing drops prevented the loss of sight in rabbits with experimental uveitis and restored vision to animals that had already become blind. A favorable effect of the same drops was also achieved in experimental glaucoma in rabbits. Moreover, the SkQ1 pretreatment of rats significantly decreased the H(2)O(2) or ischemia-induced arrhythmia of the isolated heart. SkQs strongly reduced the damaged area in myocardial infarction or stroke and prevented the death of animals from kidney ischemia. In p53(-/-) mice, 5 nmol/kgxday SkQ1 decreased the ROS level in the spleen and inhibited appearance of lymphomas to the same degree as million-fold higher concentration of conventional antioxidant NAC. Thus, SkQs look promising as potential tools for treatment of senescence and age-related diseases.
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An attempt to prevent senescence: A mitochondrial approach Empty Re: An attempt to prevent senescence: A mitochondrial approach

Post  Nuada on Tue Feb 10, 2009 10:34 pm

Forgive my ignorance but what is this SkQs that is mentioned in the article? And since hair loss is related to senescence, does this mean that skqs can do something about it?

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An attempt to prevent senescence: A mitochondrial approach Empty Re: An attempt to prevent senescence: A mitochondrial approach

Post  CausticSymmetry on Wed Feb 11, 2009 4:51 pm

Nuada - SkQ's are a very potent, synthesized antioxidant that combines a positively charged ion linked with petroleum based substance.

Think of this stuff as a "super" Ubiquinol (Active Co-Q10), but it would have to be proven safe for human use.
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An attempt to prevent senescence: A mitochondrial approach Empty Re: An attempt to prevent senescence: A mitochondrial approach

Post  MikeGore on Sun Sep 16, 2018 1:38 am

Hi,

I have recently heard a lot about SkQ1, and wondering what further thoughts you have about it? Is it currently available to buy and is it safe for human consumption? Also, is this thing natural?

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An attempt to prevent senescence: A mitochondrial approach Empty Re: An attempt to prevent senescence: A mitochondrial approach

Post  CausticSymmetry on Sun Sep 16, 2018 1:07 pm

MikeGore wrote:Hi,

I have recently heard a lot about SkQ1, and wondering what further thoughts you have about it? Is it currently available to buy and is it safe for human consumption? Also, is this thing natural?

From what I've heard it's a mixed experience so far.

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An attempt to prevent senescence: A mitochondrial approach Empty Re: An attempt to prevent senescence: A mitochondrial approach

Post  magic_gro on Fri Apr 12, 2019 3:54 pm

wouldn't methylene blue already be an awesome mitochondrial antioxidant way better than CoQ10?
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An attempt to prevent senescence: A mitochondrial approach Empty Re: An attempt to prevent senescence: A mitochondrial approach

Post  CausticSymmetry on Tue Apr 16, 2019 9:38 am

magic_gro wrote:wouldn't methylene blue already be an awesome mitochondrial antioxidant way better than CoQ10?

Methylene blue is something not to use casually for a few reasons. It's not a one size fits all treatment. Here are a few reasons aside from a wide number of side-effects I will not mention here.

Methylene blue due to its monoamine oxidase (MAO) inhibiting property may precipitate potentially fatal serotonin toxicity at doses >5mg/kg and rarely can cause severe anaphylactic shock.

Methylene blue is contraindicated in patients who have developed hypersensitivity reactions to it and in severe renal (kidney) insufficiency. It is relatively contraindicated in G6PD deficient patients as it can cause severe hemolysis and also in patients with Heinz body anemia.

Methylene blue is a MAO inhibitor and therefore can interact with selective serotonin reuptake inhibitor (SSRI) and MAO inhibitors to cause serious serotonin toxicity.

It also interacts with dapsone and forms hydroxylamine which oxidizes hemoglobin causing hemolysis.

Vitamin K2 possess higher antioxidant activity than Co-Q10 (on that note, quite a large number of things do). Lipoic acid will generate (or increase CoQ10 levels).

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An attempt to prevent senescence: A mitochondrial approach Empty Re: An attempt to prevent senescence: A mitochondrial approach

Post  Southbeach on Sat Apr 20, 2019 3:24 pm

CS- Out of curiousity, how do you think skQ's stack up against Nicotinamide Riboside ?

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An attempt to prevent senescence: A mitochondrial approach Empty Re: An attempt to prevent senescence: A mitochondrial approach

Post  CausticSymmetry Today at 2:57 pm

Southbeach wrote:CS- Out of curiousity, how do you think skQ's stack up against Nicotinamide Riboside ?  

No idea, would have to research it. But for what it's worth, I'm not too sold on NR being that more superior to regular niacin. At least for now, there's no evidence that it outperforms it enough to be worth the expense.


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