7 replies to this topic

[mrkosh1]

Biochemistry (Mosc). 2012 Jul;77(7):689-706.
What is "phenoptosis" and how to fight it?

Skulachev VP.

Source

Lomonosov Moscow State University, Belozersky Institute of Physico-Chemical Biology and Faculty of Bioengineering and Bioinformatics, Moscow, 119991, Russia. skulach@genebee.msu.ru.

Abstract

Phenoptosis is the death of an organism programmed by its genome. Numerous examples of phenoptosis are described in prokaryotes, unicellular eukaryotes, and all kingdoms of multicellular eukaryotes (animals, plants, and fungi). There are very demonstrative cases of acute phenoptosis when actuation of a specific biochemical or behavioral program results in immediate death. Rapid (taking days) senescence of semelparous plants is described as phenoptosis controlled by already known genes and mediated by toxic phytohormones like abscisic acid. In soya, the death signal is transmitted from beans to leaves via xylem, inducing leaf fall and death of the plant. Mutations in two genes of Arabidopsis thaliana, required for the flowering and subsequent formation of seeds, prevent senescence, strongly prolonging the lifespan of this small semelparous grass that becomes a big bush with woody stem, and initiate substitution of vegetative for sexual reproduction. The death of pacific salmon immediately after spawning is surely programmed. In this case, numerous typical traits of aging, including amyloid plaques in the brain, appear on the time scale of days. There are some indications that slow aging of higher animals and humans is also programmed, being the final step of ontogenesis. It is assumed that stepwise decline of many physiological functions during such aging increases pressure of natural selection on organisms stimulating in this way biological evolution. As a working hypothesis, the biochemical mechanism of slow aging is proposed. It is assumed that mitochondria-generated reactive oxygen species (ROS) is a tool to stimulate apoptosis, an effect decreasing with age the cell number (cellularity) of organs and tissues. A group of SkQ-type substances composed of plastoquinone and a penetrating cation were synthesized to target an antioxidant into mitochondria and to prevent the age-linked rise of the mitochondrial ROS level. Such targeting is due to the fact that mitochondria are the only cellular organelles that are negatively charged compared to the cytosol. SkQs are shown to strongly decrease concentration of ROS in mitochondria, prolong lifespan of fungi, invertebrates, fish, and mammals, and retard appearance of numerous traits of aging. Clinical trials of SkQ1 (plastoquinonyl decyltriphenylphosphonium) have been successfully completed so that the Ministry of Health of the Russian Federation recommends drops of very dilute (0.25 µM) solution of this antioxidant as a medicine to treat the syndrome of dry eye, which was previously considered an incurable disease developing with age. These drops are already available in drugstores. Thus, SkQ1 is the first mitochondria-targeted drug employed in medical practice.

[Googoltarian]

Thats great news! I personally can't wait to get this compound to try it

[niner]

SkQ1 has a molecular weight of 538g/m. The solution they're selling is 0.25 micromolar, so that works out to 135mcg per liter. Since it's being sold as eye drops, you'd probably get a few hundredths of a liter, so you'd be getting only a couple micrograms of SkQ1. If other Russian antiaging compounds are any guide as to price, this will probably work out to tens of millions of dollars per gram. You could synthesize your own for less, even if you had to build a lab and hire a chemist. Or you could get a Chinese contract synthesis house to do it for not too much. Considering that C60-olive oil adducts probably act in a similar manner, and maybe a lot better, they might be a better choice for whole body use. That said, I'm glad to see this compound FINALLY see the light of day. Maybe they'll market a formulation meant for whole body use that won't be so expensive. It's not likely to be cheap, though.

[mitomutant]

SkQ1 has a molecular weight of 538g/m. The solution they're selling is 0.25 micromolar, so that works out to 135mcg per liter. Since it's being sold as eye drops, you'd probably get a few hundredths of a liter, so you'd be getting only a couple micrograms of SkQ1. If other Russian antiaging compounds are any guide as to price, this will probably work out to tens of millions of dollars per gram. You could synthesize your own for less, even if you had to build a lab and hire a chemist. Or you could get a Chinese contract synthesis house to do it for not too much. Considering that C60-olive oil adducts probably act in a similar manner, and maybe a lot better, they might be a better choice for whole body use. That said, I'm glad to see this compound FINALLY see the light of day. Maybe they'll market a formulation meant for whole body use that won't be so expensive. It's not likely to be cheap, though.

This is probably a stupid question, but it would be more stupid not to ask it.

The main sympton of the mitochondrial defect is a progressive paralysis of my extra-ocular muscles (hell, it is called CPEO phenotype for a reason). Do you think SkQ1 eye drops have any chance to reach the extra ocular muscles ? Even at this low concentration I think it can be beneficial for me. My rationale is the eye muscles are attached to the eye and, hence, eye drops might reach them.

[niner]

The main sympton of the mitochondrial defect is a progressive paralysis of my extra-ocular muscles (hell, it is called CPEO phenotype for a reason). Do you think SkQ1 eye drops have any chance to reach the extra ocular muscles ? Even at this low concentration I think it can be beneficial for me. My rationale is the eye muscles are attached to the eye and, hence, eye drops might reach them.

It might help some. I'd feel a lot better about it if the concentration were a little bit higher. The extra-ocular muscles are mostly outside the eye, so they'd probably be better dosed systemically, but as you say, they are connected to the eye, so there might be a little bit that gets in. Since you have a mitochondrial defect, it's probably worth a try. You could always dose more frequently.

[mrkosh1]

I feel that SKQ1 may be safer than C60's in olive oil. I am not at all saying that I think C60 is dangerous, but I have simply read a lot of studies that indicate SKQ1 is safe in appropriate doses. I will be looking forward to human trials of oral SKQ1.

[jroseland]

Is C60 also an antioxidant?

I feel that SKQ1 may be safer than C60's in olive oil. I am not at all saying that I think C60 is dangerous, but I have simply read a lot of studies that indicate SKQ1 is safe in appropriate doses. I will be looking forward to human trials of oral SKQ1.

 

[Nate-2004]

There's a whole section on C60, why bump this old thread?
 

I wonder what became of the SkQ1 thing? This is the first I've even heard of it.