An Interview With Vladimir Skulachev

I recently noticed a two-part interview with researcher Vladimir Skulachev on a Russian language medical news site. Long-time readers will recognize the name in connection with work on plastoquinone-based mitochondrially targeted antioxidants: Skulachev's group produces the SkQ series of compounds that in recent years have been shown to generate benefits and extend life in mice. These are noteworthy for working though dietary intake, rather than requiring injection like the SS class of mitochondrially targeted antioxidants.

Mitochondrially targeted antioxidants are thought to work by soaking up a usefully large portion of the reactive oxygen species (ROS) produced by mitochondria in cells at their source, before they can cause harm to cellular structures - and especially before they can damage mitochondrial DNA. Progressively accumulated oxidative damage to mitochondrial DNA is widely considered to be an important contribution to degenerative aging, per the mitochondrial free radical theory of aging.

Like many Russian biogerontologists, Skulachev is on the programmed aging side of the fence, seeing aging as more of an evolved genetic program that causes damage rather than as a matter of accumulated damage that causes systems to change as they head down the path toward failure. This is far from a trivial difference, as it informs the strategies that researchers adopt in attempts to remove degenerative aging from the human condition - the wrong choice leads down an expensive and largely ineffective path. For my part, I think that the evidence points towards damage rather than programs.

As always I should note that automated translation of Russian has a way to go yet: we can put men on the moon and make stem cells dance to our tune, but moving a few verbs around remains beyond us. Thus the quoted materials below have been tidied up with guesswork and interpolation; errors are probably mine where they appear:

Can I live a few hundred years?

Interviewer: Is there a limit to growth? How long, in principle, a person can expect to live?

Skulachev: I think that there is no limit, and sooner or later people will come to practical immortality. Before, I was afraid to say so, because it sounded too provocative, but now, perhaps, it is already possible. The development of biology is such fantastic pace, after 100 years it will be completely realistic to talk of changing human nature ... This, of course, will never be immortality in its idealized form - when a person, for example, is beneath a falling concrete slab, we will not have a way to return him to his former state. But if we exclude such an absolute disaster, it is possible to assume the reality of a Methuselah-like near future, the life of a few centuries.

In principle we have not reached a point where people could die from wear and tear of the body. So far, I'm sure that people die because of orders received from the genome - for evolution it is enough to live and then give a place to others. This is a purely evolutionary mechanism, not necessary for modern man who has ceased to adapt to the environment and began to adapt the environment to his needs. How it will end and how dangerous this situation is - that is another question.

Interviewer: If everyone would live like Methuselah, does not have the resources ...

Skulachev: A typical error. In fact, there are a lot of resources and those resources are growing in proportion to human knowledge. But I would again like to emphasize that our goal is not immortality. We set ourselves a much simpler task: to transfer humans from the category of aging organisms into the category of non-aging organisms. Non-aging organisms exist in nature, both animal and plant. But perhaps the most striking example is the naked mole rat: they do not suffer from cancer, cardiovascular and infectious diseases, and their life expectancy is extremely high for small rodents - more than 30 years. So, the recent work of biochemists show that naked mole rats turn off a number of regulatory systems that are active in genetically close relative species. And it is very likely that as a result they have interrupted signals that trigger the mechanism of aging.

Abolish age

Last year, the Russian market launched a brand new ophthalmic drug based on SkQ1 for the treatment of dry eye syndrome - an old man's disease is considered incurable. Droplets containing SkQ1 as active ingredient, resulted in the disappearance of disease symptoms in 60% of patients after three weeks of treatment. Now research is ongoing in eight clinics in Russia and two in Ukraine. There is reason to think that the positive effect of a more prolonged use SkQ1 can be even greater.

It can treat some cancers, we have found in animal experiments. But no evidence of carcinogenicity caused by SkQ has been received. There are two aspects to this result. First, the very low therapeutic concentrations of SkQ - thanks to the targeted effect the substance is effective in minute doses. And the second - it quickly breaks down in the body.

Now begins the process of registering our medicines in the United States. Because the clinical trials that need to be carried out in America are very expensive we started with the orphan disease of uveitis. This will reduce the number of participants and therefore costs. Uveitis is an extremely unpleasant condition in which the tissues of the eye are being targeted by the patient's own immune system. It is treated by large doses of steroid hormones with very serious adverse consequences. Now three independent labs in Minneapolis, Andover and Sunny Vale (USA) have already confirmed our experiments previously carried out on animals in Russia.

We have already completed clinical trials on glaucoma and cataracts, which took place in Russia. The results are being published. In the near future are going to get the permission of Ministry of Health to study SkQ1 for the treatment of macular degeneration. It is hoped to complete this process in the winter of this year. It should be noted that initially the Ministry met our project with great skepticism. Too unusual results ... But, fortunately, we are guided by the principles of evidence-based medicine, and can always explain how and why our product works.

So all in all it looks like we'll be seeing the use of mitochondrially targeted antioxidants to treat numerous conditions over the next decade. Given that the substances are going through clinical trials, it seems unlikely that they'll be easily available - regulated and controlled as drugs, with harsh penalties for anyone using them outside the system. Still, broader usage can only result in it becoming easier for DIYbio and home chemistry amateurs to synthesize their own supplies should they feel so inclined, and should the evidence warrant making the effort versus just giving the funds to the SENS Research Foundation instead.

Comments

There is an english language project website at http://en.skq-project.ru.
It sounds quite promising.

Posted by: Ralf at July 9th, 2013 6:55 AM

In principle we have not reached a point where people could die from wear and tear of the body. So far, I'm sure that people die because of orders received from the genome

Could anyone explain that please?

Posted by: nickdino at July 12th, 2013 3:22 AM

@nickdino: I believe his view is that genetic programs are the primary limiting factor on longevity, and if removed or suppressed then forms of stochastic damage such as random mutation to nuclear and mitochondrial DNA would then be a further limiting factor.

Posted by: Reason at July 12th, 2013 5:09 AM

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