{"id":195,"date":"2014-01-14T17:50:13","date_gmt":"2014-01-14T17:50:13","guid":{"rendered":"http:\/\/joshmitteldorf.peachpuff-wolverine-566518.hostingersite.com\/?p=195"},"modified":"2014-01-30T22:28:41","modified_gmt":"2014-01-30T22:28:41","slug":"mitoq-targeted-coq10","status":"publish","type":"post","link":"https:\/\/scienceblog.com\/joshmitteldorf\/2014\/01\/14\/mitoq-targeted-coq10\/","title":{"rendered":"MitoQ = Targeted CoQ10"},"content":{"rendered":"

CoQ10 plays a crucial role both in energy production and in detox. \u00a0Our bodies make less of it as we age, and we function less well for that. For more than 30 years, supplementation with CoQ10 has been identified as a promising anti-aging strategy and preventive for diseases of the heart and the brain. \u00a0But in extensive animal studies and dozens of clinical trials, CoQ10 has shown modest benefit, or none at all. \u00a0Part of the problem is that, when CoQ10 is taken into the digestive system, very little of it gets to the site where it can work. \u00a0Where CoQ10 belongs is in the cellular energy factories, the organelles called mitochondria. \u00a0Very recently, a mitochondria-targeted form of CoQ10 has become commercially available. \u00a0Preliminary experiments with MitoQ<\/a> in animals and humans are very promising.<\/em><\/p>\n

 <\/p>\n

How much is enough?<\/strong><\/p>\n

At the Second SENS conference in 2004, I sidled up to an expert whom I respected and asked, \u201cWhat\u2019s the optimal dose of CoQ10?\u201d \u00a0He laughed and asked, in reply, \u201cHow much can you afford?\u201d*<\/p>\n

Mitochondria are \u201corganelles\u201d, hundreds of them in every cell, that provide the energy that is used for everything from thinking to fleeing Sabre-tooth tigers. \u00a0We have less mitochondria as we age, and the mitochondria we do have function less efficiently. \u00a0This fact contribuetes to diverse aspects of aging. \u00a0The high-energy redox chemistry of the mitohondria is also the primary source of free radicals that cause oxidative damage associated with age.<\/p>\n

Another role played by mitochondria is that they are the designated hit-men when a cell outlives its usefulness, or becomes cancerous or diseased, or needs to be eliminated for any reason. \u00a0Apoptosis<\/a> is the process by which an individual cell is programmed to commit suicide for the sake of the larger organism, and the mitochondria orchestrate the killing, emitting the chemicals that do the dirty work. \u00a0In older animals (and people), apoptosis becomes over-active, and we lose perfectly good nerve and muscle cells to cell suicide.<\/p>\n

Coenzyme Q<\/a>, a.k.a. ubiquinone, is a small molecule, a key chemical component in the working of the mitochondria and also the first-line anti-oxidant that prevents the generation of free radicals in the course of energy generation. \u00a0As we age, each mitochondrion has less ubiquinone than it needs to function well. \u00a0Long-lived species have more CoQ<\/a>, pound for pound, than short-lived species. Hence CoQ has been recognized as an anti-aging compound for twenty years. \u00a0Today it is routinely prescribed by many cardiologists, because statin therapy depletes CoQ.\"\"<\/p>\n

But eating ubiquinone doesn\u2019t work very well. \u00a0It is poorly absorbed in the digestive tract (the molecular variant called ubiquinol is supposed to mitigate this problem), little of it makes it into the blood stream, less into the cells, and a pittance to the mitochondria where it is needed.<\/p>\n

This may be one reason CoQ supplementation has failed to live up to its potential. \u00a0A Spanish Study (2004<\/a>) found that CoQ could increase the mean and maximum life spans** of rats on a diet rich in polyunsaturates. \u00a0(Polyunsaturated fats are prone to oxidation.) \u00a0Doses were modest, equivalent to daily 50mg capsules for humans. \u00a0But this result was exceptional. \u00a0More typical are these studies (Ref<\/a> Ref<\/a> Ref<\/a> Ref<\/a>), which begin with great enthusiasm, but report no benefit for life span or mortality in mice and rats.<\/p>\n

 <\/p>\n

Provenance of Mito-targeted CoQ<\/strong><\/p>\n

In the 1990s, Michael Murphy and Robin Smith, two New Zealand biochemists, had an idea to get ubiquinone more efficiently into the cells\u2019 mitochondria – the only place where it is useful. \u00a0It happens that part of the mitochondria\u2019s electrochemical activity is to continuously pump protons out through their membranes. \u00a0Hence they maintain a negative electric potential relative to the rest of the cell. \u00a0Anything with a positive charge is drawn into the mitochondria, and if it\u2019s not a proton, it won\u2019t be pumped right back out again. \u00a0Murphy and Smith were inspired to create a molecule that combined ubiquinone at one end with a chemical tugboat at the other, a positive ion that is \u201cchelated\u201d, meaning that the positive charge is spread over a large number of atoms so that there is less tendency for it to simply pair up with a negative ion and be permanently neutralized. \u00a0The chemical \u201ctugboat\u201d, called TPP for tri-phenyl phosphonium, had been developed 25 years earlier in the Moscow State University lab of Vladimir Skulachev (Grinius et al, 1970<\/a>). \u00a0Connecting the tugboat to the ubiquinone is a simple carbon chain that prevents interference between the chemical properties of the two ends (Smith and Murhpy, 1999<\/a>) \u00a0\"\"<\/p>\n

The next step was to synthesize this molecule in the lab – a task requiring a lot of ingenuity and lab experience, but Smith was up to it. \u00a0Then came years of testing the substance, first in cell cultures, then in animals, with various applications. \u00a0Targeting worked amazingly well, with virtually all of the Mito-Q molecules finding their way to the mitochondria.<\/a> This means that very low doses can result in very high effectiveness.<\/p>\n

Skulachev, who had pioneered the early work on the right-hand part of the molecule, picked up this thread early on, and has sponsored much of the research that has demonstrated the rejuvenating potential of the molecule. \u00a0The molecular tugboat is known as a \u201cSkulachev ion\u201d, and a similar molecule*** to MitoQ has been dubbed “SkQ” and explored in Russian experiments.<\/p>\n

Last year, a New Zealand company<\/a> completed licensing requirements and created a manufacturing facility, and MitoQ is now available by order on the Internet for delivery worldwide. \u00a0The product was first announced at the A4M annual showcase meeting<\/a> in November. \u00a0A year earlier, Skulachev’s company<\/a> had begun to sell SkQ as eyedrops, available thus far only in Russia. \u00a0Skulachev’s group has long-term plans<\/a> to develop the product for other uses as well, and to obtain licensing in Europe and America.<\/p>\n

Some of the reason for enthusiasm about MitoQ is theoretical, and hence tentative. \u00a0We know that apoptosis is on a hair trigger as we get older, and not just diseased cells but many useful, healthy cells are eliminating themselves. \u00a0Apoptosis has been linked to muscle wasting (sarcopenia) [Ref<\/a>] and loss of neurons associated dementia [Ref<\/a>]. \u00a0It is found in cell cultures that MitoQ strongly inhibits apoptosis, not surprising since peroxides in the mitochondria are a signal that brings on apoptosis, and MitoQ eats peroxide for breakfast. \u00a0There are also theoretical reasons to believe MitoQ might be effective in curbing loss of insulin sensitivity [Ref<\/a>].<\/p>\n

 <\/p>\n

Evidence for effectiveness of MitoQ<\/strong><\/p>\n

But the most convincing evidence comes from studies in animals and humans. \u00a0Rats were demonstrated to be resistant to a variety of insults, from ischemia (oxygen deprivation) to toxins to carcinogens to high blood pressure, after administering MitoQ to rats in their drinking water. \u00a0In a novel experment in mice, MitoQ was shown to protect against insulin resistance. \u00a0All these studies were reviewed in a 2011 paper by Smith and Murphy<\/a>. \u00a0Historically, there is a strong correlation of life extension drugs and the ability to enhance stress resistance. \u00a0\u201cTogether these findings show that MitoQ is protective against pathological changes in a number of animal models of mitochondrial oxidative damage that are relevant to human diseases.\u201d<\/p>\n

A lot more animal research was performed in Russia***. \u00a0In a rat model of Alzheimer\u2019s disease, SkQ reversed neuronal damage<\/a> in a few weeks. SkQ fed to rodents led to more rapid healing of skin wounds<\/a>, especially in old age. \u00a0The same paper reports that, applied topically, SkQ was able to reverse scarring. \u00a0Most interesting, the Russian team reports small increases in the mean life span<\/a> of a variety of animals, including mice and fruitflies. \u00a0The authors claim without supporting data that there were dramatic life span increases of mice outside of standard (sterile) lab conditions, in which they were exposed to disease and infection. \u00a0In another paper by Skulachev (2007)<\/a> a large number of animal studies are summarized, with impressive benefits for a broad range of aging diseases, including kidney damage and macular degeneration. \u00a0Many of the original papers behind this work are available in English through Springer from the journal Biochemistry Moscow<\/a>.<\/p>\n

There is very limited data thus far in humans. \u00a0Safety and toxicity tests were concluded with a year-long trial at 80mg\/day. \u00a0In one study, MitoQ failed to improve the condition of advanced Parkinson\u2019s patients, and in a second study MitoQ showed significant benefit for protecting against liver damage from Hepatitis C. \u00a0Dr Skulachev reports that he personally has improved his vision using Sk-Q eye drops.<\/p>\n

 <\/p>\n

Caveat<\/strong><\/p>\n

All this study was carried out under direction of people who have an interest in the success of the compound. \u00a0You don\u2019t have to think that scientists are congenitally dishonest to believe it is a good idea to protect them from incentives that might subtly bias their thinking or reporting. \u00a0Science Magazine a few weeks ago reported on the failure of mouse studies<\/a> to translate into human benefit. \u00a0Studies conducted by drug companies are notorious.<\/p>\n

 <\/p>\n

A Subjective Bottom Line<\/strong><\/p>\n

I\u2019ve known Dr Skulachev as a friend and colleague for more than a decade. \u00a0I trust that his work is solid and honest. \u00a0I had known that he was planning a campaign to commercialize SkQ, beginning with eye drops that began selling last year in Western Russia. \u00a0I was surprised and delighted to see that MitoQ is available as a commercial product, 10 years before I had expected. \u00a0It\u2019s my belief that MitoQ is a promising new anti-aging strategy, and I\u2019m signed on to be an early adopter.<\/p>\n

 <\/p>\n

——————-<\/p>\n

* Long-term supplementation with high-dose CoQ10 is being studied<\/a> as a treatment for and Parkinson\u2019s disease and other neurological diseases of aging. \u00a0\u201cHigh\u201d is up to 3,600 mg\/day, though one study found no further increase in bioavailable CoQ above 2,400 mg. \u00a0The best price<\/a> I was able to find for CoQ on line worked out to about $4\/g, so 2,400 mg per day would cost over $3,500 \/yr.<\/p>\n

** For those who follow details of rodent studies, the survival curve of this one stands out. \u00a0Most interventions that extend life span work mostly to prevent early deaths (\u201csquaring the curve\u201d). \u00a0Often the mean life span is increased, but the max life span in the group benefits much less, or not at all. \u00a0In this study, there is no benefit at all until nearly half the rats have already died of old age. \u00a0Then the death rate for the remaining rats is much lower. \u00a0Max life span is extended 24%, even as average life span is extended only 11%.\"\"<\/p>\n

*** In the Russian work, Skulachev is using a variant of the Mito-Q molecule based on plastoquinone rather than ubiquinone. \u00a0Plastoquinone is the equivalent of ubiquinone in green plants, and Skulachev reports that there is a wider range of effective dosage<\/a> for plastoquinone compared to ubiquinone. \u00a0Scientists at MitoQ disagree that plastoquinone is better.<\/p>\n","protected":false},"excerpt":{"rendered":"

CoQ10 plays a crucial role both in energy production and in detox. \u00a0Our bodies make less of it as we age, and we function less well for that. For more than 30 years, supplementation with CoQ10 has been identified as a promising anti-aging strategy and preventive for diseases of the heart and the brain. \u00a0But … Read more<\/a><\/p>\n","protected":false},"author":65,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"jetpack_post_was_ever_published":false,"_jetpack_newsletter_access":"","_jetpack_dont_email_post_to_subs":false,"_jetpack_newsletter_tier_id":0,"_jetpack_memberships_contains_paywalled_content":false,"_jetpack_memberships_contains_paid_content":false,"footnotes":""},"categories":[1],"tags":[],"class_list":["post-195","post","type-post","status-publish","format-standard","hentry","category-uncategorized"],"yoast_head":"\nMitoQ = Targeted CoQ10 - Josh Mitteldorf<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/scienceblog.com\/joshmitteldorf\/2014\/01\/14\/mitoq-targeted-coq10\/\" \/>\n<meta property=\"og:locale\" content=\"en_US\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"MitoQ = Targeted CoQ10\" \/>\n<meta property=\"og:description\" content=\"CoQ10 plays a crucial role both in energy production and in detox. \u00a0Our bodies make less of it as we age, and we function less well for that. For more than 30 years, supplementation with CoQ10 has been identified as a promising anti-aging strategy and preventive for diseases of the heart and the brain. \u00a0But ... 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The surprising fact that our bodies are genetically programmed to age and to die offers an enormous opportunity for medical intervention. It may be that therapies to slow the progress of aging need not repair or regenerate anything, but only need to interfere with an existing program of self-destruction. Mitteldorf has taught a weekly yoga class for thirty years. He is an advocate for vigorous self care, including exercise, meditation and caloric restriction. After earning a PhD in astrophysicist, Mitteldorf moved to evolutionary biology as a primary field in 1996. He has taught at Harvard, Berkeley, Bryn Mawr, LaSalle and Temple University. He is presently affiliated with MIT as a visiting scholar. In private life, Mitteldorf is an advocate for election integrity as well as public health. He is an avid amateur musician, playing piano in chamber groups, French horn in community orchestras. His two daughters are among the first children adopted from China in the mid-1980s. Much to the surprise of evolutionary biologists, genetic experiments indicate that aging has been selected as an adaptation for its own sake. This poses a conundrum: the impact of aging on individual fitness is wholly negative, so aging must be regarded as a kind of evolutionary altruism. Unlike other forms of evolutionary altruism, aging offers benefits to the community that are weak, and not well focussed on near kin of the altruist. This makes the mechanism challenging to understand and to model. more at http:\\\/\\\/mathforum.org\\\/~josh\",\"sameAs\":[\"http:\\\/\\\/AgingAdvice.org\"],\"url\":\"https:\\\/\\\/scienceblog.com\\\/joshmitteldorf\\\/author\\\/joshmitteldorf\\\/\"}]}<\/script>\n<!-- \/ Yoast SEO Premium plugin. -->","yoast_head_json":{"title":"MitoQ = Targeted CoQ10 - Josh Mitteldorf","robots":{"index":"index","follow":"follow","max-snippet":"max-snippet:-1","max-image-preview":"max-image-preview:large","max-video-preview":"max-video-preview:-1"},"canonical":"https:\/\/scienceblog.com\/joshmitteldorf\/2014\/01\/14\/mitoq-targeted-coq10\/","og_locale":"en_US","og_type":"article","og_title":"MitoQ = Targeted CoQ10","og_description":"CoQ10 plays a crucial role both in energy production and in detox. \u00a0Our bodies make less of it as we age, and we function less well for that. For more than 30 years, supplementation with CoQ10 has been identified as a promising anti-aging strategy and preventive for diseases of the heart and the brain. \u00a0But ... 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The surprising fact that our bodies are genetically programmed to age and to die offers an enormous opportunity for medical intervention. It may be that therapies to slow the progress of aging need not repair or regenerate anything, but only need to interfere with an existing program of self-destruction. Mitteldorf has taught a weekly yoga class for thirty years. He is an advocate for vigorous self care, including exercise, meditation and caloric restriction. After earning a PhD in astrophysicist, Mitteldorf moved to evolutionary biology as a primary field in 1996. He has taught at Harvard, Berkeley, Bryn Mawr, LaSalle and Temple University. He is presently affiliated with MIT as a visiting scholar. In private life, Mitteldorf is an advocate for election integrity as well as public health. He is an avid amateur musician, playing piano in chamber groups, French horn in community orchestras. His two daughters are among the first children adopted from China in the mid-1980s. Much to the surprise of evolutionary biologists, genetic experiments indicate that aging has been selected as an adaptation for its own sake. This poses a conundrum: the impact of aging on individual fitness is wholly negative, so aging must be regarded as a kind of evolutionary altruism. Unlike other forms of evolutionary altruism, aging offers benefits to the community that are weak, and not well focussed on near kin of the altruist. This makes the mechanism challenging to understand and to model. more at http:\/\/mathforum.org\/~josh","sameAs":["http:\/\/AgingAdvice.org"],"url":"https:\/\/scienceblog.com\/joshmitteldorf\/author\/joshmitteldorf\/"}]}},"jetpack_featured_media_url":"","jetpack_shortlink":"https:\/\/wp.me\/pgtN8h-39","jetpack_sharing_enabled":true,"_links":{"self":[{"href":"https:\/\/scienceblog.com\/joshmitteldorf\/wp-json\/wp\/v2\/posts\/195","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/scienceblog.com\/joshmitteldorf\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/scienceblog.com\/joshmitteldorf\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/scienceblog.com\/joshmitteldorf\/wp-json\/wp\/v2\/users\/65"}],"replies":[{"embeddable":true,"href":"https:\/\/scienceblog.com\/joshmitteldorf\/wp-json\/wp\/v2\/comments?post=195"}],"version-history":[{"count":0,"href":"https:\/\/scienceblog.com\/joshmitteldorf\/wp-json\/wp\/v2\/posts\/195\/revisions"}],"wp:attachment":[{"href":"https:\/\/scienceblog.com\/joshmitteldorf\/wp-json\/wp\/v2\/media?parent=195"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/scienceblog.com\/joshmitteldorf\/wp-json\/wp\/v2\/categories?post=195"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/scienceblog.com\/joshmitteldorf\/wp-json\/wp\/v2\/tags?post=195"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}