The Latest Mitochondrially Targeted Antioxidant Research
Antioxidants that take the form of pills you buy at the store do nothing beneficial for you, and may even be gently harmful to your long term health. So says the greater weight of evidence, and so the craze for antioxidants begins to look like the present decade's salutary example of magical thinking at work - just because things happen in cell cultures when a given compound is introduced doesn't mean the same thing will happen when you eat that compound. A cell culture and your biochemistry are two very different things.
But wait, you might say, isn't oxidative stress of central importance in aging? All those oxidative, reactive compounds flying around the insides of cells damaging critical things - such as those produced by mitochondria, thought to be an important contribution to aging? Well, sure, but that still doesn't mean that eating things that happen to react in a given way with oxidants in a test tube will do any good.
The body and its cells are a vast city of many roads, a complex system that acts to steer all incoming chemicals into narrow, specific paths. The research of recent years suggests that ingested antioxidants from the store really don't do much because they will never end up face to face with the oxidative compounds that matter, or in the places that matter. This, at least, is the supposition because researchers have demonstrated ways to push antioxidants to where they do matter, and have extended life in mice by doing this. The place that matters is the mitochondria, source of oxidative compounds, and there are two approaches here: firstly, genetic engineering to increase the levels of natural antioxidants such as catalase in the mitochondria, and secondly to carefully construct chemicals that the body will delivery to the mitochondria even if they are ingested.
This latter approach is seeing more interest of late, and a number of different research groups are working on designing and testing mitochondrially targeted antioxidants in rodents. Here is the latest research report from the Russian group led by Vladimir Skulchev:
The effect of the mitochondria-targeted, plastoquinone-containing antioxidant SkQ1 on the lifespan of outbred mice and of three strains of inbred mice was studied. ... For comparison, we also studied mole-voles and dwarf hamsters, two wild species of small rodents kept under simulated natural conditions....
SkQ1 prevented age-dependent disappearance of estrous cycles of outbred mice, [while] male BALB/c mice had shorter lifespan than females, and SkQ1 increased their lifespan to the values of the females. In the females, SkQ1 retarded development of such trait of aging as heart mass increase. Male C57Bl/6 mice [lived] as long as females. SkQ1 increased the male lifespan, the longevity of the females being unchanged. SkQ1 did not change food intake by these mice. Dwarf hamsters and mole-voles kept in outdoor cages or under simulated natural conditions lived longer if treated with SkQ1.
The effect of SkQ1 on longevity of females is assumed to mainly be due to retardation of the age-linked decline of the immune system.
For those who are interested, one of the works in slow progress over at Open Cures is a protocol for the laboratory production of SkQ1:
The present protocol is based mainly on the supplementary material provided in a paper by (Antonenko et al, 2008) in which the authors successfully synthesized and used SkQ1 in animal experiments.
In general, the effects of mitochondrially targeted antioxidants of this type on longevity start to look as through they're in the same rough vicinity of everything else that manipulates mitochondrial operation or metabolism in mice - so rather than focusing on this as something to be chased, I think it makes more sense to see this research as a confirmation of the importance of mitochondria in aging. We should be forging ahead far more aggressively on the ways and means to repair mitochondrial damage or otherwise make it irrelevant.
While I don't disagree...isn't this something that can come to fruition sooner, as in the next few years? That's worthwhile, particularly for those of us without the willpower for caloric restriction. Another couple years of life is a gift worth treasuring, particularly if it is the bridge to actuarial escape velocity.
It's very important to note that SkQ1 has never been shown to extend the life of genetically normal, healthy, well-cared-for, non-toxin-administered animals of any species. All of the controls animals in these experiments were significantly (and in some cases miserably) short-lived for their species, and SkQ1 partly normalized those shortened life expectancies (and, as noted, in a couple of cases didn't even do this). The possible exception to this is the mole-vole, where there isn't enough historical experience to know how long a well-cared-for cohort of the species should live.
Relieving a sick mouse of the effects of a nasty environment or an abnormal genetic makeup may be suggestive of therapeutics for analogous human conditions, but it doesn't tell you anything about aging.
This is more likely to be a potential treatment for mitochondrial myopathies. Here, pathogenic over-the-roof ROS levels creates a vicious cycle for disease progression. As a see it, this could somehow decrease or stop disease progression. I am affected by this disease, so this could be just wishful thinking.