Fight Aging!

You might recall the work of Skulachev's research group in producing an ingested antioxidant compound that targets the mitochondria and extends life span in mice. Similarly, mice genetically engineered to produce more naturally-occurring antioxidants in their mitochondria also live longer. By way of comparison, all other forms of antioxidant examined to date generally do nothing for life span, and may even harm your health and longevity.

The plausible explanation for the effects of mitochondrially targeted antioxidants rests on the mitochondrial free radical theory of aging. In short, your mitochondria are powerplants, thousands of them in each cell of your body. They convert food into the chemicals used to power cellular processes, but emit damaging free radicals as a byproduct. Some fraction of aging is caused by the chain of events that occur as mitochondria progressively damage themselves with their own emissions. Thus anything that can soak up these free radicals at the source, before they cause any harm, should lower the rate at which biochemical damage occurs, and extend life span.

Now let me direct your attention to Antipodean Pharmaceuticals, a New Zealand based research group working to develop an antioxidant targeted to mitochondria. Their compound, called MitoQ, appears similar to the SkQ1 developed by Skulachev:

Antipodean's lead compound MitoQ (mitoquinone) is a mitochondria-targeted antioxidant that selectively blocks mitochondrial oxidative damage and prevents cell death. ... MitoQ is being evaluated as an oral treatment for liver inflammation that leads to fibrosis and is associated with metabolic dysfunction. The company is also investigating topical indications that involve mitochondrial dysfunction, including dermatologic applications and retinal degeneration.

It goes without saying that the company has no public aim to work on aging. This is the standard state of affairs, even overseas. In the US, the FDA does not recognize aging as a medical condition, and so will not permit any potential therapy to come to market. Regulators in many other markets are similarly inclined. Thus promising technologies of this sort are sidelined into those areas in which regulators allow development to proceed at all.

Here is a recent paper from the Antipodean folk, which demonstrates that this type of chemical is safe in mice. This result should probably be taken as reassuring for Skulchev's development process as well, given the similarities.

The mitochondria-targeted quinone MitoQ protects mitochondria in animal studies of pathologies in vivo and is being developed as a therapy for humans. However, it is unclear whether the protective action of MitoQ is entirely due to its antioxidant properties, because long-term MitoQ administration may alter whole-body metabolism and gene expression. To address this point, we administered high levels of MitoQ orally to wild-type C57BL/6 mice for up to 28 weeks and investigated the effects on whole-body physiology, metabolism, and gene expression, finding no measurable deleterious effects. In addition, because antioxidants can act as pro-oxidants under certain conditions in vitro, we examined the effects of MitoQ administration on markers of oxidative damage. There were no changes in the expression of mitochondrial or antioxidant genes as assessed by DNA microarray analysis. There were also no increases in oxidative damage to mitochondrial protein, DNA, or cardiolipin, and the activities of mitochondrial enzymes were unchanged. Therefore, MitoQ does not act as a pro-oxidant in vivo.

These findings indicate that mitochondria-targeted antioxidants can be safely administered long-term to wild-type mice.

Which is good news for this line of research. It appears to work the way we think it works, and doesn't cause any apparent unwanted side effects.

Rodriguez-Cuenca S, Cochemé HM, Logan A, Abakumova I, Prime TA, Rose C, Vidal-Puig A, Smith AC, Rubinsztein DC, Fearnley IM, Jones BA, Pope S, Heales SJ, Lam BY, Neogi SG, McFarlane I, James AM, Smith RA, & Murphy MP (2009). Consequences of long-term oral administration of the mitochondria-targeted antioxidant MitoQ to wild-type mice. Free radical biology & medicine PMID: 19854266