An eminent Russian biochemist has been working fifteen years to get the cell’s most active anti-oxidant into the mitochondria, which is the locus of its action. Called “SkQ” for short, his designer drug administered in food, has been shown to make mice live longer; and topically it can induce regression of eye diseases in rodents, dogs and horses. While the long process of US FDA review has just begun, an eye drop containing SkQ has been approved for sale in Russia, and can now be purchased in Moscow drug stores.
Biochemical background: Ubiquinol in Mitochondria

Mitochondria are “organelles”, hundreds of independent energy factories floating within the cells of all higher life forms. Sugar is “burned” in the mitochondria, and the energy generated is stashed as molecules of ATP, which act like a battery that the rest of the cell can use. Muscle and nerve cells are large consumers of energy, and their function can be limited when mitochondria in aging cells begin to wane. Mitochondria have another role as well: they serve as executioners for diseased or damaged cells. It is the mitochondria that emit peroxides, which trigger a cascade of signals, culminating in cell suicide, or apoptosis. (This story is told colorfully and creatively in a book I highly recommend, called Power, Sex and Suicide by Nick Lane.)

Ubiquinone was named as the enzyme that is “found everywhere”. Every cell needs energy, and every cell relies on mitochondria to supply that energy, and every mitochondrion uses ubiquinone, both to create the energetic molecules of ATP that are exported for use in the cell’s primary functions, and also to clean up the mitochondria’s effluent of peroxides. Peroxides are an example of reactive oxygen species (ROS). ROS are toxic waste that corrodes the body’s delicate chemistry. At higher concentrations, peroxides constitute also a distress signal which can trigger cell suicide and even export a suicide message to neighboring cells.

As we age, we have less ubiquinone and there are dire consequences: less energy in our muscles and nerves; more toxic waste that damages and poisons more delicate chemicals; and over-active cell suicide that destroys healthy cells in our muscles and brains. We lose strength, sensitivity and mental acuity. Ubiquinone is sold as CoQ10, a nutritional supplement that some people take for heart health and oft-imputed anti-aging benefits. But no animal study has ever succeeded in extending life span with CoQ10. Perhaps its value is limited by bioavailability. Only a small portion of ingested CoQ10 makes its way from the stomach into the bloodstream, and a much tinier portion actually reaches the mitochondria where it is needed. This is the issue that Skulachev has addressed in such an innovative way with his molecule, which his friends and students have affectionately dubbed SkQ.

 

The molecule and how it works

Skuklachev’s molecule is designed like a tugboat pulling a barge on a chain. The barge on the left is a molecule like ubiquinone. The 10-carbon chain is a simple hydrocarbon. And the tugboat on the right consists of a positively charged phosphorus atom, surrounded by ligand residues that delocalize and shield the charge. This works because mitochondria, in nature’s design, are the only parts of a cell to carry a consistent electrical charge. They are continuously pumping protons out through their membranes, maintaining a negative electrical potential within the mitochondria.

SkQ-structure

The electrostatic attraction is a powerful lure, drawing the positively-charged tugboat into the mitochondria, and dragging the barge in behind. The effect is to concentrate SkQ a million-fold inside, compared to outside the mitochondria. This means that very tiny amounts can be effective antioxidants. SkQ is a very practical drug, inexpensive and non-toxic because it is administered in tiny doses.

Curiously, the “barge” on the left is not the version of CoQ that is used by mammals, but the plant version, called plastoquinone, which is an even more effective anti-oxidant. After comparing plastoquinone to ubiquinone in animal experiments, Skulachev switched to plastoquinone several years ago.

 

Anti-oxidant or signal molecule?

Readers of this column must be aware that I have been skeptical about anti-oxidants for life extension. It appears that SkQ may be an exception because it is so precisely targeted to mitochondria. There is some precedent for the exception, in that genetic interventions that are targeted to the mitochondria have also been found to extend life span in mice. This study arranges for extra copies of the anti-oxidant called catalase in the mitochondria only. Perhaps the reason for the exception is that to the mitochondria, peroxides not only cause molecular damage, but also can signal cell suicide. This is the theory that Skulachev has promoted.

He should know. In earlier days, Skulachev was responsible for elucidating the electrochemistry of mitochondria in relation to energy generation and programmed cell death.

 

Life extension in animals

Since 2007, Skulachev’s lab at Moscow State University has been publishing studies which demonstrate life extension, first in flies and other invertebrates then in a variety of different rodents. SkQ has also been shown to delay all the common diseases of aging in rats. The effect on life span is easily discerned, and is large under some circumstances:

SkQ-life-extension

Administered as eye drops, the effect has been more dramatic. Rabbits have been cured of glaucoma. Macular degeneration has regressed in horses and dogs.  Experimenting on himself, Skulachev reports that his age-related presbyopia has regressed to the point where he can see without glasses for the first time in many years.

 

Present and future

SkQ has cleared the Russian equivalent of FDA approval. Clinical trials have begun for SkQ, and preliminary results indicate that 80% of people who were given the drops for cataracts experience an improvement in visual acuity within half a year (unpublished).  As of last summer, SkQ eye drops have become available for sale in Moscow and environs through a partnership with a company named Mitotech, under the brand name Bизомитин, or Visomitin in a more familiar script.  Sales are brisk because Skuklachev is something of a legend in his own country. There is no present timetable for marketing Visomitin in America.