Mitochondrially Targeted Plastoquinone Derivatives as Anti-Senescence Drugs

One of the many lines of longevity research I've watched over the past couple of years is the work of Vladimir Skulachev on chemicals that target mitochondria when ingested and work as antioxidants to soak up the free radicals that mitochondria produce in the course of their role as the cell's power plants. Preventing the damage that those mitochondrial free radicals would have caused has the effect of extending life - aging is nothing more than the accumulation of damage, after all.

Skulachev's laboratory has demonstrated a 30% healthy life extension in mice through this methodology, while US research groups have used the naturally produced antioxidant catalase and gene engineering to achieve much the same sort of end result: antioxidants localized to mitochondria, and extension of healthy life in mice.

Skulachev, I should note, is involved in the Russian initiative Science Against Aging, and will be presenting at the forthcoming 4th Strategies for Engineered Negligible Senescence conference. I should direct your attention to the abstract of his study, which gives more details on the chemicals used:

There are numerous indications that senescence program declines physiological functions by means of toxic reactive oxygen species (ROS) produced in mitochondria. Hence, one may hope that mitochondrial-targeted antioxidants might be inhibitors of the senescence program. To study such a possibility, a project has been established with participation of several research groups from Russia, Sweden and USA.

A new type of compounds (SkQs) composed of plastoquinone (an antioxidant moiety), a penetrating cation, and a decane or pentane linker has been synthesized. Using planar bilayer phospholipid membrane (BLM), we selected SkQ derivatives with the highest permeability, namely plastoquinonyl decyltriphenylphosphonium (SkQ1), plastoquinonyl decylrhodamine 19 (SkQR1), and methylplastoquinonyl decyltriphenylphosphonium (SkQ3).


In the fungus Podospora anserina, the crustacean Ceriodaphnia affinis, drosophila, and mice, SkQ1 prolonged lifespan, being especially effective at early and middle stages of aging. In mammals, the effect of SkQs on aging was accompanied by inhibition of development of such age-related diseases and traits as cataract, retinopathy, glaucoma, balding, canities, osteoporosis, involution of the thymus, anemia, disappearance of estrous cycles in females and libido in males, peroxidation of lipids and proteins, etc.

Give the biotech revolution another decade, and synthesizing this sort of stuff in your garage - and then running lifespan studies on flies or nematodes - will be an affordable and plausible project for participants in the open biotech movement.


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