The Science of Aging Gracefully:  Mitochondrial Targeted Antioxidants (MTAs)

The Science of Aging Gracefully: Mitochondrial Targeted Antioxidants (MTAs)

In 1954,  Denham Harman proposed the Free Radical Theory Of Aging (FRTA).  Harman suggested that extended exposure to reactive oxygen species (ROS, aka free radicals)  damaged cells and cellular functions over time and was the primary cause of aging and age-related chronic disease.

The average human body contains 100,000 trillion mitochondria, each one using oxygen and glucose to make and store the energy we need.   The energy conversion process is not perfect. About 2% of the oxygen consumed ends up as reactive oxygen species (ROS), about 20 grams per person per day.

Oxidative stress happens whoever there is imbalance between pro-oxidants (ROS) and anti-oxidants.  To stay in balance we need to find antioxidants that can neutralize 20 grams of ROS every day.

Peer reviewed literature during the past several years has attributed the etiology (source or cause) of virtually all chronic diseases to oxidative stress and the associated mitochondrial dysfunction that follows.

Location, Location, Location

Here is a simple pic of a cell.

 

The average human cell has between zero and 100s of thousands of mitochondria depending on cell type. 

ROS is the equivalent of a chemical fire. Like any fire, you want to fight it at the source before it damages the mitochondrion (mitochondrial dysfunction),  the nucleus/dna and the other organelles inside the cell walls. 

Evolutionary forces favored mutations that had more powerful MTAs kicking off the carotenoid family of antioxidants.  It took 1.8B years for single cell lifeforms to figure out how to neutralize ROS and harness the mitochondria power plant. 

The scientific community has just recently recognized the role MTAs play in chronic disease and aging. New MTA compounds are being developed including  MITOQ and Tiron.

MITOQ

One of the enzymes involved in the energy production cycle is ubiquinone commonly known as CQ-10. CQ-10 is sold and promoted as a MTA nutraceutical.

To improve bioavailability,  scientists have engineered a variant of CQ-10 that uses a form of salt that enables the combined molecule to enter and accumulate within the mitochondria.  MitoQ has been shown by numerous investigators(1) to help with age related diseases including colitis, Parkinson's and liver damage.

Tiron

Tiron is a non toxic iron based compound that can penetrate and accumulate within the mitochondria plasma membrane. It has been shown to have antioxidant properties. Fang et. al. (2) showed promise against UV induced oxidative stress in skin tissue.

Di-esterified 3S, 3’S astaxanthin

Fortunately, nature invented the most powerful MTA 700M years ago.  Animals such as copepods, krill and shrimp all produce this form of astaxanthin. Astaxanthin is much more powerful than MitoQ, in fact we would argue that astaxanthin protects CQ-10 from being oxidized by ROS so that it can participate in the energy production cycle.

Humans naturally make CQ-10 but don’t have the chemistry kit to make astaxanthin.  We evolved to get astaxanthin from our diet. Astaxanthin is so powerful that <12 milligrams of this MTA neutralizes the 20 grams of ROS that we make every day.  We used to get this dose by eating a chicken egg, some fish, shell fish or the offals of wild game. When we centralized animal production, we removed astaxanthin from the diet of our animals and in turn our diet.

M. Sztretye et. al. (3) in their article  “Astaxanthin: a Potential Mitochondrial-Targeted Antioxidant Treatment in Diseases and with Aging” observe that “astaxanthin is one of the most powerful natural compounds with remarkable antioxidant activity. "

We didn’t invent di-esterified 3S, 3’S astaxanthin,  nature did that work for us. We invented a way to extract natural astaxanthin from algae and combined the right compound with a delivery system that gets this powerful antioxidant into the right place, i.e. the mitochondria cell plasma membrane.

Adjuvia Astaxanthin,  natures most powerful Mitochondria Targeted Antioxidant.

1) Gioscia-Ryan, R. A., LaRocca, T. J., Sindler, A. L., Zigler, M. C., Murphy, M. P., and Seals, D. R. (2014) Mitochondria-targeted antioxidant (MitoQ) ameliorates age-related arterial endothelial dysfunction in mice. J. Physiol. 592, 2549–2561

Snow, B. J., Rolfe, F. L., Lockhart,M.M., Frampton, C.M., O’Sullivan, J. D., Fung, V., Smith, R. A., Murphy, M. P., and Taylor, K. M.; Protect Study Group. (2010) A double-blind, placebo-controlled study to assess the mitochondria-targeted antioxidant MitoQ as a disease modifying therapy in Parkinson’s disease. Mov. Disord. 25, 1670–1674

Oyewole, A. O., Wilmot, M.-C., Fowler, M., and Birch-Machin, M. A. (2014) Comparing the effects of mitochondrial targeted and localized antioxidants with cellular antioxidants in human skin cells exposed to UVA and hydrogen peroxide. FASEB J. 28, 485–494

         Dashdorj, A., Jyothi, K. R., Lim, S., Jo, A., Nguyen, M. N., Ha, J., Yoon, K.-   S., Kim, H. J., Park, J.-H., Murphy, M. P., and Kim, S. S. (2013) Mitochondria-targeted antioxidantMitoQ ameliorates experimental mouse colitis by suppressing NLRP3 inflammasome-mediated inflammatory cytokines. BMC Med. 11, 178

2) Fang, Y., Hu, X.-H., Jia, Z.-G., Xu, M.-H., Guo, Z.-Y., and Gao, F.-H. (2012) Tiron protects against UVB-induced senescence-like characteristics in human dermal fibroblasts by the inhibition of superoxide anion production and glutathione depletion. Australas. J. Dermatol. 53, 172–180

3) Sztretye, Mónika, et al. "Astaxanthin: A potential mitochondrial-targeted antioxidant treatment in diseases and with aging." Oxidative medicine and cellular longevity 2019 (2019).