More Robust Data on the Effect of Mitochondrially Targeted Antioxidants on Fly Life Span

In recent years a few research groups have been working on a class of antioxidant compounds that can be ingested but nonetheless target themselves to mitochondrial in our cells. These compounds extend life in laboratory animals, probably by soaking up reactive free radical compounds emitted by mitochondria in the course of their operation, and thus preventing some of the damage that mitochondria cause to themselves. This damage is significant in aging, one of the root causes of degeneration and age-related disease.

It is worth noting that all of the commonly available antioxidant compounds you can buy and ingest do nothing for life span or health, according to many, many studies. They don't target mitochondria, and in fact probably even cause some harm by blocking hormetic processes that use free radical signaling to boost repair mechanisms in tissue.

Here is a paper providing more data on the effects of the best known class of mitochondrially targeted antioxidant:

Previously, extremely low [concentrations] of the mitochondria-targeted plastoquinone derivative SkQ1 (10-(6'-plastoquinonyl) decyltriphenylphosphonium) were shown to prolong the lifespan of male and female Drosophila melanogaster by about 10%. Using long-term monitoring of SkQ1 effects on the Drosophila lifespan, we analyzed different integral parameters of Drosophila survival and mortality under SkQ1 treatment. Meta-analysis was used to evaluate the average SkQ1 effect measured in terms of standard deviation. The effect appeared to be 0.25 for females and 0.18 for males.

The SkQ1 effects on the Drosophila lifespan were reproducible over six years and showed no relationship to fluctuations in the mean lifespan of the w ( 1118 ) line used in the experiments, methods of preparation and administration of the drug, seasons, or calendar years. Adding SkQ1 to fly food was associated with a reduction in early mortality and a decrease in random variation in lifespan. [The data] indicated that feeding flies SkQ1 reduced the rate of fall of fly vitality and, consequently, slowed aging. These findings indicated that the SkQ1 effect on lifespan was associated with both elevation of life quality and slowing of aging.



Perhaps this is connected with observations that mitochondrial respiration may be involved in driving cells along the differentiation trajectory from "stemness" through to senescence. One of many references -

"Empowering self-renewal and differentiation: the role of mitochondria in stem cells"

Could SkQ1 mimic the hypoxic cellular environment that preserves stemness?

Posted by: Lou Pagnucco at October 18th, 2012 10:35 AM

@Lou Pagnucco: At this point, I'm more inclined to believe that it's a matter of general effects on tissue. Where stem cells are concerned that means less of the signaling changes that suppress their activities because there is less global mitochondrial damage to cause signaling to change in the niches and elsewhere. That's no doubt a gross simplification of what's actually going on, sadly.

Posted by: Reason at October 18th, 2012 11:37 AM

Many of us think that cellular "damage" is irreversible change analogous to damage in an intricate, impossible to repair, mechanical system like an old spring-gear watch. But, a cell is vastly more complex, yet most can be reprogrammed and rejuvenated even when senescent.

My best guess is that mitochondrial respiration/leakage, cellular differentiation rate, resistance to apoptosis, and the pace epigenetic programming are tightly coupled and determine speed of maturation(=aging).

BTW, here is another paper I found interesting -
"Mitochondria in Control of Cell Fate"

Posted by: Lou Pagnucco at October 18th, 2012 10:29 PM
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