Paths to the Development of Mitochondrially Targeted Antioxidants

Antioxidant compounds can extend life in mice provided they are localized to the mitochondria - which doesn't happen for anything you can presently buy in a bottle. Near all antioxidants that can be ingested, injected, or otherwise introduced into the body do nothing of any great significance to healthy life span, and may even be detrimental by interfering in the processes of hormesis that help to maintain and improve health.

As I'm sure you know by now, mitochondria are the cell's powerplants, converting food into the chemicals used by cells to store and transport energy. They also generate damaging free radicals - such as reactive oxygen species - as a consequence of their operation. These free radicals in turn tend to damage mitochondria in ways that eventually snowball towards larger and larger consequences in the body: this mitochondrial damage is in fact one of the important root causes of aging.

In the field of targeted antioxidants, researchers have gene engineered mice to generate more natural antioxidants in their mitochondria. A group in Russia has been quite active in working on SkQ1, an ingested compound that targets mitochondria, and Australian researchers have a similar chemical under development. Out of these lines of work, a number of studies show healthy life extension and other benefits in mice.

Unfortunately, raising funds to develop any sort of longevity enhancing therapy for humans - even one with a probably small effect, and which looks exactly like run of the mill drug discovery and evaluation - runs right into the roadblock of the FDA. Since the FDA bureaucrats don't recognize aging as a medical condition, they will not approve any commercial application sold to that end. Since there can be no selling, and hence no potential for profit, no-one will fund the research and development. All potential approaches to extending longevity are instead sidelined into becoming just another therapy for the late stages of an age-related condition like diabetes. Wasted time, wasted effort.

From where I stand, the preferable ways forward are to tear down the FDA (for all that this once grand country seems very lacking in revolutionary spirit these days), or take the commercial development overseas, which may force much the same end result in the fullness of time. But many groups choose to stay within the US regulatory straitjacket.

For the targeted antioxidant development, two potential lines of within-the-system development spring to mind. Firstly, as a therapy for sepsis:

Bench-to-bedside review: Targeting antioxidants to mitochondria in sepsis

Development of organ dysfunction associated with sepsis is now accepted to be due at least in part to oxidative damage to mitochondria. Under normal circumstances, complex interacting antioxidant defense systems control oxidative stress within mitochondria. However, no studies have yet provided conclusive evidence of the beneficial effect of antioxidant supplementation in patients with sepsis. This may be because the antioxidants are not accumulating in the mitochondria, where they are most needed. Antioxidants can be targeted selectively to mitochondria by several means. This review describes the in vitro studies and animal models of several diseases involving oxidative stress, including sepsis, in which antioxidants targeted at mitochondria have shown promise, and the future implications for such approaches in patients.

Secondly, it appears that wound healing, and especially in the old, may benefit from mitochondrially targeted antioxidants:

It is shown that the novel mitochondria-targeted antioxidant SkQ1 [stimulates] healing of full-thickness dermal wounds in mice and rats. Treatment with nanomolar doses of SkQ1 in various formulations accelerated wound cleaning and suppressed neutrophil infiltration at the [early steps] of inflammatory phase. SkQ1 stimulated formation of granulation tissue and increased the content of myofibroblasts in the beginning of regenerative phase of wound healing. Later this effect caused accumulation of collagen fibers. Local treatment with SkQ1 stimulated re-epithelization of the wound. Lifelong treatment of mice with SkQ1 supplemented with drinking water strongly stimulated skin wounds healing in old (28 months) animals. In an in vitro model of wound in human cell cultures, SkQ1 stimulated movement of epitheliocytes and fibroblasts into the 'wound'. Myofibroblast differentiation of subcutaneous fibroblasts was stimulated by SkQ1.

It is suggested that SkQ1 stimulates wound healing by suppression of the negative effects of oxidative stress in the wound and also by induction of differentiation. Restoration of regenerative processes in old animals is consistent with the 'rejuvenation' effects of SkQ1, which prevents some gerontological diseases.

Either of these uses is probably sufficiently large to support a fair-sized research and development effort in the US, should the present lines of research continue to show promise and benefit. But it won't be work on slowing aging any more - which is perhaps the most pernicious effect of the FDA roadblock on applied longevity science.

ResearchBlogging.orgGalley HF (2010). Bench-to-bedside review: Targeting antioxidants to mitochondria in sepsis. Critical care (London, England), 14 (4) PMID: 20804578

Demianenko IA, Vasilieva TV, Domnina LV, Dugina VB, Egorov MV, Ivanova OY, Ilinskaya OP, Pletjushkina OY, Popova EN, Sakharov IY, Fedorov AV, & Chernyak BV (2010). Novel mitochondria-targeted antioxidants, "Skulachev-ion" derivatives, accelerate dermal wound healing in animals. Biochemistry. Biokhimiia, 75 (3), 274-80 PMID: 20370605


Years back I'd heard animal supplementation helped to prevent the age related morphological changes that occur in mitochondria.

I've also heard of the combination of alpha lipoic acid and acetyl-l-carnitine as probably aiding mitochondrial function.

It'd be interesting to see the effects of combined ginkgo + alpha lipoic acid + acetyl-l-carnitine.

Posted by: Cameron at September 20th, 2010 8:57 PM

Clarification on previous post:

"Years back I'd heard animal supplementation helped to prevent the age related morphological changes that occur in mitochondria."

What I meant there, was ginkgo supplementation.

Posted by: Cameron at September 21st, 2010 7:50 PM
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