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[trance]

Not sure if this has been mentioned already -- I did a search but could not find it in the forums here -- but here's a recent paper on many mitochondrial targeted modalities. It discusses many of the current topics here, eg MitoQ, SkQ, peptides, nanoparticles, etc. -- Trance


Abstract:

Populations in many nations today are rapidly ageing. This unprecedented demographic change represents one of the main challenges of our time. A defining property of the ageing process is a marked increase in the risk of mortality and morbidity with age. The incidence of cancer, cardiovascular and neurodegenerative diseases increases non-linearly, sometimes exponentially with age. One of the most important tasks in biogerontology is to develop interventions leading to an increase in healthy lifespan (health span), and a better understanding of basic mechanisms underlying the ageing process itself may lead to interventions able to delay or prevent many or even all age-dependent conditions.

One of the putative basic mechanisms of ageing is age-dependent mitochondrial deterioration, closely associated with damage mediated by reactive oxygen species (ROS). Given the central role that mitochondria and mitochondrial dysfunction play not only in ageing but also in apoptosis, cancer, neurodegeneration and other age-related diseases there is great interest in approaches to protect mitochondria from ROS-mediated damage. In this review, we explore strategies of targeting mitochondria to reduce mitochondrial oxidative damage with the aim of preventing or delaying age-dependent decline in mitochondrial function and some of the resulting pathologies. We discuss mitochondria-targeted and -localized antioxidants (e.g.: MitoQ, SkQ, ergothioneine), mitochondrial metabolic modulators (e.g. dichloroacetic acid), and uncouplers (e.g.: uncoupling proteins, dinitrophenol) as well as some alternative future approaches for targeting compounds to the mitochondria, including advances from nanotechnology.

Full Paper:

 Mitochondria-Targets.pdf   1.39MB   25 downloads


PubMed:

http://www.ncbi.nlm....pubmed/23022622


 Image1.jpg   104.83KB   10 downloads

Design of a possible mitochondria-targeted nano-material, bearing several functional groups (e.g. mitochondriotropics and fluorescent probes) and encapsulating antioxidants in their inner core.

[Kevnzworld]

The best commercially available mitochondrial antioxidant that we currently have is PQQ .
SKQ1 looks intriguing. I'm always wary of science that emanates out of Russian labs. There often seems to be a commercial motivation driving it. ( St Petersburg institute of bioregulation and gerontology ).
That being said, I hope there is more research and studies done to see if SKQ1 is for real.
From the study :
Here we conclude that SkQ1 not only prevented age-associated hormonal alterations but partially reversed them. These results suggest that supplementation with low doses of SkQ1, even in chronologically and biologically aged subjects seem to be a promising strategy to maintain health and retard the aging process.
http://impactaging.c...ull/100493.html

[trance]

FWIW -- Section from the report about fullerenes and C60 ...


7.4. Carbon based nano-antioxidants

In addition to solid nanoparticles, another allotropic form of carbon (besides nanotubes) known as fullerene has been shown to be an antioxidant in vitro (Andrievsky et al., 2009; Cai et al., 2008; Chen et al., 2004; Elswaifi et al., 2009; Krusic et al., 1991; Sun, 2006) through a complex mechanism: fullerenes seem to act as 1) protectants against oxidative damage by crossing the cell membrane and localizing preferentially in the mitochondria; and 2) efficient radical scavengers, through a hydrated free radical recombination (self-neutralization) of hydroxyl radicals (•OH), which is catalyzed by specific water structures ordered by the fullerene molecules. Therefore, it has been suggested that efficient uptake and precise subcellular distribution at the mitochondrial level are key requirements to inhibit ROS formation (Ali et al., 2004; Foley et al., 2002).

However, some contrasting observations were associated with this material, since fullerenes and their derivatives have also been reported to increase oxidative stress. Data by Gharbi et al. indicate that aqueous suspensions of fullerene (C60) protected against toxicity induced by carbon tetrachloride (CCl4) (Gharbi et al., 2005). In fact, 24 h after CCl4 injection, most animals pretreated with C60 at high doses (≥0.5 g/kg), presented livers with normal morphology (Ali et al., 2004; Foley et al., 2002). CCl4 undergoes metabolism by cytochrome P450 enzymes and generates a reactive trichloromethyl radical CCl3• which, in the presence of oxygen, gives rise to trichloromethylperoxy radical CCl3OO and lipid peroxidation. Therefore, the mechanism of protection against CCl4 toxicity in rats was proposed to be due to the ability of C60 to scavenge these radicals in vivo.

In addition, in a recent study, oral administration of C60 suspended in olive oil (0.8 mg/ml) at repeated doses (1.7 mg/kg of body weight) resulted in almost doubling of lifespan and significant protection in an experimental model of CCl4 intoxication in rats and erratum (Baati et al., 2012a,b). These findings are encouraging but should be considered carefully, especially the animal lifespan results, as olive oil administration alone already resulted in significant increase in median lifespan, raising questions regarding the choice of solvent for C60 administration. Strikingly, median lifespan was extended to 42 months in C60-treated rats, compared to 22 months in water controls and 26 months in the olive oil group. The median lifespan in the C60 group is surprising and needs to be validated in future in vivo studies to make sure the results are reproducible.

Another interesting work has been recently published by Cirillo et al. in which a covalent functionalization based on radical grafting was used to incorporate gallic acid on carbon nanotubes without losing any of its antioxidant properties. This result, although limited to preliminary in vitro studies and in the absence of any cytotoxicity evaluation (which is important, because gallic acid can readily oxidize to produce ROS Wee et al., 2003), may pave the way for the integration of radical scavengers onto suitable nano-carriers through new methods of covalent linkage (Cirillo et al., 2011)

Despite that, no categorical statement can be made about the safety of these carbon-based agents; differences in the purity of the samples, in the incorporation of bioactive molecules through several chemical procedures and in the doses used during the experiments do not allow any definite conclusion about the documented higher efficacy or their toxicological profile. Many questions regarding the safety of nanoparticles are still unanswered, the main concern being their ability to trigger intense chemical reactions and anomalies as nanospecies, while escaping from the normal phagocytic defenses and depositing into organs and tissues. At the moment, available information concerning the health risks to the environment and humans is poor. The encouraging results that have been achieved so far suggest that they are worth further investigation, although it is imperative to fully address the biocompatibility of these formulations before concluding that nano-carriers are safe delivery systems.