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Reducing Reactive Oxygen Species And Its Pro-Aging Consequences
C60 – Reducing Reactive Oxygen Species And Its Pro-Aging Consequences
C60 can possibly drastically reduce Reactive oxygen species and its pro-aging consequences.
C60 might significantly reduce reactive oxygen species produced by leaky mitochondria and associated cell damage, but not by a direct antioxidant effect.
An important recent paper by David Sinclair and his associates describes how such ROS can be induced by age-related absence of sufficient NAD+ in the cell nucleus leading to a state of pseudohypoxia and insufficient expression of mitochondrially-coded protective genes
DNA damage triggers the DNA damage response which in turn triggers p53 activation which can then inhibit PGC-1b, resulting in the inhibition of gene transcription for nuclear-encoded mitochondrial proteins. This mechanism can induce high mitochondrial ROS generation, Warburg-type metabolism, increased oxidative stress leading to further negative effects such as more DNA damage.
DNA damage can then lead to PARP-1 activation, which then can deplete nuclear NAD+, which then will stop SIRT1, SIRT6, and SIRT7 function. This then leads to a pseudohypoxic state of the nucleus due to HIF-1a stabilization. This in turn leads to inadequate TFAM, which then results in inadequate expression of mitochondrially-encoded proteins for electron transport. Thus, mitochondrial dysfunction can be triggered by telomere-dependent, DDR-mediated activation of p53.
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- The outer mitochondrial membrane is charged positively and the inner membrane is charged negatively. This is because free electrons are spun off in the complexes in the electron transfer chain. As the chain becomes less efficient and there is decline in expression of mitochondrial antioxidants, the more there is a charge differential. “Accumulation of Skulachev ions in the mitochondria is based on the transmembrane potential difference generated as a result of electron transport chain activity. The outer side of inner membrane of mitochondria has positive charge and the inner side has negative charge.” The actions of the electron transport chain involve four complexes, and you can get a fair idea how they work by viewing one of these animations.
- Superoxide is created as a result of the cross-membrane charge differential, the amount being a nonlinear function of the differential. “The specific feature attributable to the generation of ROS by mitochondria is related to the fact that the higher is the membrane potential (the larger is the difference in the concentration of protons inside and outside the mitochondria), the higher is the level of the superoxide anion production. As it was shown [29], there is steep dependence of mitochondrial superoxide-anion-radical generation on transmembrane potential (Δ). Even a small (10–15%) decline of Δ resulted in tenfold lowering of ROS production rate.”
Liposomal encapsulated C60 fullerenes are not toxic and have an anti-cancer effect, whereas non-encapsulated C60 fullerenes do NOT have an anti-cancer effect.
The following publication suggests that another benefit of C60 could be an enhancement of mitophagy. If this applies, C-60 might have three different positive effects:
http://www.ncbi.nlm.nih.gov/m/pubmed/21173115/?i=4&from=/23620051/related
- Direct antioxidant effect once it enters a mitochondrion
- Reduction of the production of superoxide
- Enhancement of mitophagy.
