DNA damage and mutation[ edit ] 8-Hydroxydeoxyguanosine Further information: Damage and mutation are fundamentally different.
Image source More than a year has passed since publication of the November blog entry Buckyballs, health and longevity — state of knowledgeIt will be another year or two before we know whether researchers are capable of reproducing the extraordinary longevity impacts on rats reported in the publication The prolongation of the lifespan of rats by repeated oral administration of  fullerene.
But we can continue seriously discussing and speculating about the third question now, and that is the focus of this blog entry. In particular, a new mechanism is proposed for how C60 can possibly drastically reduce ROS and its pro-aging consequences.
Readers are referred to the earlier blog entry for in-depth background. Some of these are reviewed here along Comparative analysis of dna damage in several relevant topics not previously well-covered. C60 might significantly reduce reactive oxygen species produced by leaky mitochondria and associated cell damage, but not by a direct antioxidant effect.
In our minds, this is probably the central new finding. DNA damage triggers the DNA damage response ddr which in turn triggers p53 activation which can then inhibit PGC-1b, resulting in the inhibition of gene transcription for nuclear-encoded mitochondrial proteins.
Thus, this mechanism can induce high mitochondrial ROS generation, Warburg-type metabolism, increased oxidative stress leading to further negative effects such as more DNA damage.
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 p It has previously been speculated that C60 buckyballs penetrate the cell and mitochondrial membranes and exercise an antioxidant ROS-quenching effect upon arriving within the mitochondria.
Another very interesting hypothesis has been suggested in That hypothesis is that C60 serves to drastically reduce the production of the superoxide radical via reducing the electric potential across mitochondrial membranes. Instead of cleaning up a dangerous superoxide radical via an antioxidant, this mechanism, would serve to prevent creation of that radical in the first place.
In the present study we confirm this hypothesis using computer modeling based on Density Functional Theory.
We propose here that C60 has an ability to acquire positive charge by absorbing inside several protons and this complex could penetrate into mitochondria. Such a process allows for mild uncoupling of respiration and phosphorylation.
This, in turn, leads to the decrease in ROS production. Here we briefly report on the theoretical test of the very possibility of protons to pass through the surface of C60 fullerene to become confined within latter thus possibly decreasing the transmembrane electric field gradient when fullerene crosses the mitochondria membrane.
Quantumchemical calculations within Density Functional Theory are employed as a means of checking described scenario. Recently Baati et al. Besides, rats treated with fullerene C60 demonstrated high resistance to carbon tetrachloride capable of triggering generation of huge amounts of harmful reactive oxygen species.
Consequently, fullerene C60 was proposed to have high antioxidant activity in vivo. Geroprotective activity of C60 fullerene found experimentally in  is much higher than those of the most powerful reactive oxygen species scavengers.
Reactive oxygen species may cause oxidative damage.
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.
The outer side of inner membrane of mitochondria has positive charge and the inner side has negative charge. Superoxide is created as a result of the cross-membrane charge differential, the amount being a nonlinear function of the differential.
In the case of C60, the modeling studies suggest that the fullerenes are initially electrically neutral and penetrate easily to the center of the mitochondrial membranes.
There, a fullerene may pick up as many as six protons, according to the quantum wave-function model. The electrical gradient then sucks the positively charged fullerene across the inner mitochondrial membrane into the interior of the mitochondria.
C60 fullerene molecules enter the space between inner and outer membranes of mitochondria, where the excess of protons has been formed by diffusion. In this compartment fullerenes are loaded with protons and acquire positive charge distributed over their surface. In this case the transmembrane potential is reduced, which in turn significantly reduces the intensity of superoxide anion-radical production.
Once a positively charged fullerene is inside the mitochondria, the charge differential between the inner and the outer membrane is automatically reduced.Comparative phosphoproteomic analysis of checkpoint recovery. Given the importance of kinases and phosphatases in the DNA damage response and the cell cycle machinery, we reasoned that protein phosphorylation and dephosphorylation must play an important role in recovery.
Comparative analysis of different laser systems to study cellular responses to DNA damage in mammalian cells. is the use of a laser microbeam to irradiate a defined submicron region in the cell nucleus allowing single cell analysis of DNA damage recognition/response.
ORIGINAL ARTICLEAndrology Comparative analysis of three sperm DNA damage assays and sperm nuclear protein content in couples undergoing assisted reproduction treatment. The fungal toxin, Ochratoxin A (OTA), is a common contaminant in human food and animal feed.
The present study evaluated micronucleus (MN) induction by OTA in comparison with its ability to induce cytotoxicity and DNA damage in two mammalian cell lines, CHO-K1-BH 4 Chinese hamster ovary cells and TK6 human lymphoblastoid cells.
Micronuclei were evaluated by flow cytometry, cytotoxicity was. Detection of circulating tumor DNAs (ctDNAs) in cancer patients is an important component of cancer precision medicine ctDNAs. Compared to the traditional physical and biochemical methods, blood-based ctDNA detection offers a non-invasive and easily accessible way for cancer diagnosis, prognostic determination, and guidance for treatment.
Since scientists have known that people of Eurasian origin have inherited anywhere from 1 to 4 percent of their DNA from Neanderthals.