13 December 2011

The association of free radicals with aging has not been confirmed

Oxidative stress: is it as harmful as it was supposed to be?
LifeSciencesToday based on the materials of the German Cancer Research Center – 
Oxidative stress: Less harmful than suspected?Arterial calcification and coronary heart disease, neurodegenerative diseases such as Parkinson's disease and Alzheimer's disease, cancer and even the aging process itself are assumed to be partially caused or accelerated by oxidative stress.

Oxidative stress is observed when there is an excess of so-called reactive oxygen species (ROS) in the tissues.

"However, until now, no one has been able to directly observe oxidative changes in a living organism and, of course, how these changes are associated with pathological processes," says Associate Professor Tobias Dick, PD, from the German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ). "Rather non-specific or indirect methods were used to establish what oxidative processes are really going on in the body."

For the first time, Dr. Tobias Dick and his colleagues were able to observe oxidative processes in a living organism. In a study conducted jointly with Dr. Aurelio Teleman (also from DKFZ), he introduced biosensor protein genes into the genetic material of fruit flies. These biosensors are specific to several different oxidants and show the oxidative status of each cell by emitting a light signal – in real time, throughout the body and throughout its life.

Yellow light signals emitted by biosensors,
indicate the production of oxidants in the tissue of a migrating fly larva.
(Photo: Tobias Dick, Deutsches Krebsforschungszentrum)

Scientists have found that the level of formation of oxidants in different types of tissues of fly larvae is different. Thus, the mitochondria of blood cells produce significantly more oxidants than, for example, in the mitochondria of intestinal or muscle cells. In addition, the behavior of individual larval tissues is reflected in the production of oxidants: by the oxidative status of adipose tissue, researchers could distinguish whether the larvae were eating or moving.

Until now, many scientists believe that the aging process is associated with a general increase in the level of oxidants throughout the body. However, this has not been confirmed by observations carried out throughout the life of adult animals. German researchers were surprised that almost the only age-related increase in the level of oxidants was observed in the intestines of flies. Moreover, when comparing flies with different lifespans, it turned out that the accumulation of oxidants in the intestinal tissue of insects with a longer lifespan even accelerated. Thus, the researchers found no evidence of the oft-stated assumption that the lifespan of an organism is limited by the production of harmful oxidants.

Antioxidants are often advertised as health-promoting substances, as they are a protection against oxidative stress, although comprehensive studies have so far failed to provide convincing evidence for this. Dr. Dick and his colleagues fed their flies with N-acetylcysteine (NAC), a substance with an antioxidant effect that some scientists consider suitable for protecting the body from supposedly dangerous oxidants. Interestingly, there were no signs of a decrease in the amount of oxidants in such flies. On the contrary, the researchers were surprised to find that NAC contributed to a significant increase in the production of oxidants by mitochondria of cells of various tissues.

"Much of what we observed with the help of biosensors in flies came as a surprise to us. It is obvious that most of the data obtained on isolated cells cannot simply be transferred to the situation in a living organism," Dr. Dick summarizes the results. "The example of NAC shows that at present we are not able to predictably influence oxidative processes in a living organism using pharmacological means. Of course, we can't just transfer this data from flies to humans. Our next goal is to use biosensors to monitor oxidative processes in the mammalian body, especially during inflammatory reactions and the development of tumors."

An article about the study by German scientists was published in the prestigious scientific journal Cell Metabolism (Albrecht et al., In vivo mapping of hydrogen peroxide and oxidized glutathione reveals chemical and regional specificity of redox homeostasis).

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