27 December 2017

Another potential geroprotector

Researchers at the University of Texas Southwestern Medical Center, working under the guidance of Dr. Hamid Mirzaei, have found that the drug hydralazine, approved by the U.S. Food and Drug Administration (FDA), increases the life expectancy of C.elegans roundworms by about 25% by activating a signaling pathway simulating the effects of low-calorie diets.

As part of the study, the authors were searching for a chemical probe that, under experimental conditions, would allow them to identify proteins that oxidize and become toxic during aging. Screening of non-toxic compounds potentially capable of penetrating the blood-brain barrier has led them to hydralazine.

Subsequently, experiments conducted on two nematode lines, one of which was represented by wild–type individuals, and the second by worms with an increased level of neurotoxic tau protein associated with Parkinson's disease in humans, demonstrated the ability of hydralazine to increase the life expectancy of worms of both lines by about 25% (from 15-18 to 20-23 days) compared with individuals control groups.

The results of a number of biochemical experiments have shown that this effect is due to the launch of a signaling mechanism mediated by the SKN-1 transcription factor, simulating the effects of a low-calorie diet. This transcription factor is an analog of the human factor NRF2, known for its primary role in the development of the reaction to oxidative stress and the regulation of life expectancy. According to Dr. Mirzai, oxidative stress is one of the iconic manifestations of aging and neurodegenerative diseases such as Alzheimer's and Parkinson's diseases.

To test the potential activity of hydralazine against neurodegenerative diseases, the researchers used a high dose of a chemical stress factor known as rotenone. Exposure to this compound is associated with an increased risk of developing Parkinson's disease. The obtained results demonstrated a pronounced neuroprotective effect of hydralazine. In addition, the use of the drug significantly reduced the toxicity of tau protein in nematodes with simulated Alzheimer's disease.

Based on the results obtained, the authors believe that hydralazine is a promising candidate for conducting clinical trials involving patients suffering from age-related diseases. Theoretically, this drug can be used to improve the overall health of the elderly. However, Dr. Mirzai emphasizes that the work carried out by him and his colleagues is only the first step in this direction and there is still a lot of work to be done to confirm the results obtained.

Article by Esmaeil Dehghan et al. Hydralazine induces stress resistance and extends C. elegans lifespan by activating the NRF2/SKN-1 signaling pathway published in the journal Nature Communications.

Evgeniya Ryabtseva

Portal "Eternal youth" http://vechnayamolodost.ru According to the University of Texas Southwestern Medical Center: FDA-approved high blood pressure drug extends life span in roundworms.

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