Posted on Apr 04, 2018, 10 p.m.
A drug approved by the FDA for treatment of high blood pressure has been found to extend the lifespan of roundworms via a cell signalling pathway that mimics caloric restriction according to researchers from Southwestern Medical Center.
It has been observed by researchers that hydralazine appears to extend the lifespan in 2 strains of C.elegan roundworms by about 25%, with one of the worms being a wild type and the other bred to generate high level of neurotoxic tau protein which is associated with Alzheimer’s disease.
Researchers say that this is the first known report of hydralazine activating the NRF2/SKN-1 signaling pathway, and have found that hydralazine extended lifespan as well as or better than other potential anti-aging compounds including metformin and curcumin; and also appeared to maintain health as measured by tests of flexibility and wiggling speed.
The body’s ability to protect against damaging oxygen free radicals decreases with age, NRF2 pathway protects human cells from oxidative stress. A hallmark of neurodegenerative disease and aging is oxidative stress which is believed to result cumulatively from infectious and inflammatory illness that occur throughout life. SKN-1 which is a C.elegans transcription factor corresponds to NRF2 in humans, both of which play important roles in their respective species response to oxidative stress and lifespan explains Dr. Hamid Mirzaei.
Researchers conducted both in vitro and in vivo studies on the worms as well as studied human neuroblastoma cancer cells. Worms treated with hydralazine showed 25% increase in lifespan. Results of a series of biochemical experiments indicated that the extension was dependent on the worms’ SKN-1 pathway via a mechanism that mimics caloric restriction.
Testing hydralazine potency in the context of neurodegenerative disease was conducted by using a high dose of rotenone chemical stressor which is associated with increased risk of Parkinson’s disease, and found that significant amounts of neuroprotection was provided by hydralazine; it also showed significant decreases in tau toxicity in the Alzheimer’s disease model.
Based on study results researchers suggest that hydralazine may be a candidate in clinical trial for the treatment of age related human disorders as it may also offer other general health benefits to the aging population. This study shows promise as a first step in the process, but other studies are needed to corroborate it.
Neurodegenerative age related disease can be very devastating, occurrence of these diseases are increasing due to increases in lifespan, for this reason it is important to develop treatments to maintain quality of human health for as long as possible.
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UT Southwestern Medical Center