Hydralazine, an FDA-approved high blood pressure medication, has been shown to extend healthy life span in Caenorhabditis elegans and have neuroprotective properties against endogenous and exogenous stressors. It could be a viable candidate for the treatment of age-related disorders, according to UT Southwestern Medical Center researchers.
Hydralazine extended life span about 25% in two strains of C. elegans, one a wild type and the other bred to generate high levels of tau, which is associated with Alzheimer's disease in humans.
"This is the first report of hydralazine treatment activating the NRF2/SKN-1 signaling pathway. We found the drug extends the life span of worms as well as or better than other potential anti-aging compounds such as curcumin and metformin. The treatment also appeared to maintain their health as measured by tests of flexibility and wiggling speed," said Hamid Mirzaei, assistant professor of biochemistry at UT Southwestern and senior author of the study, published yesterday in Nature Communications.
The NRF2 pathway protects human cells from oxidative stress. The body's ability to protect itself against damaging oxygen free radicals diminishes with age, he said.
One of the hallmarks of aging and neurodegenerative diseases such as Alzheimer's and Parkinson's is oxidative stress, which is believed to result cumulatively from inflammatory and infectious illnesses throughout life, Mirzaei explained. SKN-1, a C. elegans transcription factor, corresponds to NRF2 in humans. Both play a pivotal role in their respective species' responses to oxidative stress and life span, he explained.
The results of a series of biochemical experiments indicated that the hydralazine-linked life span extension was dependent on the worms' SKN-1 pathway via a mechanism that appeared to mimic caloric restriction, he added.
"Based on these results, we suggest that hydralazine may be a good candidate for clinical trials for the treatment of age-related disorders in humans as it may also offer general health benefits to the aging population," he said. He stressed that this study is a promising first step, but further studies are needed to corroborate it.