UT Southwestern Medical Center researchers find that an FDA-approved drug to treat high blood pressure seems to extend life span in worms via a cell signaling pathway that may mimic caloric restriction.
The drug, hydralazine, extended life span about 25 percent in two strains of C. elegans (roundworms), one a wild type and the other bred to generate high levels of a neurotoxic protein called tau that in humans is associated with Alzheimer’s disease.
“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 Dr. Hamid Mirzaei, Assistant Professor of Biochemistry at UT Southwestern and senior author of the study, published today 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, Dr. 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 said.
The UT Southwestern researchers were searching for a chemical probe they could use in experiments to identify proteins that get oxidized and become toxic during aging. Their screen for a substance that would cross the blood-brain barrier and be nontoxic led them to hydralazine.
“Age-related neurodegenerative diseases are devastating, and those conditions are on the rise due to the increase in the life span of humans. For that reason, it is important to develop treatments to maintain human health as long as possible,” said Dr. Mirzaei, who is also an investigator in the Center for Alzheimer’s and Neurodegenerative Diseases, part of the Peter O’Donnell Jr. Brain Institute at UT Southwestern.
The researchers did in vivo (in a living creature) and in vitro (in a lab dish) studies on the worms and also studied human cells from a pediatric cancer called neuroblastoma. Compared with untreated controls, roundworms treated with the drug showed about a 25 percent increase in life span (from 15-18 days to about 20-23 days), the team reported.
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 said.
To test the potency of hydralazine in the context of neurodegenerative disease, the scientists used a high dose of a chemical stressor called rotenone that is associated with increased risk of Parkinson’s disease in humans exposed to high doses. They found that hydralazine provided a significant amount of neuroprotection, Dr. Mirzaei said. The drug also showed a significant decrease in tau toxicity in the C. elegansmodel of Alzheimer’s disease, 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.
The Latest on: Life extension
- EU Juncker: If Britain asked for an extension, no one would oppose it on February 18, 2019 at 11:11 am
if Britain requested an extension of Brexit talks, no one in Europe would oppose it he has no time frame of mind for life extension finds it hard to imagine Brits voting in European parliament electio... […]
- Can Anti-Aging Treatments Offer Abundant Life? on February 15, 2019 at 12:14 pm
He sees science and technology as part of God’s vision for the world, which, for him, includes radical life extension. Redding points to Isaiah 65, where “one who dies at a hundred years will be thoug... […]
- Bill Maris Fund Section 32 Notches Two Wins with Life Science Exits on February 15, 2019 at 9:07 am
according to a New Yorker article from 2017 about Silicon Valley’s passionate pursuit of life extension. While Calico hasn’t talked much about what it’s been up to since its launch ... […]
- New Academy to Boost the Image of Life Extension on February 13, 2019 at 10:21 am
A collection of sixteen senior scientists have created an academy in Boston in order to showcase the important work currently being conducted on human aging and how researchers are developing ways to ... […]
- Global Oral & Dental Probiotics Market 2019 – Now Foods, Hyperbiotics, Oragenics, Life Extension, Lallemand on February 6, 2019 at 4:31 am
Global Oral & Dental Probiotics Market report has been prepared based on an in-depth market analysis with inputs from industry experts. In-depth studies include keyword123 Market drivers, latest chall... […]
- Shelf Life Extension Ingredients Market – Worldwide Insights on Threats 2028 on February 5, 2019 at 7:56 pm
San Francisco, CA -- (SBWIRE) -- 02/05/2019 -- Growing emphasis on the food safety and longer shelf life has played an important role in the development of ingredients that aid in food preservation. T... […]
- OceanaGold Receives Permits for the Martha Underground and Mine Life Extension at Waihi on February 4, 2019 at 10:46 pm
MELBOURNE, Feb. 5, 2019 /CNW/ - OceanaGold Corporation (TSX: OGC | ASX: OGC) (the "Company") is pleased to announce that the statutory appeal period related to the Martha Underground Project ("Martha ... […]
- Report Finds a Strong Relationship Between Crypto-Advocates and Life Extension on January 30, 2019 at 4:00 pm
Cryptocurrency enthusiasts and believers in life extension go hand in hand these days, according to a report by Breaker columnist Julia Herbst. The chief science officer of SENS (Strategies for Engine... […]
- Work to start on first phase of CH-146 Griffon upgrade and life extension on January 27, 2019 at 8:53 am
Bell Helicopter Textron Canada will start the process to upgrade and extend the operating life of the Canadian Forces Griffon helicopter fleet with initial work needed to determine how to proceed with ... […]
via Google News and Bing News