Clearing out the clutter: ‘senolytic’ drugs improve vascular health in mice

Kurzweil AI - 56 min 43 sec ago

(Left) Normal coronary artery with normal blood flow. Right: a coronary artery narrowed by plaque, limiting the flow of oxygen-rich blood through the artery. (credit: NIH)

Mayo Clinic researchers have demonstrated the first study in which repeated treatments to remove senescent cells (cells that stop dividing due to age or stress) in mice improve age-related vascular conditions — and may possibly reduce cardiovascular disease and death.

The researchers intermittently gave the mice a cocktail of two senolytic drugs (ones that selectively induce cell death): dasatinib (a cancer drug, trade name Sprycel) and quercetin*. The drugs cleared (killed off) senescent cells in naturally aged and atherosclerotic mice. The treatment did not reduce the size of plaques in mice with high cholesterol, but did reduce calcification of existing plaques on the interior of vessel walls.**

The findings appear online (open access) in Aging Cell.

“Our finding that senolytic drugs can reduce cardiovascular calcification is very exciting, since blood vessels with calcified plaques are notoriously difficult to reduce in size, and patients with heart-valve calcification currently do not have any treatment options other than surgery,” says Jordan Miller, Ph.D., Mayo cardiovascular surgery researcher and senior author of the paper.

“While more research is needed, our findings are encouraging that one day removal of senescent cells in humans may be used as a complementary therapy along with traditional management of risk factors to reduce surgery, disability, or death resulting from cardiovascular disease.”

The coauthors include two researchers from Newcastle University. The research was supported by the National Institutes of Health, Mayo Clinic Center for Regenerative Medicine, and the Connor Group and Noaber Foundation. Drs. Kirkland, Tchkonia, Zhu, Pirtskhalava, and Ms. Palmer have a financial interest related to the research.

* Quercetin is found in many fruits, vegetables, leaves and grains. It can be used as an ingredient in supplements, beverages, or foods. — Wikipedia

** Prior studies at Mayo showed chronic removal of the cells from genetically-altered mice can alter or delay many of these conditions, and short-term treatment with drugs that remove senescent cells can improve the function of the endothelial cells that line the blood vessels. This study, however, looked at the structural and functional impacts of cell clearance using a unique combination of drugs on blood vessels over time. Mice were 24 months old when the drugs were administered orally over a three-month period following those initial two years. A separate set of mice with high cholesterol was allowed to develop atherosclerotic plaques for 4 months and were then treated with the drug cocktail for two months. — Mayo Clinic

Abstract of Chronic senolytic treatment alleviates established vasomotor dysfunction in aged or atherosclerotic mice

Rationale: While reports suggest a single dose of senolytics may improve vasomotor function, the structural and functional impact of long-term senolytic treatment is unknown.

Objective: To determine whether long-term senolytic treatment improves vasomotor function, vascular stiffness, and intimal plaque size and composition in aged or hypercholesterolemic mice with established disease.

Methods and Results: Senolytic treatment (intermittent treatment with Dasatinib + Quercetin via oral gavage) resulted in significant reductions in senescent cell markers (TAF+ cells) in the medial layer of aorta from aged and hypercholesterolemic mice, but not in intimal atherosclerotic plaques. While senolytic treatment significantly improved vasomotor function (isolated organ chamber baths) in both groups of mice, this was due to increases in nitric oxide bioavailability in aged mice and increases in sensitivity to NO donors in hypercholesterolemic mice. Genetic clearance of senescent cells in aged normocholesterolemic INK-ATTAC mice phenocopied changes elicited by D+Q. Senolytics tended to reduce aortic calcification (alizarin red) and osteogenic signaling (qRT-PCR, immunohistochemistry) in aged mice, but both were significantly reduced by senolytic treatment in hypercholesterolemic mice. Intimal plaque fibrosis (picrosirius red) was not changed appreciably by chronic senolytic treatment.

Conclusions: This is the first study to demonstrate that chronic clearance of senescent cells improves established vascular phenotypes associated with aging and chronic hypercholesterolemia, and may be a viable therapeutic intervention to reduce morbidity and mortality from cardiovascular diseases.

Categories: Science

Senate Passes Bill Making Internet Tax Ban Permanent

Slashdot - 1 hour 4 min ago
kheldan writes: Nearly two decades ago, Congress passed the first Internet Tax Freedom Act, establishing that — with a handful of grandfathered exceptions — local, state, and federal governments couldn't impose taxes on Internet access. Problem is, that law has had to be renewed over and over, each time with an expiration date. But today, the U.S. Senate finally passed a piece of legislation that would make the tax ban permanent.

Read more of this story at Slashdot.

Categories: Science

Google Settles Decade-Long Tax Dispute In UK

Slashdot - 2 hours 51 min ago
An anonymous reader writes: Alphabet, Inc., parent company to Google, has agreed to pay $185 million to settle UK taxes going back to 2005. The company has also agreed to adopt a new approach to taxes in the UK going forward. While this is a sizeable figure, many believe it is too little, and constitutes a sweetheart deal between the government and Google. Matt Brittin, the President of EMEA Business and Operations for Google, was a participant in a televised hearing today in which UK lawmakers questioned the $185 million settlement. He stated, "We find ourselves in the position where we are paying the tax that the tax authorities told us to pay."

Read more of this story at Slashdot.

Categories: Science

Decade of rising seas slowed by land soaking up extra water

Science Daily - 3 hours 21 min ago
New measurements from a NASA satellite have allowed researchers to identify and quantify, for the first time, how climate-driven increases of liquid water storage on land have affected the rate of sea level rise. A new study shows that while ice sheets and glaciers continue to melt, changes in weather and climate over the past decade have caused Earth's continents to soak up and store an extra 3.2 trillion tons of water in soils, lakes and underground aquifers, temporarily slowing the rate of sea level rise by about 20 percent.
Categories: Science

The NBA All-Star Game’s 24 Superstars Get Their Very Own Emoji

Wired News - 3 hours 29 min ago

Steph Curry, James Harden, and even the TNT announcers are all getting the emoji treatment that fans can tweet all weekend long.

The post The NBA All-Star Game’s 24 Superstars Get Their Very Own Emoji appeared first on WIRED.

Categories: Science

MTV Wants You to Want Your MTV News All Over Again

Wired News - 3 hours 40 min ago

With dozens of new hires, MTV News is getting serious about its future by seeking a return to its glory days.

The post MTV Wants You to Want Your MTV News All Over Again appeared first on WIRED.

Categories: Science

Male biology students consistently underestimate female peers, study finds

Science Daily - Thu, 11/02/2016 - 11:59pm
New research shows consistent gender bias among male biology undergraduate students, suggesting that they could be undermining the confidence of female students as they embark on studies in STEM disciplines.
Categories: Science

Carbon dioxide stored underground can find multiple ways to escape

Science Daily - Thu, 11/02/2016 - 11:59pm
When carbon dioxide is stored underground in a process known as geological sequestration, it can find multiple escape pathways due to chemical reactions between carbon dioxide, water, rocks and cement from abandoned wells, according to researchers.
Categories: Science

Fish larvae are better off in groups, study finds

Science Daily - Thu, 11/02/2016 - 11:59pm
A recent study provides new evidence that larvae swim faster, straighter and more consistently in a common direction when together in a group. The research is the first to observe group orientation behaviors of larval fish.
Categories: Science

A metal that behaves like water

Science Daily - Thu, 11/02/2016 - 11:59pm
Researchers have made a breakthrough in our understanding of graphene's basic properties, observing for the first time electrons in a metal behaving like a fluid. This research could lead to novel thermoelectric devices as well as provide a model system to explore exotic phenomena like black holes and high-energy plasmas.
Categories: Science

Self-Propelling Microparticles Spot Ricin In Minutes

Slashdot - Thu, 11/02/2016 - 11:59pm
ckwu writes: Tiny rocketlike particles that move around on their own in a hydrogen peroxide solution can detect trace amounts of the lethal toxin ricin within minutes. The tube-shaped, microsized particles--made of graphene oxide lined with platinum--carry sensor molecules that glow when they bind to ricin. In a dilute hydrogen peroxide solution, the platinum catalyzes the breakdown of the peroxide into water and oxygen. The oxygen bubbles shoot out one end of the tube, propelling them in the liquid like little rockets. The swimming motors could actively seek out ricin in a sample and speed up detection, paving the way towards a quick, easy way to detect the bioterrorism agent in food and water samples (without having to bring them back to a lab).

Read more of this story at Slashdot.

Categories: Science

Mommy and me: Study shows how affectionate mothering can combat the effects of maternal depression

Science Daily - Thu, 11/02/2016 - 11:50pm
Certain parenting strategies can combat the negative impacts of maternal depression on an infant, suggests the first study of its kind. The work sought to investigate how a depressed mother's neuroendocrine response to stress can program the infant's hypothalamic-pituitary-adrenal axis, a set of signals and relationships between the hypothalamus, the pituitary gland and the adrenals. The hypothalamic-pituitary-adrenal axis is responsible for creating cortisol, a hormone released in response to stress.
Categories: Science

By switching 'bait,' biologists trick plants' bacterial defense into attacking virus

Science Daily - Thu, 11/02/2016 - 11:40pm
Scientists have modified a plant gene that normally fights bacterial infection to confer resistance to a virus. The method is the first time a plant's innate defense system has been altered to deliver resistance to a new disease.
Categories: Science

First nationwide survey of climate change education

Science Daily - Thu, 11/02/2016 - 11:39pm
How is climate change being taught in American schools? Is it being taught at all? And how are teachers addressing climate change denial in their classrooms, schools, and school districts? Until today's release of NCSE's comprehensive nationwide survey, no one knew.
Categories: Science

Kanye West Is Releasing a Videogame About His Late Mother

Wired News - Thu, 11/02/2016 - 11:24pm

The game, called "Only One," depicts a winged angelic version of the late Donda West soaring through heaven.

The post Kanye West Is Releasing a Videogame About His Late Mother appeared first on WIRED.

Categories: Science

Kim Jong-Un Found To Be Mac User

Slashdot - Thu, 11/02/2016 - 11:21pm
jones_supa writes: He might hate the United States, but he sure digs those designed-in-California computers. You probably wouldn't take Kim Jong-un as a Mac user. Usually, in photos of him checking out military computers, we see the North Korean dictator in front of a PC with a Dell monitor. However, a handful of photos of the supreme leader at his own desk show him with Macs, leading to the assumption that while the military may use PCs, his personal preference is Mac. Reuters correspondent James Pearson, who covers both Koreas, tweeted out a fresh image of little Kim using a MacBook Pro inside an aircraft. There are other images, including a 2013 image of Kim Jong-un at his desk with an iMac. That same year, the South Korean newspaper Chosun published a photo from North Korean Central News Agency, which features an Apple iMac. This might also explain why the country's home-grown Linux distribution Red Star imitates OS X.

Read more of this story at Slashdot.

Categories: Science

Song Exploder: Why the New Pornographers’ ‘Brill Bruisers’ Needed Nonsense

Wired News - Thu, 11/02/2016 - 11:04pm

The frontman of the Canadian supergroup that includes Neko Case and Dan Bejar breaks down the title track from the band's sixth album.

The post Song Exploder: Why the New Pornographers’ ‘Brill Bruisers’ Needed Nonsense appeared first on WIRED.

Categories: Science

Time Inc. Buys MySpace Parent Company Viant

Slashdot - Thu, 11/02/2016 - 10:46pm
Today, in a surprising turn of events, Time Inc. went back in time 10 years and bought MySpace. Just kidding - there was no time travel. But Time did announce today that they acquired Viant, a company that has a large ad tech business, but also owns other properties, including the old networking site MySpace. Terms of the deal have not yet been disclosed, but Time described the acquisition as "game changing," most likely in regards to Viant's ad-tech business. It remains to be seen what this will do for the future of MySpace ...

Read more of this story at Slashdot.

Categories: Science

Our Hidden Neanderthal DNA May Increase Risk of Allergies, Depression

Slashdot - Thu, 11/02/2016 - 10:03pm
sciencehabit writes: Depressed? Your inner Neanderthal may be to blame. Modern humans met and mated with these archaic people in Europe or Asia about 50,000 years ago, and researchers have long suspected that genes picked up in these trysts might be shaping health and well-being today. Now, a study in the current issue of Science details their impact. It uses a powerful new method for scanning the electronic health records of 28,000 Americans to show that some Neanderthal gene variants today can raise the risk of depression, skin lesions, blood clots, and other disorders.

Read more of this story at Slashdot.

Categories: Science

Game of Thrones: Here Are 20 Brand New Images From Season 6

Wired News - Thu, 11/02/2016 - 10:02pm

Lots of clues to what's going to go down on the sixth season of the HBO show in these. Check them out here.

The post Game of Thrones: Here Are 20 Brand New Images From Season 6 appeared first on WIRED.

Categories: Science