Scientists find class of drugs that boosts healthy lifespan

Mayo Clinic and collaborators find new class of drugs that reduces aging in mice

A research team from The Scripps Research Institute (TSRI), Mayo Clinic and other institutions has identified a new class of drugs that in animal models dramatically slows the aging process—alleviating symptoms of frailty, improving cardiac function and extending a healthy lifespan.

The new research was published March 9 online ahead of print by the journal Aging Cell.

The scientists coined the term "senolytics" for the new class of drugs.

"We view this study as a big, first step toward developing treatments that can be given safely to patients to extend healthspan or to treat age-related diseases and disorders," said TSRI Professor Paul Robbins, PhD, who with Associate Professor Laura Niedernhofer, MD, PhD, led the research efforts for the paper at Scripps Florida. "When senolytic agents, like the combination we identified, are used clinically, the results could be transformative."

"The prototypes of these senolytic agents have more than proven their ability to alleviate multiple characteristics associated with aging," said Mayo Clinic Professor James Kirkland, MD, PhD, senior author of the new study. "It may eventually become feasible to delay, prevent, alleviate or even reverse multiple chronic diseases and disabilities as a group, instead of just one at a time."

Finding the Target

Senescent cells—cells that have stopped dividing—accumulate with age and accelerate the . Since the "healthspan" (time free of disease) in mice is enhanced by killing off these cells, the scientists reasoned that finding treatments that accomplish this in humans could have tremendous potential.

The scientists were faced with the question, though, of how to identify and target senescent cells without damaging other cells.

The team suspected that senescent cells' resistance to death by stress and damage could provide a clue. Indeed, using transcript analysis, the researchers found that, like cancer cells, senescent cells have increased expression of "pro-survival networks" that help them resist apoptosis or programmed cell death. This finding provided key criteria to search for potential candidates.

Using these criteria, the team homed in on two available compounds—the cancer drug dasatinib (sold under the trade name Sprycel) and quercetin, a natural compound sold as a supplement that acts as an antihistamine and anti-inflammatory.

Further testing in cell culture showed these compounds do indeed selectively induce death of . The two compounds had different strong points. Dasatinib eliminated senescent human fat cell progenitors, while quercetin was more effective against senescent human endothelial cells and mouse bone marrow stem cells. A combination of the two was most effective overall.

Remarkable Results

Next, the team looked at how these drugs affected health and aging in mice.

"In animal models, the compounds improved cardiovascular function and exercise endurance, reduced osteoporosis and frailty, and extended healthspan," said Niedernhofer, whose animal models of accelerated aging were used extensively in the study. "Remarkably, in some cases, these drugs did so with only a single course of treatment."

In old mice, cardiovascular function was improved within five days of a single dose of the drugs. A single dose of a combination of the drugs led to improved exercise capacity in animals weakened by radiation therapy used for cancer. The effect lasted for at least seven months following treatment with the drugs. Periodic drug administration of mice with accelerated aging extended the healthspan in the animals, delaying age-related symptoms, spine degeneration and osteoporosis.

The authors caution that more testing is needed before use in humans. They also note both drugs in the study have possible side effects, at least with long-term treatment.

The researchers, however, remain upbeat about their findings' potential. "Senescence is involved in a number of diseases and pathologies so there could be any number of applications for these and similar compounds," Robbins said. "Also, we anticipate that treatment with senolytic drugs to clear damaged cells would be infrequent, reducing the chance of side effects."


Explore further

Senescent cells play an essential role in wound healing

More information: "Achilles' Heel of Senescent Cells: From Transcriptome to Senolytic Drugs," Aging Cell, 2015. onlinelibrary.wiley.com/doi/10 … /acel.12344/abstract
Journal information: Aging Cell

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Mar 09, 2015
more snake oil.

Mar 09, 2015
"In old mice, cardiovascular function was improved within five days of a single dose of the drugs."

Look at it this way, it should be easy to test and it is inexpensive assuming it also works at a single dose level in humans. The cost of dasatinib (Sprycel) ranges from $137 to $151 per day.

Mar 10, 2015
Quercetin is cheap, natural, and is available OTC. 250mg twice daily is a good dose. If you go any higher, you risk tilting the balance in favor of its bad side effect of topoisomerase II inhibition which can cause secondary cancers; see https://www.ncbi....16950806

Mar 11, 2015
A pre-released version of the full article is available online at:
http://onlinelibr...2344/pdf

One trial in the study used a one-time dose 50 mg of quercetin per kg of body mass.
For an 80-kilo mouse that would be 4 grams, but mice can often handle more per kg than humans due to a faster metabolism, so for an 80-kilo human even a one-time dose should be considerably less than that until relative sensitivity is determined.

@SD: Sounds about right for a daily dose.
With a one-time dose the topoisomerase II inhibition should be less of an issue, so a one-time dose higher than that is probably safe.

I think I'll try a one-gram one-time dose of 1.5 grams on myself and see what happens.
(If no further posts occur, be forewarned that such a dose might be too high!)

Mar 11, 2015
Very interesting. I'm still young enough that I can wait a while to for more research on this.

@RealScience: I'll be checking this blog to see if you quit posting. Please let us know if it's working.

Mar 12, 2015
@RealScience, quercetin is proven to have numerous benefits, so it does make sense for me to take some daily. People with allergies often take it at 1g daily, and they have no complaints. This particular article changes nothing for me. It would however be interesting if I could get my hands on dasatinib once every few months, but of course it's not trivial to get.

Mar 12, 2015
@Shakescene 21: I will post.

@SuejDog: Obtained Quercetin today, but it is EMIQ which claims much higher bioavailability so I'm only trying 1 gram.

Trial notes:
Volunteers: 1
Brand: Natural Factors:
Dose: Twenty capsules each with 50 mg Quercetin as 167 mg of high-bioavailability EMIQ.
Label claims reaches peak levels in bloodstream in 15 minutes.
(However it is thought that metabolites of quercetin may be the most active, and these would peak later)

Day zero = 2012-03-12
Hour 0:
Resting pulse: 59
Dose consumed shortly after eating lasagna.
Subjective reaction: No changer except pool of cold water in stomach.

Hour 0.75-1.0:
Subjective reaction: Several large burps.



Mar 12, 2015
Trial Notes:

Hour 3: Resting pulse 56
Some ache in or near left kidney, but may just be from sitting too long.

Hour 4: Ate dinner, all seems normal

Hour 5: A very slight headache

Hour 6: All seems normal, resting pulse 62

Switching to once-a-day notes unless anything seems unusual.

Mar 13, 2015
Notes: Didn't fall asleep until 3 AM.
While this could be from the anti-soporific effects of antioxidants, the 'control group' (my wife, who is waiting to see if I croak before she chows down on a handful of quercetin capsules) was also awake until 3 AM so it is probably NOT quercetin-related).
Woke up at normal time.

Hour 18: Resting pulse 55
All seems normal.

Hour 21: Some ache near kidneys on both sides (again after lengthy sitting)

Hour 24: Resting pulse 67
All seems normal except pulse a bit fast.

Mar 14, 2015
Ren is right about The Aten.

All others are copiers.

Mar 14, 2015
Jeez I dont know he looks pretty old. He should try it out and do a new vid in 6 months.

Quercetin is hard on the stomach.
Clean nature boost healthy lifespan
So does prayer and a strictly religious life. Except for when it doesnt work, in which case you know you werent doing it right and its your fault.

Mar 14, 2015
Trial Notes, Hour 48:
Resting Pulse 61.
Slept normally last night.

All seems normal except that urine is a bit darker today than usual.

Mar 15, 2015
Trial Notes, Hour 72:
Resting Pulse 65.

All seems normal except that urine is still a bit darker than usual.

Mar 16, 2015
Trial Notes, Hour 96:
Resting pulse 66.

Most things seem normal, but my sense of smell seems to have gotten more sensitive over the past 24 hours.
My resting pulse is also still a bit higher than usual.

Mar 17, 2015
Trail notes, hour 120.
Resting pulse 67 (10% higher than baseline).
Urine is also back to normal.
Still noticing heightened sense of smell.

Also noticed thousands of tiny 'floaters' in vision last night (the clear kind, not black specs), but small enough not to interfere with vision.
By this afternoon most of them were already gone.

The article says that the effect on senescent cells occurred within 5 days, so this is my last daily report.
I'll post again in a week or so if I notice anything else.

Mar 18, 2015
This comment has been removed by a moderator.

Apr 04, 2015
Trial notes, roughly 3 weeks.
Resting pulse back to normal (58 +/-3).
Heightened sense of smell remains, also sense of taste.

When I didn't croak by nine days, my wife also tried a gram of high bioavailabilty EMIQ.
Her results match mine - slight headache, followed by mild kidney ache and stronger urine, and finally a heightened sense of smell and taste.

One other probable result - we both have developed a craving for meat since a few days after the quercetin. Together with the heightened sense of taste, this has made chowing down on steaks with mushrooms and onions very enjoyable.

A sample of two is still not a great basis for drawing conclusions, but since we tried the quercetin at different times and had very similar trajectories it provides a reasonable data point.

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