Factor X have we finally found the fountain of Youth?

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paperburn1
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Re: Factor X have we finally found the fountain of Youth?

Postby paperburn1 » Sat May 18, 2019 2:51 am

breakthrough it determining cell degreation
https://www.youtube.com/watch?v=9gxogiUvVkk
telomeres and triggers
I am not a nuclear physicist, but play one on the internet.

williatw
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Re: Factor X have we finally found the fountain of Youth?

Postby williatw » Thu May 23, 2019 11:32 am

22May2019

Considering the Experience of Being One of the Last Mortals


Ever-growing lifespans are the result of regular advances in medical science. In 1900 the three leading causes of death in the United States were pneumonia/influenza, tuberculosis, and diarrhoea. Only a century and a bit on, many of the major acute illnesses are tractable. Every month brings striking new medical advances. Increasingly, medical research is shifting from acute conditions such as influenza towards chronic conditions including diabetes and Alzheimer's. Ageing is the ultimate chronic condition, and there seems to be no reason, in principle at least, that would prevent us from discovering a means of halting or reversing ageing itself.

What if that all happens sooner rather than later? But what if it's not soon enough? Imagine that, after a few more breakthroughs, a scientific consensus emerges that we will have conquered illness and ageing by the year 2119; anyone alive in 2119 is likely to live for centuries, even millennia. You and I are very unlikely to make it to 2119. But we are likely to make it relatively close to that date - in fact, relative to the span of human history, we've already made it very close right now. Think that through, carefully. What would it mean to realize that you very nearly got to live forever, but didn't? What would it mean if, in our looming senescence, we were increasingly forced to share social space with young people whose anticipated allotment of time massively dwarfs our own? We would then be the last mortals.


https://www.fightaging.org/archives/201 ... t-mortals/


The comments (some of them) are more interesting than the article they are commenting about:

Sadly and however much life extensionists are loath to admit it, the real doom line isn't chronological age but income, since those who can afford experimental therapies and are cued in enough to know that they exist (education is in itself a marker of wealth) will be able to reduce their yearly risk of death much sooner than the frey. Which means that it's entirely plausible for the odds to LEV of a population of rich 60 (or even 70) year olds to be higher than those of a population of poor 40 year olds.


There's a scary little word at the end of the TLS article, one that isn't as much as whispered in our community even though it nags at the back of everybody's mind. Sabotaging those who have what we crave is a universal, if dark, human response, and we should know better than stoke the fire: my beloved Eternal Youth... if I can't have you, nobody else will.


Posted by: John S at May 22nd, 2019 9:23 PM

To me it doesn't make sense at all to draw the line of doom at 40, which is the conventional beginning of middle age. In fact, it doesn't make much sense to draw it at 60, since as Antonio said a 40 year old woman in Spain is already expected to live to 90. This includes smokers, the obese, couch potatoes etc. so it's reasonable to believe that a clean living woman will reach 95. But wait, I was talking about a 60 year old, which means adding another couple of years to the total since we have already eliminated all the deaths occurring between 40 and 59.

To this intervention-less life expectancy of 97 we can add the 3 years or so (very, very conservative estimate) that will be brought on by a combination of NAD+, metformin, rapamycin, and cancer immunotherapy - just to mention stuff that exists. Plus 5 years from senolytics, if we are being conservative too, for a grand total of 105.

So now we can expect 50% of all 60 year old women in Spain to make it to 2064. Does anyone really believe that in almost half a century we will be stuck with the same therapies of today? SENS is supposed to repair the damage caused by aging, so by then we should have enough first or even second generation treatments not to slow the rate at which these centenatians keep aging, which would be pointless, but to shave off at least 20-30 years from their biological age (= statistical risk of death).

Of course the yearly risk of death of an 80 year old woman is pretty high, so without any additional breakthrough she wouldn't last much longer, and precisely, according to current mortality rates which are a gross underestimate, 11 years. Now it's 2075... at which point there will likely be a bunch of ways to avoid death in addition to cell repair, from mind uploading to reliable suspended animation, via more esoteric stuff like body transplants and robotics.

The usual objection here is that SENS may repair damage comprehensively enough only in those who aren't literally aged to death, which would disqualify our 105 year olds... IF these therapies went from being fantasy in 2063 to hitting the market all at once in 2064, which clearly won't be the case. My point is, the 105 year old women queuing for the latest rejuvenation trearment in 2064 will be biologically younger than any current 105 year old thanks to the cumulative rejuvenating effects of all the post-senolytic therapies that will gradually become available from, say, the mid 2020s onwards.

Sadly and however much life extensionists are loath to admit it, the real doom line isn't chronological age but income, since those who can afford experimental therapies and are cued in enough to know that they exist (education is in itself a marker of wealth) will be able to reduce their yearly risk of death much sooner than the frey. Which means that it's entirely plausible for the odds to LEV of a population of rich 60 (or even 70) year olds to be higher than those of a population of poor 40 year olds.

What I am getting at is that we shouldn't be talking about odds to biological immortality in terms of generations. Firstly because the thinking is flawed, and secondly because it doesn't help our cause given that the vast majority of radical life extension supporters - and those we need the help of - are already middle aged, close to it, or well above.

There's a scary little word at the end of the TLS article, one that isn't as much as whispered in our community even though it nags at the back of everybody's mind. Sabotaging those who have what we crave is a universal, if dark, human response, and we should know better than stoke the fire: my beloved Eternal Youth... if I can't have you, nobody else will.



https://www.fightaging.org/archives/201 ... /#comments


The last mortals may be ghosts before their time, destined to look on in growing envy at the enormous stretches of life left to their near-contemporaries. In one sense, it will be the greatest inequity experienced in all human history.


https://www.the-tls.co.uk/articles/publ ... mortality/

williatw
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Re: Factor X have we finally found the fountain of Youth?

Postby williatw » Tue Jun 04, 2019 8:38 am

Another update from Bill Andrews:


Sierra Sciences LLC

Brent Nally interviews Dr. Bill Andrews @ Sierra Sciences about curing human aging & chronic disease

This video is an interview of Dr. Bill Andrews along with a tour of his company, Sierra Sciences, office on May 30, 2019. My wife, Lauren Nally, was our camerawoman. We had to stop filming for a bathroom break. We also had to keep our voices down during the office tour due to employees working. I believe we can get closer to reversing human aging by finding stronger human telomerase activators if Sierra Sciences receives more funding ($50 million USD would probably be enough for Dr. Andrews and his team to discover stronger human telomerase activators within a year).


https://www.youtube.com/watch?v=Tx9yG6iTROQ

To help the time/patience constrained, the interesting part about the long promised first human trial with his telomerase therapy by Libella is around 56:40. He (Andrews) is now saying it hasn't happen yet but will sometime in June of this year at an overseas location. He alluded again to his selected "patient zero", who is suffering from advanced dementia/Alzheimer. He is saying this treatment is like a more advanced version of the one Liz Parrish received over three years ago.

paperburn1
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Re: Factor X have we finally found the fountain of Youth?

Postby paperburn1 » Tue Jun 04, 2019 6:32 pm

China now claims to have two "Enhanced babies" with a third on the way. At first it was touted that is was just HIV resistance but with the third birth it was also shown intelligence and memory enhancements were part of the package.

Image
I am not a nuclear physicist, but play one on the internet.

williatw
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Re: Factor X have we finally found the fountain of Youth?

Postby williatw » Tue Jun 04, 2019 10:33 pm

paperburn1 wrote:China now claims to have two "Enhanced babies" with a third on the way. At first it was touted that is was just HIV resistance but with the third birth it was also shown intelligence and memory enhancements were part of the package.



China’s CRISPR twins might have had their brains inadvertently enhanced


New research suggests that a controversial gene-editing experiment to make children resistant to HIV may also have enhanced their ability

Image


The brains of two genetically edited girls born in China last year may have been changed in ways that enhance cognition and memory, scientists say.

The twins, called Lulu and Nana, reportedly had their genes modified before birth by a Chinese scientific team using the new editing tool CRISPR. The goal was to make the girls immune to infection by HIV, the virus that causes AIDS.

Now, new research shows that the same alteration introduced into the girls’ DNA, deletion of a gene called CCR5, not only makes mice smarter but also improves human brain recovery after stroke, and could be linked to greater success in school.

“The answer is likely yes, it did affect their brains,” says Alcino J. Silva, a neurobiologist at the University of California, Los Angeles, whose lab uncovered a major new role for the CCR5 gene in memory and the brain’s ability to form new connections.

“The simplest interpretation is that those mutations will probably have an impact on cognitive function in the twins,” says Silva. He says the exact effect on the girls’ cognition is impossible to predict, and “that is why it should not be done.”




https://www.technologyreview.com/s/6129 ... s-altered/


Addendum:

China gene babies' mutation linked to higher mortality: study

The genetic mutation given to Chinese twins last year rendering them immune to the HIV virus may significantly reduce life expectancy, scientists said Monday in a fresh warning against human gene-editing.

He used a gene-editing tool known as Crispr to insert a mutated variant of a CCR5 gene -- known as Delta32 -- into the girls' chromosome at the embryo stage meaning they are now immune to the AIDS-causing HIV virus.

But a new wide-ranging study of genetic make-up and death registry information suggests individuals carrying the D32 mutation face a 20-percent higher risk of early death compared with the global population.
The research, published in the journal Nature Medicine, doesn't explain why the mutation increases mortality risk, but the authors said there was a clear statistical trend that should discourage repeats of He's experiment.


https://www.yahoo.com/news/china-gene-b ... 15160.html

Well if you want to be a "super-soldier" or some such you have to be prepared to face the price; like the fictional "Replicants" in the original Blade runner from 1982 who had had a four year life span. Although in their case it was a deliberately engineered failsafe not an "error".

krenshala
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Re: Factor X have we finally found the fountain of Youth?

Postby krenshala » Thu Jun 06, 2019 5:05 pm

Here's to hoping this is not the official start of what causes the Eugenics Wars (Star Trek), or the battles against the Sauron Supermen (Niven's Known Space).

TDPerk
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Re: Factor X have we finally found the fountain of Youth?

Postby TDPerk » Sat Jun 15, 2019 7:40 pm

williatw wrote:22May2019

Considering the Experience of Being One of the Last Mortals


Ever-growing lifespans are the result of regular advances in medical science. In 1900 the three leading causes of death in the United States were pneumonia/influenza, tuberculosis, and diarrhoea. Only a century and a bit on, many of the major acute illnesses are tractable. Every month brings striking new medical advances. Increasingly, medical research is shifting from acute conditions such as influenza towards chronic conditions including diabetes and Alzheimer's. Ageing is the ultimate chronic condition, and there seems to be no reason, in principle at least, that would prevent us from discovering a means of halting or reversing ageing itself.

What if that all happens sooner rather than later? But what if it's not soon enough? Imagine that, after a few more breakthroughs, a scientific consensus emerges that we will have conquered illness and ageing by the year 2119; anyone alive in 2119 is likely to live for centuries, even millennia. You and I are very unlikely to make it to 2119. But we are likely to make it relatively close to that date - in fact, relative to the span of human history, we've already made it very close right now. Think that through, carefully. What would it mean to realize that you very nearly got to live forever, but didn't? What would it mean if, in our looming senescence, we were increasingly forced to share social space with young people whose anticipated allotment of time massively dwarfs our own? We would then be the last mortals.


https://www.fightaging.org/archives/201 ... t-mortals/


The comments (some of them) are more interesting than the article they are commenting about:

Sadly and however much life extensionists are loath to admit it, the real doom line isn't chronological age but income, since those who can afford experimental therapies and are cued in enough to know that they exist (education is in itself a marker of wealth) will be able to reduce their yearly risk of death much sooner than the frey. Which means that it's entirely plausible for the odds to LEV of a population of rich 60 (or even 70) year olds to be higher than those of a population of poor 40 year olds.


There's a scary little word at the end of the TLS article, one that isn't as much as whispered in our community even though it nags at the back of everybody's mind. Sabotaging those who have what we crave is a universal, if dark, human response, and we should know better than stoke the fire: my beloved Eternal Youth... if I can't have you, nobody else will.


Posted by: John S at May 22nd, 2019 9:23 PM

To me it doesn't make sense at all to draw the line of doom at 40, which is the conventional beginning of middle age. In fact, it doesn't make much sense to draw it at 60, since as Antonio said a 40 year old woman in Spain is already expected to live to 90. This includes smokers, the obese, couch potatoes etc. so it's reasonable to believe that a clean living woman will reach 95. But wait, I was talking about a 60 year old, which means adding another couple of years to the total since we have already eliminated all the deaths occurring between 40 and 59.

To this intervention-less life expectancy of 97 we can add the 3 years or so (very, very conservative estimate) that will be brought on by a combination of NAD+, metformin, rapamycin, and cancer immunotherapy - just to mention stuff that exists. Plus 5 years from senolytics, if we are being conservative too, for a grand total of 105.

So now we can expect 50% of all 60 year old women in Spain to make it to 2064. Does anyone really believe that in almost half a century we will be stuck with the same therapies of today? SENS is supposed to repair the damage caused by aging, so by then we should have enough first or even second generation treatments not to slow the rate at which these centenatians keep aging, which would be pointless, but to shave off at least 20-30 years from their biological age (= statistical risk of death).

Of course the yearly risk of death of an 80 year old woman is pretty high, so without any additional breakthrough she wouldn't last much longer, and precisely, according to current mortality rates which are a gross underestimate, 11 years. Now it's 2075... at which point there will likely be a bunch of ways to avoid death in addition to cell repair, from mind uploading to reliable suspended animation, via more esoteric stuff like body transplants and robotics.

The usual objection here is that SENS may repair damage comprehensively enough only in those who aren't literally aged to death, which would disqualify our 105 year olds... IF these therapies went from being fantasy in 2063 to hitting the market all at once in 2064, which clearly won't be the case. My point is, the 105 year old women queuing for the latest rejuvenation trearment in 2064 will be biologically younger than any current 105 year old thanks to the cumulative rejuvenating effects of all the post-senolytic therapies that will gradually become available from, say, the mid 2020s onwards.

Sadly and however much life extensionists are loath to admit it, the real doom line isn't chronological age but income, since those who can afford experimental therapies and are cued in enough to know that they exist (education is in itself a marker of wealth) will be able to reduce their yearly risk of death much sooner than the frey. Which means that it's entirely plausible for the odds to LEV of a population of rich 60 (or even 70) year olds to be higher than those of a population of poor 40 year olds.

What I am getting at is that we shouldn't be talking about odds to biological immortality in terms of generations. Firstly because the thinking is flawed, and secondly because it doesn't help our cause given that the vast majority of radical life extension supporters - and those we need the help of - are already middle aged, close to it, or well above.

There's a scary little word at the end of the TLS article, one that isn't as much as whispered in our community even though it nags at the back of everybody's mind. Sabotaging those who have what we crave is a universal, if dark, human response, and we should know better than stoke the fire: my beloved Eternal Youth... if I can't have you, nobody else will.



https://www.fightaging.org/archives/201 ... /#comments


The last mortals may be ghosts before their time, destined to look on in growing envy at the enormous stretches of life left to their near-contemporaries. In one sense, it will be the greatest inequity experienced in all human history.


https://www.the-tls.co.uk/articles/publ ... mortality/


" Sabotaging those who have what we crave is a universal, if dark, human response, " <-- It is the hook the Democrats and all Leftists hang their hat on. It is where and how they live.
molon labe
montani semper liberi
para fides paternae patria

kurt9
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Re: Factor X have we finally found the fountain of Youth?

Postby kurt9 » Sat Jun 15, 2019 8:24 pm

Of course. Leftism, as an ideology is not about value creation. It about taking value from those who create it and giving it to those who do not. In other words, its pure parasitism.

Having said that, there are two ways around the problem of not making it due to cost. The first is DIY approaches with various supplements and compounds (senolytics being examples of this) as well as potentially international treatments (stem cells, etc.) that are cheaper than here in the U.S. The second approach is plan "C", "C" meaning cryonics, which can be paid for with life insurance.

Most of us are not rich. I, for one, cannnot afford to shell out $2 million for that gene therapy or for Bill Andrew's telomere elongation therapy. However, there are ways to accomplish this on the cheap.

williatw
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Re: Factor X have we finally found the fountain of Youth?

Postby williatw » Sat Jun 15, 2019 11:34 pm

TDPerk wrote:" Sabotaging those who have what we crave is a universal, if dark, human response, " <-- It is the hook the Democrats and all Leftists hang their hat on. It is where and how they live.



kurt9 wrote:Of course. Leftism, as an ideology is not about value creation. It about taking value from those who create it and giving it to those who do not. In other words, its pure parasitism.


Yes pure politics of envy; if I can't have it why should you? Then all that is needed is for some kind of demagogue type to come along and articulate that feeling with some kind of convincing sounding rhetoric. Something that convinces the target audience that the rich person "stole", "exploited", etc. their wealth/success, therefore it is only "fair", just", etc. for the government to take it away for the "common good".


kurt9 wrote:Most of us are not rich. I, for one, cannnot afford to shell out $2 million for that gene therapy or for Bill Andrew's telomere elongation therapy. However, there are ways to accomplish this on the cheap.


But what about:

williatw wrote:At around 07:41 in the clip he says the treatment would cost around 400K; this is considerably cheaper he says then the 3 million he was saying it would have caused some months ago. According to him they have made great progress in lowering cost; not that much more expensive at this point then what we do now to treat the diseases of aging. How much does cancer/heart disease/Alzheimer’s treatments cost in aggregate over a lifetime now? To say nothing of nursing home care? And you end up dying anyway? Versus 400K to make you young/healthy/continually working tax paying again. And that is even assuming no economies of scale to lower costs further once production is ratcheted up.


viewtopic.php?f=8&t=3504&p=132036&hilit=400K#p132036

He (Bill Andrews) says he has lowered the cost to 400K; that is to the cost of a house kurt9; people arrange that kind of financing all the time. You wouldn't be willing to do the same to not die? Although of course "cost" isn't the same thing as price but still.

While I don't have any figures on Church's "doggie" treatments, I somehow I doubt they are costing "$2 million "; even a rich person might balk at that for their pooch. Although of course it might run considerable more to treat people; unless as it is likely you have to go overseas on some sort of medical holiday/vacation to get it.

williatw
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Re: Factor X have we finally found the fountain of Youth?

Postby williatw » Wed Jul 17, 2019 1:01 pm

Can a Single Pill Keep You Healthy to 100?

New drug being developed and tested that could change the future of aging forever

by Sari Harrar, AARP, July 1, 2019

Image


Drugs like RTB101 work by inhibiting an enzyme in the mTOR pathway, a basic process that regulates growth and metabolism in cells. As we get older, part of this pathway, TORC1, seems to rev up a bit. That's bad. “More TORC1 activity seems to be associated with age-related health problems,” Mannick says. The drugs throttle it back. “It works the same way calorie restriction and intermittent fasting work. In aging studies in animals, cutting back on calories increases life span. But that's difficult for people to do for decades. Inhibiting TORC1 this way seems to do the same thing, without the dieting."


Here it is, the elixir of life!” Joan Mannick says, jokingly, as she drops a shiny, salmon-pink pill into my palm. It’s RTB101, a drug developed by Mannick’s Boston-based biotech company that could change the future of aging forever.

I feel a crazy urge to pop it into my mouth. Similar drugs have extended the lives of countless worms, fruit flies and mice by slowing down an ancient aging process. But unlike most other promising substances that have come and gone, this one has been shown to work in another notable species: humans.

In studies of more than 900 people by Mannick and her team, RTB101 and drugs like it bolstered aging immune systems, cut risk for respiratory diseases and may have lowered the risk of urinary tract infections. A version of the RTB101 drug could win Food and Drug Administration (FDA) approval as early as 2021 for a single, age-related health threat: the winter colds, flu, pneumonia and other respiratory tract infections that send over 1 million older adults to the hospital every year and kill more than 75,000. Studies of the drug as a preventive for Parkinson's disease are set for later this year, with additional research looking into its effect in reducing heart failure being eyed for some time in the future.

In the suddenly hot world of aging science, RTB101 is an A-list celebrity. It's the biggest star in the current quest for a drug that extends the healthy lifespan, a quest aided by the National Institutes of Health's little-known, taxpayer-funded Interventions Testing Program (ITP). The ITP has been quietly experimenting with compounds thought to extend longevity in mice and worms at three major laboratories across the nation. One of the best-kept secrets in aging research, the $4.7 million-a-year ITP has also debunked some big antiaging crazes, including green tea, curcumin and resveratrol.

But RTB101 has shown real promise, as have other similar drugs. An unprecedented number of age-defying compounds from labs across the U.S. are now heading into human clinical trials for the first time.



"We've reached the perfect storm in aging science,” says physician Nir Barzilai, founding director of the Institute for Aging Research at Yeshiva University's Albert Einstein College of Medicine in the Bronx, New York. “Everything is happening. We have the foundation from decades of animal studies. We're ready to move on to people."

The ultimate goal: to put the brakes on aging itself — preventing the pileup of chronic health problems, dementia and frailty that slam most of us late in life. “I want 85 to be the new 65,” says Mannick, the chief medical officer and cofounder of resTORbio, the company developing RTB101.

Not longer life, but better life

The need is enormous. In a decade, nearly 1 in 5 Americans will be 65 or older. Three out of 4 will have two or more serious health conditions. At least 1 in 4 can expect memory lapses and fuzzy thinking, while 1 in 10 will develop dementia.

"Right now doctors play whack-a-mole with chronic diseases in older adults. You treat one, another pops up,” says Felipe Sierra, director of the National Institute on Aging's Division of Aging Biology. “The goal instead is to tackle aging itself, the major risk factor for almost every major disease."

While these drugs might also extend longevity, experts say that's a side effect, not the real goal. “People don't want to live longer,” notes S. Jay Olshansky, a professor of public health and a researcher on aging at the University of Chicago. “They want to stay out of the red zone — the years when health and quality of life decline drastically. A drug that slows the biological process of aging will be a medical revolution on par with the discovery of antibiotics. Whoever develops the first one will be very, very famous."

It's no wonder, then, that Mannick says, “I stayed up all night at my kitchen table, with a piece of paper, a pencil and the raw data” when she ran a 2012 study widely regarded as the first human aging trial. The results were thrilling. Older people
who took RAD001, a similar drug to RTB101, had a stronger response to a flu vaccine. Their immune systems looked younger, with fewer exhausted T cells — a depressingly common feature of aging called immunosenescence. “This was the first evidence that if you target a pathway in humans, you may actually impact how we age."

Slender and dressed casually in a cotton skirt, tights and flats, Mannick tells me she's turning 60 soon. She views her own aging with cheery wonder. “I look in the mirror and think, Wow! My body is completely different now! It's kind of cool,” she says, chopping the air with her hands to emphasize her point.

ImageJoan Mannick in her Boston office


“If I can live long enough to meet my great-grandchildren and great-great-grandchildren and be healthy, I'd love to do it.”
- Joan Mannick, developer of the drug RTB101





An infectious disease specialist with a Harvard Medical School degree, she walks fast on a treadmill every day and generally follows a healthy diet — a habit fostered by her nutrition-conscious mom. Indeed, her personal passion for the science of aging grew as she watched her parents age. “They were raised in similar kinds of families in the Midwest and West. Both were college athletes, both went to Harvard Medical School and lived in the same environment for the decades of their marriage,” she says.

"But they have aged completely differently. Both are 90. My dad is robust and energetic. My mother is frail and has dementia. Our society, our drug companies and medical profession aren't addressing all this suffering that happens as people grow old. But the older people in my life are beloved to me. If we can do something about aging, we shouldn't ignore it."

In the winter of 2015, Ken Butterfield, 67, took a small pill every morning as part of a clinical trial run by resTORbio. The study tested the effects of several doses of RTB101, some mixed with a second drug, on respiratory infections in 652 adults 65 and older.

"I don't like getting sick,” says this retired mental health caseworker and commercial refrigeration installer from upstate New York. “The possibility of fewer winter colds was a selling point for me.” Swallowing an experimental drug didn't worry him. “I've been in clinical trials before, so I felt safe,” he adds. “My first was a smallpox vaccine booster study right after 9/11. There was a smallpox scare. I was too old to fight in the military and wanted to help people."

Butterfield and resTORbio don't know whether he took RTB101 or a placebo; the results are “blinded,” to curb bias. Statistically, though, those who took 10 milligrams of RTB101 daily had 31 percent fewer respiratory infections — including colds, flu, bronchitis and pneumonia. There were 52 percent fewer severe infections, too. Those with asthma fared even better, with 68 percent fewer infections. “Their antiviral defenses were turned up,” Mannick says.

The results were particularly strong for people 85 and older; they had 67 percent fewer infections. That's good news, because — in part due to an age-related weakening of the immune system — respiratory infections are the fourth-leading reason older U.S. adults wind up in the hospital and their eighth-leading cause of death. “The results show that RTB101 translates to fewer infections,” Mannick notes.

Firsthand experience with the woes of winter colds and flu may be why volunteers signed up for the respiratory infection study in record time. “When I told my mom about the study, she said she'd give anything not to get a cold every winter,” says physician Kerry Russell, vice president of clinical development at resTORbio.


“I don't like getting sick. The possibility of fewer winter colds was a selling point for me.”
- Ken Butterfield, trial participant

Some volunteers went overboard. In New Zealand, where part of one study took place, men from a recreational rugby club signed up together. That study, which measured the effect of a drug like RAD001 on the immune system, also kept tabs on other signs of health and fitness, such as changes in walking speed. “They'd have their checkups together and then go out for a pint,” Mannick says. “But they turned the walking-speed check into a competition, which totally threw off those results. We learned to stop giving people those numbers."

Other checks included electrocardiograms before and after, and tests of hand strength. “We're looking for signals that may be worth studying in the future, such as heart function and muscle strength,” Mannick explains. (ResTORbio is still reviewing the data.) Meanwhile, the company recently launched a phase 3 study of RTB101 for immunity and prevention of respiratory infections in hundreds of older adults, designed in consultation with the FDA. If the drug is successful, it could be approved for those uses as early as 2021.

A separate clinical trial in people with and without GBA-associated Parkinson's disease (which results from a mutation of the GBA1 gene) is set to begin this year as well, according to Russell. “At first we'll look at safety and whether the drug crosses the blood-brain barrier,” she says. “If that's successful, later studies will look at whether RTB101 has an effect on Parkinson's symptoms and on the progression of the disease in the brain."

Common side effects so far are diarrhea and headache. But in the respiratory tract infections study, more people in the placebo group had side effects than did those who took the drug.

A drug such as RTB101 could start out as a boutique antidote aimed at a couple of age-related problems, not all of aging. “That could happen if the same dose helps several conditions, but you'd need individual studies, which could take months or years, first,” say Mannick.
Keeping cells young

How does RTB101 circumvent aging? We've arrived at the part of the story that reads like a scientific detective novel — a tale with some remarkable thrills and chills.

Drugs like RTB101 work by inhibiting an enzyme in the mTOR pathway, a basic process that regulates growth and metabolism in cells. As we get older, part of this pathway, TORC1, seems to rev up a bit. That's bad. “More TORC1 activity seems to be associated with age-related health problems,” Mannick says. The drugs throttle it back. “It works the same way calorie restriction and intermittent fasting work. In aging studies in animals, cutting back on calories increases life span. But that's difficult for people to do for decades. Inhibiting TORC1 this way seems to do the same thing, without the dieting."

Scientists discovered mTOR while studying rapamycin, a drug that is used today to prevent rejection in some organ transplants and cancer. In fact, mTOR is short for “mammalian target of rapamycin.” But rapamycin almost landed in a pharmaceutical-company trash can in the 1980s.

First discovered seeping from bacteria scraped up on Easter Island, it showed promise as a remedy for yeast infections. When a Canadian drug company halted its development (because it negatively affected immunity), an enterprising scientist stashed the last research vials at home in his freezer, beside the ice cream. His devotion paid off. A few years later, rapamycin was brought back into research and became the antirejection drug sirolimus and the cancer drug everolimus.

Along the way, scientists realized rapamycin “didn't really look like any other drug,” one researcher recalled. “Its pattern of activity was unique.” One weird trick: This Easter Island ooze made fruit flies, worms and yeast cells live longer.

Could it help humans? The Interventions Testing Program looked for clues in a mammal surprisingly like us: the mouse. Testing the drug for this new usage was a big step. The ITP is high powered, rigorous and brutally honest. Launched in 2003, it tests potential age-defying compounds in extremely strict mouse studies at the University of Michigan; the Jackson Laboratory in Bar Harbor, Maine; and the University of Texas Health Science Center in San Antonio. Richard Miller, professor of pathology and director of the Glenn Center for Aging Research at the University of Michigan Medical School, runs one of the labs.

"We are rigorous about making sure the conditions are exactly the same at all three labs: the same food, the same water, the same lab temperatures, the same training for lab technicians,” Miller says. “The doors are kept locked; only people working on the study can enter. The goal is to be sure mouse longevity-study results are reproducible. So often in the past, an exciting study in one lab could never be repeated anywhere else. We're also notable because we publish all of our results, whether a compound extends longevity or not.” So far, only a few compounds have shown promise — with rapamycin the strongest.

In 2007, the ITP tested rapamycin in hundreds of mice. The results: Old mice (equivalent to 60-year-old people) who got rapamycin lived longer (28 percent for males and 38 percent for females), according to a 2009 study in the journal Nature. “It's one of the most exciting interventions we have,” says David Harrison of the Jackson Laboratory, which participates in the ITP. “It works at any age in mice, and that makes it interesting.” In other studies, mice on rapamycin were healthier, leaner and stronger into their rodent golden years.

Mannick read all this research and more. And the pattern was clear. In mice, yeast, worms and flies, you could extend life span and improve health by inhibiting the mTOR pathway. “That made me think, Someone has to test this in humans,” she says.

Attacking the “zombie cells"

Alas, there's more going wrong in older cells than on-the-fritz mTOR. “We've identified several major pillars of aging,” says Sierra, of the National Institute on Aging. The list reads like the plagues of the Old Testament. Among them: inflammation; out-of-whack metabolism; inactive stem cells that can't repair body tissues; damage from stress, environmental toxins and free radicals; reduced “quality control,” which can't eliminate rogue cells. These glitches boost the risk for everything from heart disease and stroke to diabetes, osteoarthritis, Alzheimer's disease, Parkinson's and cancer.

This is an important point. If these and other cellular issues are the underlying causes of so many diseases, preventing cells from succumbing to them as they age is a key to preventing disease. That's why resTORbio, other biotech start-ups and university aging labs across the U.S. are launching an unprecedented number of human clinical trials with experimental compounds aimed at these pillars.

"It's a cautious period,” says physician James Kirkland, director of the Mayo Clinic's Kogod Center on Aging in Rochester, Minnesota. “Exciting findings in mice often don't turn out so well in people. It's impossible to predict what the human trials will show."

One big target: “zombie cells” — aging, or “senescent,” cells that refuse to die, instead glomming up in joints and other body tissues. They pump out dozens of inflammatory compounds and other chemicals that contribute to osteoarthritis, Alzheimer's, glaucoma, high blood pressure, type 2 diabetes, disk degeneration in the spine, lung problems and more. In a raft of mouse studies, clearing out these senescent cells boosted health — easing arthritis pain, improving kidney and lung function, increasing fitness, extending life and even making fur thicker.

In January, the first-ever human study of a treatment to kill senescent cells in the lungs was published, in the journal EBioMedicine. Fourteen people with the fatal lung disease idiopathic pulmonary fibrosis took a mix of the drugs dasatinib and quercetin for three weeks. The verdict: The drug combo was safe, triggered just one serious side effect (pneumonia), and seemed to improve study volunteers’ basic ability to stand up and walk. There were also hints it may have reduced senescent-cell activity, but the researchers say bigger, longer studies are needed.

In the meantime, Kirkland says, human trials of other zombie slayers are underway in “a number of groups around the world, including several at the Mayo Clinic.” In June 2018, Unity Biotechnology of San Francisco began its first human trial injecting UBX101, a senolytic (that is, a drug that kills senescent cells), into the achy knees of 40 people, ages 40 to 85, with moderate to severe osteoarthritis.

Kirkland and others at the Mayo Clinic are also paying attention to potential senolytics such as fisetin, which is found in fruits and vegetables. In a planned study, researchers will give fisetin to 40 women ages 70 to 90 to see if it helps them walk faster and become more active. Plus, researchers will look at the effects on bone density, inflammation, blood sugar processing and frailty. “I don't want to say a lot about these studies now,” Kirkland adds. “Some are in compounds that people can buy as supplements, and I'm very worried about people self-medicating. To get to the amounts in our study, you'd have to eat 15 pounds of strawberries in two minutes. Taking unproven supplements just isn't safe."

On another front, a small human study recently tested the effects of NMN (nicotinamide mononucleotide), a chemical that in a 2013 Harvard study revitalized mitochondria — the power plants inside cells — in aging mice. In a 2018 lab study, it improved blood vessel growth and exercise endurance in mice, too. NMN raises levels of NAD, the compound that seems to help mitochondria work better. Lead researcher David Sinclair, a professor of genetics at Harvard Medical School and codirector of the school's Paul F. Glenn Center for the Biological Mechanisms of Aging, began studying NMN in people last year. “The approach stimulates blood vessel growth and boosts stamina and endurance in mice, and sets the stage for therapies in humans to address the spectrum of diseases that arise from vascular aging,” he says.

There are other promising aging-research fronts. For example, a six-year study of the generic diabetes drug metformin in 3,000 older nondiabetic adults will likely begin this year, notes Barzilai of the Institute for Aging Research. “We have already seen that people who take metformin for type 2 diabetes have less cardiovascular disease, less cancer, less cognitive decline and live longer than people without diabetes,” he points out. “Now we want to test it in people without diabetes."

Metformin may delay problems such as heart disease by two to three years. “It's a weak aging drug, but it will let us study aging itself instead of individual age-related diseases. That will be a first,” Barzilai says. “We've been talking with the FDA about it. Nobody wants to ever call aging itself a disease. We just want to keep people healthier."



Winning the life span lottery

Right now, simply staying healthy into our 80s, 90s and beyond is a lot like hitting the Powerball jackpot. In a survey of 55,000 Americans age 65-plus, just 48 percent rated their health as very good or excellent. No wonder drugstores, the internet and human history are littered with unproven rejuvenation come-ons such as the Fountain of Youth in the 1500s and goat-testicle implants (yikes!) in the Roaring ‘20s. Today's questionable offerings range from stem cells, growth hormones and transfusions of teenage plasma, to supplements and more. In 2017, Americans spent $194 billion on products and treatments like these. This is why serious aging-science researchers steer clear of the word “antiaging” when talking about their work. “ ‘Antiaging’ is my enemy,” Barzilai adds. “Some of those charlatans hurt our reputation."

Meanwhile, as researchers slowly test these more legitimate drugs, what can we do today if we wish to retain good health longer? That answer has been with us all along. “Not smoking, eating healthy, getting exercise, managing stress and sleep,” says physician Thomas Perls, founding director of the New England Centenarian Study. Those steps can keep you healthier into your 90s. You'll have to wait for an aging drug, or inherit lucky genes, to go further. “Centenarians seem to have groups of genes that delay age-related diseases."

More than offering longevity, age-defying drugs may help us escape the red zone — the time when physical health often crashes late in life. “We think future drugs that target aging will go beyond what a healthy lifestyle can do,” says Olshansky, of the University of Chicago. How much longer we can live is unknown. “The outside of normal human aging is about 115, while the average life span is about 80 or 85, so I think we have about 30 extra years to think about,” Barzilai says.

Just feeling 65 at 85 could be a seismic shift. “If I can live long enough to meet my great-grandchildren and great-great-grandchildren and be healthy, I'd love to do it,” Mannick says.

Daniel Callahan, of the Hastings Center for Bioethics in Garrison, New York, explains that it's a balance. “I've never been an enthusiast for longevity for longevity's sake,” he notes. “We would see a great imbalance between the young and the old. One of my main objections to radical life extension is that proponents haven't answered the question, ‘What would life be like?’ On the other hand, I am now 88. Improving aging really means finding ways to prevent cancer, heart disease, stroke. Health is what matters."

At 87, Doris Overton of Austin, Texas, agrees. A retired nurse with three children and five grandchildren, she participated in resTORbio's RTB101 respiratory-infection study several winters ago. “I get bronchitis every winter, and it takes so long to get better,” she says. “If a drug like that can help, it would be a really good thing."

Sari Harrar has authored or coauthored 15 health books and contributes frequently to AARP The Magazine.





https://www.aarp.org/health/drugs-suppl ... aging.html

kurt9
Posts: 557
Joined: Mon Oct 15, 2007 4:14 pm
Location: Portland, Oregon, USA

Re: Factor X have we finally found the fountain of Youth?

Postby kurt9 » Wed Jul 17, 2019 3:34 pm

I don't know about the compound mentioned in the article. I just read elsewhere it's an mTOR thing, like Rapamycin. I think this is one of the weaker pathways to life extension. Senolytics is better. I have tried two senolytic rounds to varying effect. I can tell you the advances are (finally) starting to come fast and furious. There is now enough stuff out there to do serious DIY work.

I stand by what I have said in the past. I am convinced the most of aging (maybe all of it?) is due to mitochondrial dysfunction. Whether this is due to mtDNA damage itself or due to an asymmetry between mitophagy and mt biogenesis is still unclear. The point is that there is stuff NOW that I can do to help remediate this damage. I am currently doing chelation with ALA (alpha lipoic acid) that I will finish at the end of the year. It will be early next year (Jan-Feb) that I will try one of the mitophagy/biogenesis protocols. There is also a senolytics with stem cell replacement protocol that I will try next year as well.

Daniel Callahan is a jack-ass.

One of my main objections to radical life extension is that proponents haven't answered the question, ‘What would life be like?’


This is a dumb-ass question because life is whatever you choose to make ot it. So its stupid to even ask this question and to postulate it as a legitimate argument against radical life extension. My approach is more direct. I seek to secure my long term future first. Then I will have the time and freedom to pursue the truly long-term personal objectives I want to pursue with my life. The point is that I seek to eliminate the barriers to my future personal life before I make any other considerations. Why I would want to invert this process is completely unfathomable to me.

williatw
Posts: 1805
Joined: Mon Oct 12, 2009 7:15 pm
Location: Ohio

Re: Factor X have we finally found the fountain of Youth?

Postby williatw » Thu Jul 18, 2019 10:16 am

kurt9 wrote:I don't know about the compound mentioned in the article. I just read elsewhere it's an mTOR thing, like Rapamycin. I think this is one of the weaker pathways to life extension. Senolytics is better. I have tried two senolytic rounds to varying effect. I can tell you the advances are (finally) starting to come fast and furious. There is now enough stuff out there to do serious DIY work.



The salient point "kurt9" is that longevity treatments are at long last getting significant cred. That is we are rapidly putting a stake through the heart of the label "snake-oil"; once any treatment shows real world efficacy we are well on our way of winning the battle of public belief. No one expects that the first generation treatments like senolytics or compounds to imitate the effects of fasting are the fountain of youth, they are obviously the low hanging fruit producing comparatively modest (but positive) results. A five to fifteen year increase in life expectancy is huge in relative terms; (by comparison curing cancer would increase it by about 4yrs and even curing heart disease about 13 yrs.) First generation treatments like Metformin combined with Rapamycin therapies would probably do that much or more. Their are billions of dollars in venture capital waiting in the wings once sufficient critical mass of acceptance of the concept of aging as a treatable/curable disease takes hold.


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