Factor X have we finally found the fountain of Youth?

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

Postby kurt9 » Sun Aug 11, 2019 2:25 am

That's the point. The epigenetic changes are clearly the cause of all of the aging based dysfunction. That's why if someone comes up with a workable cellular reprogramming protocol that both works and is safe, I will most certainly do it. In the meantime, there is mitochondrial related stuff as well as senolytics that I will do starting early next year.

If nuclear DNA really is a cause of aging, there's a fix for that in the form of a CRISPR therapy that is targeted specific to stem cells that was just developed by Harvard. I think it is also this same thing that George Church used to rejuvenate his lab rats a few months ago.

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

Postby williatw » Sun Aug 11, 2019 2:58 am

kurt9 wrote:That's the point. The epigenetic changes are clearly the cause of all of the aging based dysfunction. That's why if someone comes up with a workable cellular reprogramming protocol that both works and is safe, I will most certainly do it. In the meantime, there is mitochondrial related stuff as well as senolytics that I will do starting early next year.


There could be the programmed "epigenetic changes" causing "aging based dysfunction" and also in addition accumulating damage as a result of simply living. Drinking, smoking, breathing polluted air, other contaminates in the environment from food/drink etc. Even if our repair mechanism(s) didn't degrade as a result of epigenetic changes there would still be cumulative damage from that. Merely the fact that we need oxygen to process our food generates free radicals that yes damage us over time even with repair mechanism functioning at the "youthful" level. I am not as ambitious (brave) as you are; my current regime is notable for Elysium Basis (recently) and Longevinex for many years; the later recently added Fisetin to it's ingredients list probably in too low a concentration. Very recently added Berberine to my mix as a substitute for Metformin requiring a prescription. Stem cell therapies are an interest of mine as well but haven't been bold enough (or rich enough) to take advantage of them yet. I have diagnosed arthritis in my left shoulder with accompanying bone spurs. Understand famously that Mel Gibson's then 92 yr old Dad received stem cell therapy for a host of issues with apparently (continuing) good results several years ago.

Host Michael Beattie discusses stem cell therapy using *human umbilical cord tissue-derived mesenchymal stem cells (hUCT-MSCs) at the Stem Cell Institute in Panama with renowned applied stem cell scientist and founder, Neil Riordan, Pa, PhD and acclaimed actor, director and producer Mel Gibson.

Dr. Riordan discusses the miraculous progress of a spinal cord injury patient and pilot whose doctors said that he would never walk again. He talks about where the stem cells come from, how they work and why they can treat so many seemingly different conditions. Dr. Riordan explains how umbilical cords, and subsequently, hUCT-MSCs used at the Stem Cell Institute are carefully selected using molecular screening. He also discusses why mesenchymal stem cells from umbilical cords function better than MSCs from adults, especially as they age or if they are suffering from a disease like multiple sclerosis. For example. MSCs from a newborn multiply exponentially compared to MSCs from an older adult.

Mel Gibson discusses his father’s miraculous recovery, literally from his deathbed after receiving hUCT-MSCs at the age of 92. He’s currently 99 and still going strong having been treated in Panama several times since then. Mel also discusses his personal experiences in Panama.


ADDENDUM; More details on Riordan's treatment regime and facility:


Stem Cells: Their Role in Aging and in the Treatment of Chronic Diseases - Neil Riordan, PA, PhD.

Published on May 16, 2019


Dr. Riordan discusses stem cell therapy at the Stem Cell Institute in Panama City, Panama. He mentions the two main types of adult stem cells but his talk focuses on mesenchymal stem cells including their sources and functions. Then he goes on to discuss specifically the specially selected human umbilical cord tissue-derived MSCs used in Panama. He highlights several clinical trials for spinal cord injury, rheumatoid arthritis, diabetes and cancer inhibition. He shows MSCs growing in culture and discusses 3D culturing. He then goes into cord tissue products being offered in the US including Signature Cord, which he developed. Finally, Dr. Riordan discusses current US law and the new stem cell law in Texas, including where he sees the industry in the US going from here.


http://www.cellmedicine.com

https://www.youtube.com/watch?v=f9O3Lyz8qw0

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

Postby williatw » Sun Aug 25, 2019 6:44 pm

More about Neil Riordan:

What I've Learned From Neil Riordan And Why I Still Go to Panama For Stem Cell Treatment





Published on Sep 2, 2018


Dr. Riordan is the founder of the Stem Cell Institute in Panama. His clinic was where I first went in October 2008 for treatment that I hoped would help the debilitation and immobility my progressive MS had caused. This man's revolutionary regenerative medical approach changed my life! iLoveMyNewStemCells because all that I have continued to learn during my own stem cell journey. Loved this interview and thought others may benefit from hearing more too ...


https://www.youtube.com/watch?v=73nGjpfqRdk

kurt9
Posts: 564
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Re: Factor X have we finally found the fountain of Youth?

Postby kurt9 » Mon Aug 26, 2019 3:46 pm

The best stem cell therapies are without the stem cells (e.g. cellular reprogramming). That's why its better to wait another 5 years, if possible, rather than doing stem cell treatments that may or may not work.

williatw
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Location: Ohio

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

Postby williatw » Sat Sep 07, 2019 7:47 pm

Brent Nally interviews Dr. Aubrey de Grey @ SENS on July 17, 2019

Published on Jul 18, 2019


My mission is to drastically improve your life by helping you break bad habits, build and keep new healthy habits to make you the best version of yourself. I read the books and do all the research and share my findings with you!

This video is an interview of Dr. Aubrey de Grey @ SENS on July 17, 2019. My wife, Lauren Nally, was our camerawoman.



https://www.youtube.com/watch?v=TquJyz7tGfk

Rather long interview of Dr. Aubrey de Grey; rather interesting note, at about 13:30 minutes in the interviewer makes reference to the long awaited Bill Andrews' telomerase therapy's "patient zero". He (the interviewer) made reference to a conversation he had with Liz Parrish where she indicated said patient who is said to have late stage Alzheimer's, had finally received the telomerase therapy



ADDENDUM: In response to a posted question:

"Thanks for the interview Brent Nally. At about 13:30 you make reference to Bill Andrews' long awaited telomerase therapy patient. Any idea when Andrews will have something to say about progress/results of the treatments?"

Reply:


"I’ll be at RAADfest October 3-6th 2019 in Las Vegas with Dr. Aubrey de Grey, Dr. Bill Andrews, Liz Parrish and many other longevity experts. I’ll ask Bill & Liz for an update on the telomerase gene therapy patient who has Alzheimer’s. This private patient with Alzheimer’s was the second publicly known person (Liz was the first) to receive this telomerase gene therapy. Stay subscribed to my YouTube channel for this update."


In one of the previous interviews I recall Bill Andrews said himself that he didn't regard Liz Parrish's treatment (which he indicated that he was not directly associated with) to be as comprehensive as the one he was going to do on this patient.

williatw
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Location: Ohio

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

Postby williatw » Sun Sep 08, 2019 10:41 am

NEWS · 05 September 2019


First hint that body’s ‘biological age’ can be reversed

In a small trial, drugs seemed to rejuvenate the body’s ‘epigenetic clock’, which tracks a person’s biological age.


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A person’s biological age, measured by the epigenetic clock, can lag behind or exceed their chronological ageCredit: Patrick McDermott/Getty

A small clinical study in California has suggested for the first time that it might be possible to reverse the body’s epigenetic clock, which measures a person’s biological age.

For one year, nine healthy volunteers took a cocktail of three common drugs — growth hormone and two diabetes medications — and on average shed 2.5 years of their biological ages, measured by analysing marks on a person’s genomes. The participants’ immune systems also showed signs of rejuvenation.

The results were a surprise even to the trial organizers — but researchers caution that the findings are preliminary because the trial was small and did not include a control arm.

“I’d expected to see slowing down of the clock, but not a reversal,” says geneticist Steve Horvath at the University of California, Los Angeles, who conducted the epigenetic analysis. “That felt kind of futuristic.” The findings were published on 5 September in Aging Cell.

“It may be that there is an effect,” says cell biologist Wolfgang Wagner at the University of Aachen in Germany. “But the results are not rock solid because the study is very small and not well controlled.”

Marks of life

The epigenetic clock relies on the body’s epigenome, which comprises chemical modifications, such as methyl groups, that tag DNA. The pattern of these tags changes during the course of life, and tracks a person’s biological age, which can lag behind or exceed chronological age.

Scientists construct epigenetic clocks by selecting sets of DNA-methylation sites across the genome. In the past few years, Horvath — a pioneer in epigenetic-clock research — has developed some of the most accurate ones.

The latest trial was designed mainly to test whether growth hormone could be used safely in humans to restore tissue in the thymus gland. The gland, which is in the chest between the lungs and the breastbone, is crucial for efficient immune function. White blood cells are produced in bone marrow and then mature inside the thymus, where they become specialized T cells that help the body to fight infections and cancers. But the gland starts to shrink after puberty and increasingly becomes clogged with fat.

Evidence from animal and some human studies shows that growth hormone stimulates regeneration of the thymus. But this hormone can also promote diabetes, so the trial included two widely used anti-diabetic drugs, dehydroepiandrosterone (DHEA) and metformin, in the treatment cocktail.

The Thymus Regeneration, Immunorestoration and Insulin Mitigation (TRIIM) trial tested 9 white men between 51 and 65 years of age. It was led by immunologist Gregory Fahy, the chief scientific officer and co-founder of Intervene Immune in Los Angeles, and was approved by the US Food and Drug Administration in May 2015. It began a few months later at Stanford Medical Center in Palo Alto, California.

Fahy’s fascination with the thymus goes back to 1986, when he read a study in which scientists transplanted growth-hormone-secreting cells into rats, apparently rejuvenating their immune systems. He was surprised that no one seemed to have followed up on the result with a clinical trial. A decade later, at age 46, he treated himself for a month with growth hormone and DHEA, and found some regeneration of his own thymus.

In the TRIIM trial, the scientists took blood samples from participants during the treatment period. Tests showed that blood-cell count was rejuvenated in each of the participants. The researchers also used magnetic resonance imaging (MRI) to determine the composition of the thymus at the start and end of the study. They found that in seven participants, accumulated fat had been replaced with regenerated thymus tissue.

Rewinding the clock

Checking the effect of the drugs on the participants’ epigenetic clocks was an afterthought. The clinical study had finished when Fahy approached Horvath to conduct an analysis.

Horvath used four different epigenetic clocks to assess each patient’s biological age, and he found significant reversal for each trial participant in all of the tests. “This told me that the biological effect of the treatment was robust,” he says. What’s more, the effect persisted in the six participants who provided a final blood sample six months after stopping the trial, he says.

“Because we could follow the changes within each individual, and because the effect was so very strong in each of them, I am optimistic,” says Horvath.

Researchers are already testing metformin for its potential to protect against common age-related diseases, such as cancer and heart disease. Fahy says that the three drugs in the cocktail might contribute separately to the effect on biological ageing through unique mechanisms. Intervene Immune is planning a larger study that will include people of different age groups and ethnicities, and women.

Regenerating the thymus could be useful in people who have underactive immune systems, including older people, he says. Pneumonia and other infectious diseases are a major cause of death in people older than 70.

Cancer immunologist Sam Palmer at the Herriot-Watt University in Edinburgh says that it is exciting to see the expansion of immune cells in the blood. This “has huge implications not just for infectious disease but also for cancer and ageing in general”.



https://www.nature.com/articles/d41586-019-02638-w

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

Postby kurt9 » Mon Sep 09, 2019 4:45 pm

I personally know the guy behind this (I've known him for 30 years). He did this because he came up with a way to regenerate his thymus gland. This is definitely useful work and we definitely need to regenerate our thymus glands. However, we need to regenerate our lymphatic system as well in order for that regenerated thymus gland to do its job. However, the fact that biological age (as measured by the Horvoth clock) was reversed is significant in its own right.

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

Postby williatw » Wed Nov 13, 2019 6:21 am

Update about George Church's gene therapy research:


Image

How Much Can We Delay Aging? A Gene Therapy Trial Is About to Find Out
by Shelly Fan - Nov 12, 2019

Aging is reversible.

It’s still a somewhat controversial idea in humans. Yet recent attempts at delaying—or even reversing—diseases that pop up with age in animals clearly show that health doesn’t necessarily decline with age. The slip-and-slide into poor health as we age may seem like a natural trajectory, but it’s not inevitable.

In the lab, just a single treatment can often reverse aging’s nagging effects and prolong healthspan. Plenty of these are on the cusp of clinical trials: metformin and other pills, killing off senescent “zombie” cells, cutting calories, increasing exercise, or infusing “youth factors” in the blood from the young. Add to that dozens of “anti-aging” genes already proven effective in various animal models, and we have a cornucopia of ideas to fight age-related health problems—and even potentially increase lifespan.

Now here’s the mind-bender: if individual treatments already work to a degree, what happens when you combine them? How far, exactly, can we reverse the aging clock?

This week, the legendary synthetic biologist Dr. George Church and team at the Wyss Institute at Harvard University took a first step towards cracking the ultimate question of anti-aging research. They combined three gene therapies, each linked to a health problem associated with aging, into a single vaccine-like shot and gave it to ailing mice. The combination treatment reversed diabetes and obesity while improving heart and kidney function—even when those organs had already begun failing.

“If you hit enough specific diseases, you’re getting at the core aging components that are common to all of them,” said Church.

Rather than genetically modifying the mice, the team used a virus to encode genetic material that “fine-tunes” the activity of all three genes, but leaves the genome alone. In this way, the team explained, the combination therapy is far more easily applicable to humans in the long run.

“Everyone wants to stay as healthy as possible for as long as possible,” said study author Dr. Noah Davidsohn, the chief technology officer of Rejuvenate Bio, which he co-founded with Church and study author Dr. Daniel Oliver. “This study is a first step toward reducing the suffering caused by debilitating diseases.”

Last month, Rejuvenate Bio began testing a similar experimental gene therapy in aging dogs prone to heart problems. If all goes well, humans are next.

“Gene therapy gives you a testable therapy at scale in mice. And we can move from mice to dogs and then to humans. We’re focusing on the reversal of age-related diseases so we’ll be more healthy and youthful later in life,” said Church.

The Combo-Shot Dilemma

Fighting aging often feels like a game of whack-a-mole.

Age is one of the largest risk factors for a myriad of diseases—type II diabetes, liver and kidney troubles, high blood pressure, declining cognitive functions. The classic approach is to tackle each individually, but scientists have long dreamed of a single treatment to stall the development of multiple age-related diseases. For something as complex as aging, however, a single gene, protein, drug, or other “silver bullet” seems unlikely. An alternative is to stack multiple treatments into a single dose, or a combination therapy.

That’s the approach the Church team took. It’s a ballsy move. Combination gene therapies are incredibly rare, partly because they’re the equivalent to sharp-shooting multiple moving targets from a moving train and hitting the bulls-eye every single time. Miss a target—boom, nasty side effects. Hit a target too strong—wham, other unpredictable side effects. Although the idea is conceptually simple, most scientists deem it clinically impractical.

Meet the Players

The Church group went blue sky and focused on three genes well-linked to type two diabetes, heart disease, and kidney failure. Each was “packaged” into a non-toxic virus with affinity to the liver, where most of the gene products are produced.

The first is fibroblast growth factor 21 (FGF21), which keeps metabolism running smoothly and helps the body maintain its blood sugar levels. The second, alpha-Klotho, is a protein that regulates a cell’s regular activity and provides protection to heart and kidney disease. Finally, TGFbeta1 is a negative health factor that spurs age-related heart overgrowth and immune problems, and here the gene therapy is to inhibit its functions with a soluble protein called sTGFβR2.

All three genes have known roles in various age-associated diseases, the team explained. They wanted to see if changing them together could further boost health status in an additive or synergistic way, or if they actually work against each other in some way.

Immediately, FGF21 seemed to do most of the heavy lifting. Even on its own, the gene therapy reduced obesity in overweight mice, and the effects were slightly greater with the two other gene targets. With just a single shot, FGF21 also reversed type two diabetes in a diabetic mouse model, and when combined with sTGFβR2 helped kidney shrinkage in another model with kidney issues.

sTGFβR2 also worked its magic. Alone, it improved heart functions in mice with heart failure; with either of the other gene therapies, the effects were even larger.

“Collectively, these data show that a single combination therapeutic consisting of…[the two genes]…can successfully treat all four age-related disease at once,” the team concluded.

Curiously, all three gene therapies given together worsened the health outcome of some mice. Further digging found that although individually helpful, FGF21 and alpha-Klotho don’t play nice, exacerbating heart and kidney failure. Why this happens is still unclear, but it’s an important lesson for future combo-therapies: more isn’t always better in anti-aging therapies; what matters is how you stack them.

“This research marks a milestone in being able to effectively treat the many diseases associated with aging, and perhaps could lead to a means of addressing aging itself,” said Church.

From Mice to Dogs

Not everyone is on board with the “anti-aging gene therapy” claim. Because the team didn’t track overall lifespan of the treated mice, “it’s impossible to know whether they actually affected the aging process or not,” said Dr. Matt Kaeberlein at University of Washington, who was not involved in the work.

To Church and colleagues, that point’s moot. The focus isn’t on extending longevity, but rather the number of years an aged individual is in good health. Targeting age-related diseases also makes the therapies more attractive for FDA approval, since the agency doesn’t yet consider aging itself a treatable disease. What’s more important, they concede, is understanding how each component contributes to reversing various disease trajectories—who’s doing most of the work, and why combos sometimes exacerbate existing conditions.

The team is already collaborating with the American Cavalier King Charles Spaniel Club, to test the effect of FGF21 and sTGFβR2 in a small trial of 10 dogs. By age eight, these dogs often develop severe heart conditions that shorten their lifespan, and the team hopes the gene therapy can ward off the disease. If successful, they’ll gear up for larger trials that include additional breeds with other age-related health problems.

Although the study focused on only 3, Chruch has at least 45 potential anti-aging gene targets up his sleeve. Especially notable are those linked to neurodegeneration and memory loss, which the lab hopes to try in the near future.

What’s already clear is that scientists don’t have to fear combination gene therapies. “We have … demonstrated that individual longevity gene therapies can be easily combined into a single therapeutic mixture,” the team said.

There’s still a long road ahead before we can go into a drug store and get a longevity vaccine. According to Church’s estimate, the trial in dogs will likely take two years, and even if all goes well, a marketed product won’t be available for more than a decade.

But the study represents only the opening salvo of anti-aging gene therapy. We’re on the cusp of finally answering how much we can turn back the aging clock. The main thing is to get good at reversing age first, said Church. And if that truly works, there’s no upper limit to how long we’ll be able to extend healthy lives one day.






https://singularityhub.com/2019/11/12/h ... -find-out/

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

Postby williatw » Mon Nov 18, 2019 12:08 am

More on Epigenic reprogramming:


Pulsed Yamanaka Factors Set Back Epigenic Age


In a column last month, I posed the question whether the methylation clocks of Horvath are drivers of aging or responses to aging. If we intervene so as to set back the clock, are we signaling the body to be younger, or are we shutting down the repair mechanisms that the body has engaged in response to the damage of aging?

There’s a preprint from David Sinclair’s Harvard laboratory, posted on BioRxiv but not yet published, with very encouraging news for those of us who think that resetting the epigenetic (methylation) clock is a path to anti-aging. They suggest that 3 of the 4 Yamanaka factors, administered in short pulses, can set back the Horvath methylation clock without turning functioning tissues back into stem cells. The same study offers evidence to support the hypothesis that the epigenetic clock is a lethal driver of aging, rather than an adaptive response to damage.


Image

Sinclair opens the paper with an un-footnoted statement that aging consists in accumulated damage, as if this is uncontested and incontrovertible. He refers to the straight-line methylation changes that happen predictably and consistently with age as “epigenetic drift”, as if these changes were random. He believes that they are ‘loss of information” when these changes show every sign of being predictable and directed.

In the standard evolutionary paradigm, the mouse is evolved to live as long as possible, all other things being equal. (To be explicit: I don’t believe this; I think the mouse is evolved for a lifespan optimized to its ecology, not longer or shorter.) If you believe this standard paradigm, then why doesn’t the old mouse reset its epigenetic clock without our having to do it for him? In Sinclair’s account, the mouse has lost information, and can’t do it. But the Yamanaka factors are all in the mouse genome, and if that is all the information the mouse needs, we have to ask why the mouse needs us to send the signals.


We wondered whether mammalian cells might retain a faithful copy of epigenetic information from earlier in life, analogous to Shannon’s “observer” system in Information Theory, essentially a back-up copy of the original signal to allow for its reconstitution at the receiving end if information is lost or noise is introduced during transmission17.

It’s cute that Sinclair invokes Claude Shannon’s foundational theory from the 1930s on transmission errors and signal correction. But is it relevant? The reason that Sinclair and many others assume the information (how to be a young mouse) is lost is that they believe that evolution has motivated the mouse to stay young and keep making babies if only it could. If the information isn’t lost, doesn’t that defeat the very premise of Sinclair’s “lost information” theory of aging?

The point is that Sinclair is a superb experimentalist. He is also realistic enough to accept the overwhelming evidence that aging is an epigenetic program, and that the best way to influence it is to reset our epigenetics. But he is still mired in the old theory that denies it is possible for an aging program to evolve, so his efforts to frame his work in the context of “lost information” and “random drift” are strained to say the least.

Now that I’ve got that off my chest, let’s get on to the substance of this new finding, and the carefully-designed experiments that support these findings. He and co-authors demonstrate that mice treated with OSK (the first 3 out of the 4 Yamanaka factors OSKM) have restored capacity to regenerate damaged nerve cells, a capacity which is normally lost early in life. They go on to show that OSK isn’t directly responsible for regenerative capacity. And they demonstrate that resetting the methylation pattern on the mouse DNA is necessary for the restoration.

Specifically, they engineer mice with a cellular switch that can turn on OSK in response to a applied antibiotics. They flip the switch in the eyes only, then crush the optic nerve to see if it grows back. Normally, a mouse is able to regenerate nerves only while it is in early stages of development.

Yes, the nerves grow back if the eyes are pre-treated with pulsed OSK. And the benefit is lost in the absence of methyl transferase enzymes. This last result was part of the experiment in order to demonstrate that the mechanism for restoration involves re-programming methylation patterns on the chromosomes.

Image
—rDNA methylation age of 12-month-old RGCs FACS isolated from retinas infected for 4 weeks with -OSK or +OSK AAV together with short-hairpin DNAs with a scrambled sequence (sh-Scr) or targeted to Tet1 or Tet2 (sh-Tet1/sh-Tet2).

Questions not addressed yet

I’m inclined to interpret this article as much for what it doesn’t report as for what it does.

In the main experiment, OSK was induced just in the eyes, so it was just the eyes that were rejuvenated. But they also report a “safety” test done, in which OSK was induced in the whole body at a low level for an entire year without toxic effects. Of course, it’s nice to know that the low-dose OSK was not toxic and that cancer risk did not increase. But did the mice benefit from the whole-body treatment? Did they show any signs of rejuvenation, or of enhanced stem cell function?
There is a Horvath methylation clock for mice. Did the mice get younger according to the Horvath clock? The authors report that damaging the retinal nerve made the nerve cells older according to the methylation clock, and that the application of OSK brought the cells back. But I don’t see anywhere in the paper a measurement of the eye’s methylation age before and after the OSK treatment, independent of injury. For that matter, there is no discussion of the methylation age of the mice treated with whole-body OSK for a year. These omissions are curious. Are they suspicious? Have they tried and failed to set back the methylation clock, and they don’t want to report it? Certainly it’s a question I would ask if I were reviewing this ms. Maybe we’ll know the answer when the paper is published.

Did mice live longer after treatment with OSK? Answering this one takes time, and perhaps the Sinclair lab has mice even now that are living longer, but it will be a few years before we know. Or perhaps the treatment has failed so far to extend lifespan, and Sinclair is reluctant to report a failure.


https://joshmitteldorf.scienceblog.com/ ... genic-age/

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

Postby williatw » Mon Dec 09, 2019 7:54 pm

A Harvard geneticist's goal: to protect humans from viruses, genetic diseases, and aging

George Church's lab at Harvard Medical School is working to make humans immune to all viruses, eliminate genetic diseases and reverse the aging process. Scott Pelley reports on how close the geneticist's team is to a breakthrough.
Dec 08 Correspondent
Scott Pelley


Our lives have been transformed by the information age. But what's coming next is likely to be more profound, call it the genetic information age. We have mapped the human genome and in just the last few years we have learned to read and write DNA like software. And you're about to see a few breakthroughs-in-waiting that would transform human health. For a preview of this revolution in evolution we met George Church, a world leading geneticist, whose own DNA harbors many eccentricities and a few genes for genius.
George Church on using Jeffrey Epstein money

The complicated ethics of genetic engineering


We found George Church in here.

Cory Smith: Most of these are frozen George. Little bits of George that we have edited all in different tubes.

Church threw himself into his work, literally. His DNA is in many of the experiments in his lab at Harvard Medical School. The fully assembled George Church is 6'5" and 65. He helped pioneer mapping the human genome and editing DNA. Today, his lab is working to make humans immune to all viruses, eliminate genetic diseases, and reverse the effects of time.

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Scott Pelley: One of the things your lab is working on is reversing aging.

George Church: That's right.

Scott Pelley: How is that possible?

George Church: Reversing aging is one of these things that is easy to dismiss to say either we don't need it or is impossible or both.

Scott Pelley: Oh, we need it.

George Church: Okay. We need it. That's good. We can agree on that. Well, aging reversal is something that's been proven about eight different ways in animals where you can get, you know, faster reaction times or, you know, cognitive or repair of damaged tissues.

Scott Pelley: Proven eight different ways. Why isn't this available?

George Church: It is available to mice.

In lucky mice, Church's lab added multiple genes that improved heart and kidney function and levels of blood sugar. Now he's trying it in spaniels.

Scott Pelley: So is this gene editing to achieve age reversal?

George Church: This is adding genes. So, it's not really editing genes. It's, the gene function is going down, and so we're boosting it back up by putting in extra copies of the genes.

Scott Pelley: What's the time horizon on age reversal in humans?

George Church: That's in clinical trials right now in dogs. And so, that veterinary product might be a couple years away and then that takes another ten years to get through the human clinical trials.
Human trials of a personal kind made George Church an unlikely candidate to alter human evolution. Growing up in Florida, Church was dyslexic, with attention deficit, and frequently knocked out by narcolepsy.

Scott Pelley: What was it that made you imagine that you could be a scientist?

George Church: The thing that got me hooked was probably the New York World's Fair in 1964. I thought this is the way we should all be living. When I went back to Florida, I said, "I've been robbed," you know? "Where is it all?" So, I said, "Well, if they're not going to provide it, then I'm gonna provide it for myself."

With work and repetition, he beat his disabilities and developed a genius for crystallography, a daunting technique that renders 3D images of molecules through X-rays and math. But in graduate school at Duke, at the age of 20, his mania for the basic structures of life didn't leave time for the basic structure of life.

Scott Pelley: You were homeless for a time.

George Church: Yeah. Briefly.

Scott Pelley: Six months.

George Church: Six months.

Scott Pelley: And where were you sleeping when you were homeless?

George Church: Well, yeah. I wasn't sleeping that much. I was mostly working. I'm narcoleptic. So, I fall asleep sitting up anyway.

His devotion to crystallography was his undoing at Duke.

George Church: I was extremely excited about the research I was doing. And so, I would put in 100-plus hours a week on research and then pretty much didn't do anything else.

Scott Pelley: Not go to class.

George Church: I wouldn't go to class. Yeah.

Duke kicked him out with this letter wishing him well in a field other than biology. But, it turned out, Harvard needed a crystallographer. George Church has been here nearly 40 years. He employs around 100 scientists, about half-and-half men and women.

Scott Pelley: Who do you hire?

George Church: I hire people that are self-selecting, they see our beacon from a distance away. There are a lot of people that are a little, you know, might be considered a little odd. "Neuroatypicals," some of us are called.

Scott Pelley: "Neuroatypical?"

George Church: Right.

Scott Pelley: Unusual brains?

George Church: Right, yeah.


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Parastoo Khoshakhlagh: One thing about George that is very significant is that he sees what you can't even see in yourself.

Parastoo Khoshakhlagh and Alex Ng are among the "neuroatypicals." They're engineering human organ tissue.

Cory Smith: I think he tries to promote no fear of failure. The only fear is not to try at all.

Cory Smith's project sped up DNA editing from altering three genes at a time to 13,000 at a time. Eriona Hysolli went to Siberia with Church to extract DNA from the bones of wooly mammoths. She's editing the genes into elephant DNA to bring the mammoth back from extinction.

Eriona Hysolli: We are laying the foundations, perhaps, of de-extinction projects to come.

Scott Pelley: De-extinction.

Eriona Hysolli: Yes.

Scott Pelley: I'm not sure that's a word in the dictionary yet.

Eriona Hysolli: Well, if it isn't, it should be.

Scott Pelley: You know there are people watching this interview who think that is playing God.

George Church: Well, it's playing engineer. I mean, humans have been playing engineer since the dawn of time.

Scott Pelley: The point is, some people believe that you're mucking about in things that shouldn't be disturbed.

George Church: I completely agree that we need to be very cautious. And the more powerful, or the more rapidly-moving the technology, the more cautious we need to be, the bigger the conversation involving lots of different disciplines, religion, ethics, government, art, and so forth. And to see what it's unintended consequences might be.

Church anticipates consequences with a full time ethicist in the lab and he spends a good deal of time thinking about genetic equity. Believing that genetic technology must be available to all, not just those who can afford it.

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We saw one of those technologies in the hands of Alex Ng and Parastoo Khoshakhlagh. They showed us what they call "mini-brains," tiny dots with millions of cells each. They've proven that cells from a patient can be grown into any organ tissue, in a matter of days, so drugs can be tested on that patient's unique genome.

Scott Pelley: You said that you got these cells from George's skin? How does that work?

Alex Ng: We have a way to reprogram essentially, skin cells, back into a stem cell state. And we have technologies where now we can differentiate them into tissue such as brain tissue.

Scott Pelley: So you went from George's skin cells, turned those into stem cells, and turned those into brain cells.

Alex Ng: Exactly. Exactly.

Scott Pelley: Simple as that.

Organs grown from a patient's own cells would eliminate the problem of rejection. Their goal is to prove the concept by growing full sized organs from Church's DNA.

George Church: It's considered more ethical for students to do experiments on their boss than vice versa and it's good to do it on me rather than some stranger because I'm as up to speed as you can be on the on the risks and the benefits. I'm properly consented. And I'm unlikely to change my mind.

Alex Ng: We have a joke in the lab, I mean, at some point, soon probably, we're going to have more of his cells outside of his body than he has himself.

Church's DNA is also used in experiments designed to make humans immune to all viruses.

George Church: We have a strategy by which we can make any cell or any organism resistant to all viruses by changing the genetic code. So if you change that code enough you now get something that is resistant to all viruses including viruses you never characterized before.

Scott Pelley: Because the viruses don't recognize it anymore?

George Church: They expect a certain code provided by the host that they replicate in. the virus would have to change so many parts of its DNA or RNA so that it can't change them all at once. So, it's not only dead. But it can't mutate to a new place where it could survive in a new host.

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Yes, he's talking about the cure for the common cold and the end of waiting for organ transplants. It's long been known that pig organs could function in humans. Pig heart valves are routinely transplanted already. But pig viruses have kept surgeons from transplanting whole organs. Church's lab altered pig DNA and knocked out 62 pig viruses.

Scott Pelley: What organs might be transplanted from a pig to a human?

George Church: Heart, lung, kidney, liver, intestines, various parts of the eye, skin. All these things.

Scott Pelley: What's the time horizon on transplanting pig organs into human beings?

George Church: you know, two to five years to get into clinical trials. And then again it could take ten years to get through the clinical trials.

Church is a role model for the next generation. He has co-founded more than 35 startups. Recently, investors put $100 million into the pig organ work. Another Church startup is a dating app that compares DNA and screens out matches that would result in a child with an inherited disease.

George Church: You wouldn't find out who you're not compatible with. You'll just find out who you are compatible with.

Scott Pelley: You're suggesting that if everyone has their genome sequenced and the correct matches are made, that all of these diseases could be eliminated?

George Church: Right. It's 7,000 diseases. It's about 5% of the population. It's about a trillion dollars a year, worldwide.

Church sees one of his own genetic differences as an advantage. Narcolepsy lulls him several times a day. But he wakes, still in the conversation, often, discovering inspiration in his twilight zone.

Scott Pelley: If somebody had sequenced your genome some years ago, you might not have made the grade in some way.

George Church: I mean, that's true. I would hope that society sees the benefit of diversity not just ancestral diversity, but in our abilities. There's no perfect person.

Despite imperfection, Church has co-authored 527 scientific papers and holds more than 50 patents. Proof that great minds do not think alike.

The best science can tell, it was about 4 billion years ago that self-replicating molecules set off the spark of biology. Now, humans hold the tools of evolution, but George Church remains in awe of the original mystery: how chemistry became life.

Scott Pelley: Is the most amazing thing about life, then, that it happened at all?

George Church: It is amazing in our current state of ignorance. We don't even know if it ever happened ever in the rest of the universe. it's awe-inspiring to know that it either happened billions of times, or it never happened. Both of those are mind boggling. It's amazing that you can have such complex structures that make copies of themselves. But it's very hard to do that with machines that we've built. So, we're engineers. But we're rather poor engineers compared to the pseudo engineering that is biological evolution.


https://www.cbsnews.com/news/harvard-ge ... 019-12-08/


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