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#1 2021-10-27 21:03:12

RobertDyck
Moderator
From: Winnipeg, Canada
Registered: 2002-08-20
Posts: 7,936
Website

Rejuvenation - reversing aging

I've posted before about reversing aging. This is a major theme of science fiction. Some cosmetic manufacturers claim to have products that have some effect, but if they worked those products would have to go through medical approval. None have.

Many of the symptoms of aging are caused by shortening telomeres. That's the ends of chromosomes. Each time a cell divides, 6 base pairs are snipped off. When all of the telomere is gone, the enzyme that unzips a chromosome for duplication cannot latch on, so cell division stops. When this happens, a cell is called senescent. That's Latin for asleep. The cell's metabolism becomes slow, it grows large. It literally becomes fat and lazy. When this happens to too many cells, you age. Furthermore, wear can cause bits of chromosomes to break off. A telomere protects genes from damage, but once telomeres are gone, genes at the ends of chromosomes are subject to damage. Senescent cells malfunction.

Telomeres are a count-down timer. It starts at full length at conception, counts down to zero. When your cells reach zero, they can't divide, cannot produce new cells to repair tissue. There is a disease that shortens telomeres prematurely: progeria. Symptoms show us which features of aging are caused by this. Symptoms:

  • Slow height and weight growth

  • A bigger head

  • Large eyes, which they can’t close all the way

  • A small lower jaw

  • A thin nose with a "beaked" tip

  • Ears that stick out

  • Veins you can see

  • Slow and abnormal tooth growth

  • A high-pitched voice

  • Loss of body fat and muscle

  • Hair loss, including eyelashes and eyebrows

  • Thin, wrinkled skin that shows spots

The body has a means to repair telomeres. If it didn't, babies would be born with the same cellular age as the parent. Meiosis is the special type of cell division that produces a gamete cell: sperm for a man, ovum for a woman. Each gamete cell has 23 chromosomes instead of 23 pairs, a sperm must merge with an ovum for a cell to have enough chromosomes for a baby. Meiosis does a number of things, one is production of an enzyme called telomerase. This enzyme repairs telomeres to full length. So sperm and ovum have full-length telomeres.

So how do we treat this? About 2 decades ago I suggested gene therapy. Humans have the gene to produce telomerase, all we need is to activate it. The only time telomeres are shorted is during cell division, so the gene to repair telomeres only needs to be activated then. It's currently activated during meiosis, let's add an activation sequence for mitosis (normal cell division). I suggested testing this with a laboratory mouse. Shortly after I talked to everyone I could find about this, someone created the "Methuselah Mouse Prize". The purpose is to create a laboratory mouse with significantly extended life span. I guess somebody did listen.

There has been research to give us more information. In 1996 a group in Scotland cloned a sheep. The idea was to produce an expensive pharmaceutical. The drug cost thousands of dollars per gram. Their objective was to add the human gene to produce this into a sheep. To ensure the drug did not affect the sheep's growth, they ensured it would only be expressed (activated) when the genes for milk were expressed. So the drug would be produced in milk, not in the sheep's blood. The sheep would only produce a single digit number of grams per litre of milk. The drug costs thousands of dollars per gram to synthesize, but just go to any grocery store to see how much it costs to produce a litre of milk. This would make production of that drug a lot less expensive. To clone, they took a sheep body cell, remove the nucleus, did their gene modification to that nucleus. Then punched out the nucleus of a sheep ovum, put this modified nucleus in the ovum, then gave it a mild electric shock to start dividing. It worked, however the sheep had an unexpected problem: arthritis. Basically, the sheep aged prematurely. They hadn't applied sheep telomerase to lengthen telomeres before putting the cell nucleus into the ovum. So the sheep was born with its aging clock at the same point as the sheep that donated the body cell. Basically, it was conceived at the age of its parent. Oops! Ok, so the they missed a step in cloning. Ok, that's what experimentation is for. So this tells us that cloning requires applying telomerase before starting the cell to divide. Either before or after putting the cell nucleus in the ovum, but before starting cell division. This reminds us of the importance of telomeres.

We now have an opportunity. COVID vaccines uses a lipid capsule to deliver mRNA. This lipid capsule was developed specifically for gene therapy. Remember how mRNA works. When your body needs a protein, the template for that protein is a single gene on one of your chromosomes. That short section of DNA is opened, a copy is transcribed into RNA, then that section of your chromosome is closed. This strand of RNA is called messenger RNA or mRNA. That strand is taken out of the nucleus to a structure called a ribosome. The ribosome reads the RNA, every group of 3 base pairs encodes for one amino acid. Small sections of RNA called transfer RNA or tRNA carry one amino acid, and have a matching triplet of base pairs. The ribosome matches these up, links amino acids into a chain to create protein. This is how the human body makes all proteins, including telomerase. So rather than gene therapy, what we could do is inject a sequence of mRNA into human cells to produce telomerase. This would not be a permanent change, because mRNA cannot modify your genes. It's only used as a template to create protein. Can we use this to repair telomeres, reset the aging clock back to conception?

The human body has several systems. Bone growth requires growth plates. Those growth plates disappear when we reach adulthood. Any further bone growth is not possible once those growth plates are gone. So don't expect this treatment would cause you to shrink into a baby. The best it could do is reverse aging to the equivalent of 20-something. And there are probably other features of aging that this could not reverse. But it's a major step. Reset a major aging clock.

Vaccine production for Pfizer and Moderna have shown mass production of a vaccine with mRNA delivered by bilipid capsules. The only difference would be the detail strand of mRNA. The vaccines have an mRNA sequence to produce a spike protein for COVID, in the hope the human immune system will produce antibodies to latch onto this protein. Antibodies that trigger the immune system to destroy whatever the antibody is attached to. Instead of mRNA to produce a surface protein for COVID, we could produce mRNA for telomerase. Would that telomerase get into a cell's nucleus to do its job? Or would it only work for a cell that's in the process of division, when the nucleus membrane is dissolved?

Definitely something that could be tested in a lab. It could be tested with cells in a test tube or petri dish. It could be tested with tissue samples. And could be tested with laboratory mice.

This wouldn't stop aging permanently, just one treatment to reverse aging one time. It could be applied more than once, but would only reverse aging each time it's applied.

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#2 2021-10-27 21:15:02

kbd512
Administrator
Registered: 2015-01-02
Posts: 7,858

Re: Rejuvenation - reversing aging

Robert,

Has this ever been demonstrated on nerve cells?

If this works, then it would be a very neat trick.

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#3 2021-10-27 22:16:07

RobertDyck
Moderator
From: Winnipeg, Canada
Registered: 2002-08-20
Posts: 7,936
Website

Re: Rejuvenation - reversing aging

kbd512,
I just came up with the idea. It hasn't been demonstrated by anyone.

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#4 2021-10-28 06:22:38

tahanson43206
Moderator
Registered: 2018-04-27
Posts: 19,436

Re: Rejuvenation - reversing aging

For RobertDyck re new topic...

Bravo!

SearchTerm:Invention by RobertDyck as posted in NewMars forum, 2021
SearchTerm:telemeres restoration of

Your announcement occurs on the very same Earth day that a medical student interested in Mars arrives in the forum.

I note in particular that our new member has chosen the somewhat morbid Signature of momento mori.

Having spent a couple of weeks interacting with Clinician_Antilles, I suspect your idea will be of interest.

An entire career could be devoted to investigating the practicality of your idea, and potentially implementing it for the entire human population if it is viable.

If we dramatically extend life on Earth, we will provide incentive to expand to Mars and other Solar System destinations, because the Earth is already showing signs of excess population.

(th)

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#5 2021-10-28 09:17:10

RobertDyck
Moderator
From: Winnipeg, Canada
Registered: 2002-08-20
Posts: 7,936
Website

Re: Rejuvenation - reversing aging

Actually, population growth has dramatically slowed. In all developed countries, population is shrinking. Developed countries have to accept large numbers of immigrants to maintain population. Scientists who study population are called geographers. Yea, that's study of population and demographics, not land forms. You may think that a couple must have two babies to replace themselves, but due to children who die before reaching adulthood and a few other technical issues, just maintaining population requires 2.1 babies per woman on average. Scientists call this "fertility rate". Medical science defines that term completely differently, but lets use the term the way geographers define it. Fertility rate this year for the United States is 1.781, for Russia 1.823, China 1.699, Brazil 1.697. India has 2.1; it's difficult to measure in rural areas, some estimates make the 3rd significant figure slighter higher, other estimates slightly lower. It's only accurate to 2 significant figures, and it's 2.1, which is neither growth nor shrinking. Fertility rate in Canada is 1.47. Developed countries have maintained population growth by accepting large numbers of immigrants from 3rd world countries. World population today is 7.9 billion, scientists estimate population will peak in year 2060 at 8.0 billion, then shrink. So world population will only grow 0.1 billion in the next 39 or 40 years.

The United Nations is still using population models from the early 1970s that predicted population growth forever. Bureaucracy in the UN apparently is an order of magnitude worse than national governments. Even though scientists have published books about this, published multiple peer reviewed science papers. Every developed country has a department maintaining population statistics, measuring the above figures. Yet, the bureaucrats in the UN refuse to update their mathematical models. Their models are half a century old.

So now definitely is the time to develop life extension technology.

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#6 2021-10-28 09:31:10

RobertDyck
Moderator
From: Winnipeg, Canada
Registered: 2002-08-20
Posts: 7,936
Website

Re: Rejuvenation - reversing aging

As usual, click image for web page this comes from.
Fertility-rate-Canada-1.png

As a personal anecdote, my mother was born in 1938. She was one of 4; she had two brothers and one sister. My father was born in 1932. He was one of 11. One child died at 3 months, if you count that one he was one of 12. He had 8 brothers and 2 sisters, all of whom got married and had children. My brother and his wife had one daughter. My sister married an older man who had 2 children by a previous marriage. They had one daughter. She since got divorced, and remarried. Her current husband was not previously married, and they didn't have any children. I haven't had any children. So that's a total of 7 adults, and 4 children. I would like to get married and have a baby, but at my age that isn't likely to happen.

One ancestor on my mother's side was even more dramatic. In the 1800s, my great great grandfather? Or one generation before that? A widower had 8 children, he married a widow who also had 8 children. They had one more baby. So that's 17 children! I hope the oldest were adult before the youngest baby was born.

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#7 2021-10-28 10:14:31

tahanson43206
Moderator
Registered: 2018-04-27
Posts: 19,436

Re: Rejuvenation - reversing aging

For RobertDyck ... since you have already confirmed you are able (and willing) to connect to the NewMarsMember Zoom site, I'd like to be sure you are aware that our new member has indicated an interest in a Zoom meeting with selected forum members.  I am currently working on such a meeting.

If you are interested in such a meeting, please let us (forum) know.  I'd be glad to facilitate such a meeting if both you and our new member are interested.

He is ** just ** at the cusp of deciding where to pursue his medical studies.  Your (I'll call it "invention") of telemere extension using technology developed to fight Covid is mighty interesting to me (for sure) and it it may be interesting to someone just starting on a career in medicine.

(th)

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#8 2021-10-28 10:56:13

RobertDyck
Moderator
From: Winnipeg, Canada
Registered: 2002-08-20
Posts: 7,936
Website

Re: Rejuvenation - reversing aging

Call it an idea? Thomas Edison said invention is 1% inspiration, 99% perspiration. I haven't done any work. I have some knowledge, but not the formal education in medicine. I've studied aerospace engineering far more. And my formal university education is computer science. I'm really only qualified to be a software developer. The pieces for this "invention" have been developed by others; at this point it's just a matter of putting existing pieces together.

By the way, the mRNA vaccines (Pfizer and Moderna) were developed from technology that was originally intended for gene therapy. So in a way this is applying COVID technology, but more accurately it's gene therapy technology. Using it for life extension / rejuvenation is closer to what it was originally intended for.

Ps. If you want a conspiracy theory, both Pfizer and Moderna started working on these vaccines in 2015. They were generically working on a vaccine for respiratory RNA corona viruses. When COVID came out, they said just give us a sample of the virus and we'll give you a vaccine in 48 hours. So why were they working on something so specific in 2015? Government intelligence (CIA, CSIS in Canada, MI6 in the UK, etc) had a document in 2015 from the People's Liberation Army of China detailing how to use SARS to collapse the healthcare system of a target country. It's my belief that the government asked pharmaceutical companies to develop a vaccine in case China released it. COVID came from the city of Wuhan, location of the Wuhan Institutue of Virology. Looks like COVID is something they were working on that got out by a careless worker. Not exactly a huge conspiracy; if this hypothesis is correct, that means government was just preparing to protect us. Why don't they just admit to it? Of course that also means the vaccine is a military vaccine. The anthrax vaccine didn't work that well, did it?

Anyway. Yes, I'm available. Just tell me when so I can put a shirt on.

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#9 2021-10-28 11:14:15

tahanson43206
Moderator
Registered: 2018-04-27
Posts: 19,436

Re: Rejuvenation - reversing aging

For RobertDyck .... re #8 and topic ....

Your modesty is noted << !!! >>

Thanks for your offer!  I'll pass along to C_A asap.

(th)

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#10 2021-10-28 17:33:36

SpaceNut
Administrator
From: New Hampshire
Registered: 2004-07-22
Posts: 29,433

Re: Rejuvenation - reversing aging

Many of man's discoveries have happened in that same manner via accident.

Growth hormones are an accelerator so why not a reverse or slow down drug....

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#11 2021-10-28 18:11:05

RobertDyck
Moderator
From: Winnipeg, Canada
Registered: 2002-08-20
Posts: 7,936
Website

Re: Rejuvenation - reversing aging

Slowing down *IS* the problem. You need your cells to multiply to replace damaged tissue.

And bones require a certain metabolic speed. Osteoclasts are cells that dissolve bone, releasing calcium into your blood. Your body need calcium, one function of bones is calcium storage. Osteoblasts are cells that build bone. When bones are stressed, that stimulates nerves which trigger a cascade of reactions which signal ostoblasts to thicken bone where it was stimulated. The balance between dissolving bone and building new bone optimizes bone to be what you need for your current level of activity. Of course this means you can't suddenly increase stress on your bones, because they won't be optimized for that. When metabolism slows too much, the processes of cannot respond quickly enough to maintain optimum strength. Bones become soft as osteoclasts dissolve bone to release calcium, but osteoblasts cannot rebuild them fast enough to maintain strength. The result is called osteoporosis.

Fix for osteoporosis is two fold: ensure there's no nerve damage in the bones. If nerves cannot detect stress, they cannot trigger osteoblasts to strengthen bone when they become too thin. The other is to speed metabolism. Human metabolism of the very old becomes so slow that weakness is a serious danger. Some elderly have engaged in a regular exercise regimen to ensure muscle and bone retain strength. But that must be continuous, because elderly bodies cannot respond quickly enough. Young people can engage in sporadic or rare exercise and it's enough, elderly must do it constantly.

Part of rejuvenation is to speed metabolism so it responds like a younger person. Many elderly in their 80s would love to have a body equivalent to 60.

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#12 2021-10-28 21:11:54

RobertDyck
Moderator
From: Winnipeg, Canada
Registered: 2002-08-20
Posts: 7,936
Website

Re: Rejuvenation - reversing aging

Fixed the wall-mount for my monitor with the camera. Gives me a lot more desk space. Moved the camera back. Point is monitor and camera are ready for Zoom now.

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#13 2021-10-29 15:50:35

Terraformer
Member
From: The Fortunate Isles
Registered: 2007-08-27
Posts: 3,907
Website

Re: Rejuvenation - reversing aging

I don't know why people always worry about overpopulation when it comes to longevity. It's only a potential problem if the menopause is also done away with. Otherwise women will still only have a small fertile window (relative to their centuries long lifespans) in which to have children, so we won't get couples making a new family every century. There'll still be growth, but it will be linear, not exponential. We added an estimate 140 million people in 2020, so if no-one died anymore and we continued at the same rate we'd have 50 years before the population doubled, 100 before it tripled. Estimates vary for the planets carrying capacity, but I think we could handle that.


Use what is abundant and build to last

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#14 2021-10-31 12:20:41

RobertDyck
Moderator
From: Winnipeg, Canada
Registered: 2002-08-20
Posts: 7,936
Website

Re: Rejuvenation - reversing aging

I haven't heard anything from our new member. Has my modesty scared him off? Is he not interested? Would like to know what's happening.

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#15 2021-10-31 14:17:46

tahanson43206
Moderator
Registered: 2018-04-27
Posts: 19,436

Re: Rejuvenation - reversing aging

For Terraformer re #13 .... artificial wombs are very close .... science fiction writers have been anticipating them for decades.  The stock of eggs is what appears to be limited, and every one currently discarded could be preserved if there were a need.

For RobertDyck ... A_C is likely to be participating on a weekly basis.  He is right in the middle of trying to find a medical school.  He's interested in aerospace medicine, and we discussed a couple of possibilities.  Everything else is secondary to that activity.

Please consider writing to Moderna ... I understand (from TV interviews with their founder) that Moderna played a major role in developing this new technology.  They might be quite interested in your idea, although the need to ramp up production to serve the entire world no doubt takes priority right now.

(th)

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#16 2021-11-07 18:53:41

Clinician_Antilles
InActive
From: X-Wing
Registered: 2020-10-29
Posts: 13

Re: Rejuvenation - reversing aging

Hi RobertDyck,

My apologies for the delay, like tahanson43206 mentioned I am in the middle of applying to medical schools while working full time, so I have been having a few problems with being as active as I would like to be.

If it's alright with you, please give me today and tomorrow to read over this and gather my thoughts/current research. If you would like, perhaps after doing this I can recount my thoughts to you over a call to facilitate our discussion a bit faster than the forum?

Let me know what you think!


memento mori

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#17 2021-11-07 19:13:51

louis
Member
From: UK
Registered: 2008-03-24
Posts: 7,208

Re: Rejuvenation - reversing aging

You need to get philosophical before you start thinking extending ageing is going to be a wonderful benefit.

There will be horrific consequences.

Firstly the planet's resources will be put under extreme stress. If no one dies over the next 200 years I guess we could be heading for a population maybe 50  times what it is now. So 300 billion. Is that a sensible population for a planet our size? I don't think so. Okay perhaps we can start  developing other planets but I doubt Mars will be able to support half that population ie 150 billion in the next 200 years and there aren't many other potential homes in the solar system.

I am not saying Earth couldn't support 300 billion people but I am saying it would be a horrible place to live.

In any case there's no way you could support the huge number of immortals through the existing economy, in which only a small proportion of the population will be invovled. You would have to raise the retirement age, so the reality would be that whereas people only used to have to work 30 or so years, now they will have to work maybe 100 years.

Our social and biological structures are not designed to cope with extreme age or immortality. We currently (if we are lucky) feel close to and feel affection for our living family memebrs. How will we feel about 2000 living "close" family members. Most obviously they won't be "close". We will have to pick and choose...but how will that play out in terms of inheritance and wills?

The rythm of our culture which is based on the idea of brief youth, parenthood, grandparenthood and death will be completely destroyed.
You will have to reinvent culture but it's difficult to just summon up culture in a few years. Most culture develop over centuries through accretion.  My point is that humans will be set adrift with no cultural anchors.


Let's Go to Mars...Google on: Fast Track to Mars blogspot.com

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#18 2021-11-07 19:26:15

louis
Member
From: UK
Registered: 2008-03-24
Posts: 7,208

Re: Rejuvenation - reversing aging

Yes I've posted pics before now of goats I think it were who can survive and develop  in artificial sacs for months. Bascially it's like a tunnel - one team boring from one end and another from the other end...eventually they are going to meet in the middle. I think they can keep foetuses  alive in the sacs for something like 14 weeks and at the other end they can keep a foetus alive from about 24 weeks. So you have a 10 week gap.  Of course it's more complicated than that (very early birth babies are often disabled for life)  but probably within the next 30 years we will have the technology to protect the foetus all the way through to "birth". 

That could have huge implications for Mars colonisation because of course it raises the prospect that you could create a Mars population from scratch through sperm donation and fertilised egg farming. That raises a huge range of ethical issues.

One response might be to envisage a Mars culture that is more like the Victorian family culture where it was quite normal to have 10 children in one family unit. The difference would be that women wouldn't have to go through multiple labours.



tahanson43206 wrote:

For Terraformer re #13 .... artificial wombs are very close .... science fiction writers have been anticipating them for decades.  The stock of eggs is what appears to be limited, and every one currently discarded could be preserved if there were a need.

For RobertDyck ... A_C is likely to be participating on a weekly basis.  He is right in the middle of trying to find a medical school.  He's interested in aerospace medicine, and we discussed a couple of possibilities.  Everything else is secondary to that activity.

Please consider writing to Moderna ... I understand (from TV interviews with their founder) that Moderna played a major role in developing this new technology.  They might be quite interested in your idea, although the need to ramp up production to serve the entire world no doubt takes priority right now.

(th)


Let's Go to Mars...Google on: Fast Track to Mars blogspot.com

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#19 2021-11-15 19:21:32

Clinician_Antilles
InActive
From: X-Wing
Registered: 2020-10-29
Posts: 13

Re: Rejuvenation - reversing aging

RobertDyck wrote:

I've posted before about reversing aging. This is a major theme of science fiction. Some cosmetic manufacturers claim to have products that have some effect, but if they worked those products would have to go through medical approval. None have.

Many of the symptoms of aging are caused by shortening telomeres. That's the ends of chromosomes. Each time a cell divides, 6 base pairs are snipped off. When all of the telomere is gone, the enzyme that unzips a chromosome for duplication cannot latch on, so cell division stops. When this happens, a cell is called senescent. That's Latin for asleep. The cell's metabolism becomes slow, it grows large. It literally becomes fat and lazy. When this happens to too many cells, you age. Furthermore, wear can cause bits of chromosomes to break off. A telomere protects genes from damage, but once telomeres are gone, genes at the ends of chromosomes are subject to damage. Senescent cells malfunction.

Telomeres are a count-down timer. It starts at full length at conception, counts down to zero. When your cells reach zero, they can't divide, cannot produce new cells to repair tissue. There is a disease that shortens telomeres prematurely: progeria. Symptoms show us which features of aging are caused by this. Symptoms:

  • Slow height and weight growth

  • A bigger head

  • Large eyes, which they can’t close all the way

  • A small lower jaw

  • A thin nose with a "beaked" tip

  • Ears that stick out

  • Veins you can see

  • Slow and abnormal tooth growth

  • A high-pitched voice

  • Loss of body fat and muscle

  • Hair loss, including eyelashes and eyebrows

  • Thin, wrinkled skin that shows spots

The body has a means to repair telomeres. If it didn't, babies would be born with the same cellular age as the parent. Meiosis is the special type of cell division that produces a gamete cell: sperm for a man, ovum for a woman. Each gamete cell has 23 chromosomes instead of 23 pairs, a sperm must merge with an ovum for a cell to have enough chromosomes for a baby. Meiosis does a number of things, one is production of an enzyme called telomerase. This enzyme repairs telomeres to full length. So sperm and ovum have full-length telomeres.

So how do we treat this? About 2 decades ago I suggested gene therapy. Humans have the gene to produce telomerase, all we need is to activate it. The only time telomeres are shorted is during cell division, so the gene to repair telomeres only needs to be activated then. It's currently activated during meiosis, let's add an activation sequence for mitosis (normal cell division). I suggested testing this with a laboratory mouse. Shortly after I talked to everyone I could find about this, someone created the "Methuselah Mouse Prize". The purpose is to create a laboratory mouse with significantly extended life span. I guess somebody did listen.

There has been research to give us more information. In 1996 a group in Scotland cloned a sheep. The idea was to produce an expensive pharmaceutical. The drug cost thousands of dollars per gram. Their objective was to add the human gene to produce this into a sheep. To ensure the drug did not affect the sheep's growth, they ensured it would only be expressed (activated) when the genes for milk were expressed. So the drug would be produced in milk, not in the sheep's blood. The sheep would only produce a single digit number of grams per litre of milk. The drug costs thousands of dollars per gram to synthesize, but just go to any grocery store to see how much it costs to produce a litre of milk. This would make production of that drug a lot less expensive. To clone, they took a sheep body cell, remove the nucleus, did their gene modification to that nucleus. Then punched out the nucleus of a sheep ovum, put this modified nucleus in the ovum, then gave it a mild electric shock to start dividing. It worked, however the sheep had an unexpected problem: arthritis. Basically, the sheep aged prematurely. They hadn't applied sheep telomerase to lengthen telomeres before putting the cell nucleus into the ovum. So the sheep was born with its aging clock at the same point as the sheep that donated the body cell. Basically, it was conceived at the age of its parent. Oops! Ok, so the they missed a step in cloning. Ok, that's what experimentation is for. So this tells us that cloning requires applying telomerase before starting the cell to divide. Either before or after putting the cell nucleus in the ovum, but before starting cell division. This reminds us of the importance of telomeres.

We now have an opportunity. COVID vaccines uses a lipid capsule to deliver mRNA. This lipid capsule was developed specifically for gene therapy. Remember how mRNA works. When your body needs a protein, the template for that protein is a single gene on one of your chromosomes. That short section of DNA is opened, a copy is transcribed into RNA, then that section of your chromosome is closed. This strand of RNA is called messenger RNA or mRNA. That strand is taken out of the nucleus to a structure called a ribosome. The ribosome reads the RNA, every group of 3 base pairs encodes for one amino acid. Small sections of RNA called transfer RNA or tRNA carry one amino acid, and have a matching triplet of base pairs. The ribosome matches these up, links amino acids into a chain to create protein. This is how the human body makes all proteins, including telomerase. So rather than gene therapy, what we could do is inject a sequence of mRNA into human cells to produce telomerase. This would not be a permanent change, because mRNA cannot modify your genes. It's only used as a template to create protein. Can we use this to repair telomeres, reset the aging clock back to conception?

The human body has several systems. Bone growth requires growth plates. Those growth plates disappear when we reach adulthood. Any further bone growth is not possible once those growth plates are gone. So don't expect this treatment would cause you to shrink into a baby. The best it could do is reverse aging to the equivalent of 20-something. And there are probably other features of aging that this could not reverse. But it's a major step. Reset a major aging clock.

Vaccine production for Pfizer and Moderna have shown mass production of a vaccine with mRNA delivered by bilipid capsules. The only difference would be the detail strand of mRNA. The vaccines have an mRNA sequence to produce a spike protein for COVID, in the hope the human immune system will produce antibodies to latch onto this protein. Antibodies that trigger the immune system to destroy whatever the antibody is attached to. Instead of mRNA to produce a surface protein for COVID, we could produce mRNA for telomerase. Would that telomerase get into a cell's nucleus to do its job? Or would it only work for a cell that's in the process of division, when the nucleus membrane is dissolved?

Definitely something that could be tested in a lab. It could be tested with cells in a test tube or petri dish. It could be tested with tissue samples. And could be tested with laboratory mice.

This wouldn't stop aging permanently, just one treatment to reverse aging one time. It could be applied more than once, but would only reverse aging each time it's applied.

Hi Mr. Dyck,

Thank you for such an interesting idea and detailed post! In response to your question, I think that this delivery method would be difficult considering that surface proteins and telomerase are going as you mentioned to two separate locations. The COVID 19 mechanism utilized mRNA to directly access ribosomes that are sending their products out rather than in (extracellular spike protein). My understanding as to how this is accomplished (although mostly only from my college education) is in order to to send a protein to the nucleus, it would have to be tagged with a nuclear localization sequence which could be attached to a telomerase end product. You raise another good point by asking about the nuclear membrane, from my understanding proteins are transported through the membrane, such as histones. I found this paper detailing the whole process more, while I have not been able to absorb it entirely due to time constraints in my life currently you may find some use in it:

https://sci-hub.se/10.1016/0092-8674(91)90233-O

Perhaps the same method could be used, but of course this is dependent on protein size, energy cost, etc etc.

The secondary problem which you mentioned was that would this work for somatic vs germline cells. I believe in order to induce the events of this in somatic cells, it requires that we first observe the germline cells to see what mechanism they are acting by. After having an idea of how this works, perhaps it would be possible to induce a somatic cell to do the same. With advances in stem cell biology such IPS cells, the realm of what is possible/what we can induce in a controlled environment is rapidly changing.

I wanted to ask further about the Methuselah Mouse Prize, what were the findings they had? I wonder if they learned anything about this mechanism from their competition.


memento mori

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#20 2021-11-16 14:33:11

RobertDyck
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From: Winnipeg, Canada
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Re: Rejuvenation - reversing aging

Thank you for responding.

I remind you, the lipid capsule was originally developed to deliver gene therapy. One problem the mRNA vaccines are experiencing is the lipid capsule delivers to all cells throughout the body, not just lymph nodes. So rather than delivering the antigen directly to the lymph nodes were new antibodies are developed, they're delivered throughout the body where the spike proteins can cause damage. And it turns out the spike proteins are not inert, they are causing damage. But I don't want to get into a debate about effectiveness of particular vaccines, the point is the vector was developed to deliver gene therapy.

Thank you for the document. I am reading it. Meanwhile I here is an article from Wikipedia: Telomerase

Telomerase restores short bits of DNA known as telomeres, which are otherwise shortened when a cell divides via mitosis.

In normal circumstances, where telomerase is absent, if a cell divides recursively, at some point the progeny reach their Hayflick limit, which is believed to be between 50 and 70 cell divisions. At the limit the cells become senescent and cell division stops. Telomerase allows each offspring to replace the lost bit of DNA, allowing the cell line to divide without ever reaching the limit. This same unbounded growth is a feature of cancerous growth.

Embryonic stem cells express telomerase, which allows them to divide repeatedly and form the individual. In adults, telomerase is highly expressed only in cells that need to divide regularly, especially in male sperm cells, but also in epidermal cells, in activated T cell and B cell lymphocytes, as well as in certain adult stem cells, but in the great majority of cases somatic cells do not express telomerase.

A comparative biology study of mammalian telomeres indicated that telomere length of some mammalian species correlates inversely, rather than directly, with lifespan, and concluded that the contribution of telomere length to lifespan is unresolved. Telomere shortening does not occur with age in some postmitotic tissues, such as in the rat brain. In humans, skeletal muscle telomere lengths remain stable from ages 23 –74. In baboon skeletal muscle, which consists of fully differentiated post-mitotic cells, less than 3% of myonuclei contain damaged telomeres and this percentage does not increase with age. Thus, telomere shortening does not appear to be a major factor in the aging of the differentiated cells of brain or skeletal muscle. In human liver, cholangiocytes and hepatocytes show no age-related telomere shortening. Another study found little evidence that, in humans, telomere length is a significant biomarker of normal aging with respect to important cognitive and physical abilities.

Some experiments have raised questions on whether telomerase can be used as an anti-aging therapy, namely, the fact that mice with elevated levels of telomerase have higher cancer incidence and hence do not live longer. On the other hand, one study showed that activating telomerase in cancer-resistant mice by overexpressing its catalytic subunit extended lifespan.

A study that focused on Ashkenazi Jews found that long-lived subjects inherited a hyperactive version of telomerase.

This makes it more complicated. The "scare" of cancer is something I have heard many times. Individuals claimed that the fact cancers cells produce telomerase means telomerase will cause cancer. That doesn't follow: all cruise missiles use jet fuel, but not everything that uses jet fuel is a cruise missile. In fact there was a study to see if a telomerase inhibitor would restrict cancer growth. The hypothesis was after a certain number of cell divisions, the cancer could not grow any further. However, experiments showed absolutely no effect. The described study with mice shows no conclusive effect. Again, fear. Rather than doing nothing based on fear, instead do the research. As the article stated, telomerase has shown to extend the lifespan of cancer resistant mice. So telomerase does not cause cancer.

It's interesting that some body cells produce telomerase.

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#21 2021-11-16 15:01:50

RobertDyck
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From: Winnipeg, Canada
Registered: 2002-08-20
Posts: 7,936
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Re: Rejuvenation - reversing aging

I should point out skin, connective tissue, body fat, and hair appear to suffer from shortened telomeres. And endocrine glands. Loss of hormones is another cause of aging. If telomerase treatment can rejuvenate endocrine glands, that will fix another whole batch of symptoms.

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#22 2021-11-17 21:54:27

tahanson43206
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Registered: 2018-04-27
Posts: 19,436

Re: Rejuvenation - reversing aging

For RobertDyck ... the upcoming Axiom flight includes a study for Mao Clinic of senescent cells

https://www.yahoo.com/news/1st-axiom-la … 00325.html

For 1st Axiom launch with SpaceX, civilian science plays into new space station goals
Richard Tribou, Orlando Sentinel
Wed, November 17, 2021 9:00 AM

“That’s what I’m excited about,” he said. “It’s not about being the pilot. It’s about doing things that can only be done in space – experiments in microgravity. It’s a unique way to help humankind.”

The main experiment is on senescent cells, which are cells that have stopped dividing and are linked to many age-related diseases. He’s also performing an experiment on heart health. Before and after launch, Connor will also submit to MRIs so researchers can see the effect of spaceflight on spinal and brain tissue.

(th)

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#23 2021-11-18 01:17:58

Clinician_Antilles
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From: X-Wing
Registered: 2020-10-29
Posts: 13

Re: Rejuvenation - reversing aging

Hi Mr. Dyck,

Another interesting point about that is that Kernal Biologics recently presented at the ISSRDC convention this year about how their genetically engineered mRNA has been shown to selectively target cancer cells. It's still in clinical trials, but I'm sure the presence of treatments like that will help to dispel the fear around telomere experimentation. This will undoubtedly be a hot topic in research going forward, I wonder if in our dialogue we can try to isolate a scientific process to test this? I'd love to work with you on this if you are interested.

Some body cells have to, as they are responsible for regenerating the rest of our bodies cells. Maybe the question we should ask is when do THESE cells stop? Assuming they do and there is a general timeline, that would be the optimum time to do such a treatment.

Mr. Hanson helps add to my point...people with far more resources than us are debating this. I do have some friends who are studying for their masters in microbiology...if you like I can bounce your idea around to them and see what they think?


memento mori

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#24 2021-11-18 07:38:29

tahanson43206
Moderator
Registered: 2018-04-27
Posts: 19,436

Re: Rejuvenation - reversing aging

For C_A re #23

You are sure to receive encouragement to discuss the mRNA/telomeres idea with as many of your friends and acquaintances as you can possibly reach. You ** could ** for example, post a notice about the topic in a print (or online) publication, as a way of gathering talented individuals to work on this.  This is a case where the ** more ** cooks you have in the kitchen, most definitely the better!

There is a Nobel prize in the future for someone who can achieve realization of RobertDyck's idea.  We are the only ones who will ever know he was the source of inspiration, but ** we ** WILL know, and be able to celebrate achievement by others when they occur.

(th)

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#25 2021-12-04 19:33:49

SpaceNut
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From: New Hampshire
Registered: 2004-07-22
Posts: 29,433

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