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Dr Aubrey de Grey - Rejuvenating biotech: Why age may soon cease to mean aging


Matt

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"Dr. Aubrey De Grey is a biomedical gerontologist and the Chief Science Officer at SENS Research Foundation, a biomedical charity that funds research dedicated to combating aging. His research interests encompass the characterization of all the accumulating and eventually pathogenic molecular and cellular side-effects of metabolism (“damage”) that constitute mammalian aging, and the design of interventions to repair and/or obviate that damage. In line with his research, De Grey gave a talk at The Aspen Abu Dhabi Ideas Festival focusing on “Rejuvenating Biotechnology: Why age may soon cease to mean aging”."

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And here is someone who did an NIH supported study that insists it is mathematically(!?) impossible to stop aging for any multicellular organism:
 

It's mathematically impossible to beat aging, scientists say

 

""Aging is mathematically inevitable -- like, seriously inevitable. There's logically, theoretically, mathematically no way out," said Joanna Masel, professor of ecology and evolutionary biology and at the UA."

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And here is someone who did an NIH supported study that insists it is mathematically(!?) impossible to stop aging for any multicellular organism:

 

It's mathematically impossible to beat aging, scientists say

 

""Aging is mathematically inevitable -- like, seriously inevitable. There's logically, theoretically, mathematically no way out," said Joanna Masel, professor of ecology and evolutionary biology and at the UA."

 

This is true, but at the same time, a weak argument.  Of course you can't stop living systems from deteriorating, but in theory you can replace worn out cells, of course we don't have this any where near perfected yet, so its easy to say its just impractical wishful thinking, but you get the same sort of naysayers around virtually all technology, its been happening for thousands of years.  As long as the sun is still shining, we have essentially unlimited input energy (no closed systems on the planet) which means we have essentially unlimited potential for rejuvenation without breaking any laws of thermodynamics ;)xyz.

 

Scientists prove ‘immortal worms’ can regenerate indefinitely and stay forever young

 

See the section on "modern developments" under:

https://en.wikipedia.org/wiki/Rejuvenation_(aging)

 

Aging is an accumulation of damage to macromoleculescellstissues and organs. If any of that damage can be repaired, the result is rejuvenation.

There have been many experiments which have been shown to increase the maximum life span of laboratory animals[citation needed], thereby achieving life extension. A few experimental methods such as replacing hormones to youthful levels have had considerable success in partially rejuvenating laboratory animals and humans. A recent experiment involved breeding genetically manipulated mice that lacked an enzyme called telomerase, causing the mice to age prematurely and suffer ailments. When the mice were given injections to reactivate the enzyme, it repaired the damaged tissues and reversed the signs of aging.[9] There are at least eight important hormones that decline with age: 1. human growth hormone(HGH); 2. the sexual hormones: testosterone or oestrogen/progesterone; 3. erythropoietin (EPO); 4. insulin; 5. DHEA; 6. melatonin; 7. thyroid; 8. pregnenolone. In theory, if all or some of these hormones are replaced, the body will respond to them as it did when it was younger, thus repairing and restoring many body functions. In line with this, recent experiments show that heterochronic parabiosis, i.e. connecting the circulatory systems of young and old animal, leads to the rejuvenation of the old animal, including restoration of proper stem cell function. Similar experiments show that grafting old muscles into young hosts leads to their complete restoration, whereas grafting young muscles into old hosts does not. These experiments show that aging is mediated by systemic environment, rather than being an intrinsic cell property[citation needed]. Clinical trials based on transfusion of young blood were scheduled to begin in 2014.[10]

Most attempts at genetic repair have traditionally involved the use of a retrovirus to insert a new gene into a random position on a chromosome. But by attaching zinc fingers (which determine where transcription factors bind) to endonucleases(which break DNA strands), homologous recombination can be induced to correct and replace defective (or undesired) DNA sequences. The first applications of this technology are to isolate stem cells from the bone marrow of patients having blood disease mutations, to correct those mutations in laboratory dishes using zinc finger endonucleases and to transplant the stem cells back into the patients.[11]

Stem cell regenerative medicine uses three different strategies:

  1. Implantation of stem cells from culture into an existing tissue structure
  2. Implantation of stem cells into a tissue scaffold that guides restoration
  3. Induction of residual cells of a tissue structure to regenerate the necessary body part

salamander can not only regenerate a limb, but can regenerate the lens or retina of an eye and can regenerate an intestine. For regeneration the salamander tissues form a blastema by de-differentiation of mesenchymal cells, and the blastema functions as a self-organizing system to regenerate the limb.[12]

Yet another option involves cosmetic changes to the individual to create the appearance of youth. These are generally superficial and do little to make the person healthier or live longer, but the real improvement in a person's appearance may elevate their mood and have positive side effects normally correlated with happinessCosmetic surgery is a large industry offering treatments such as removal of wrinkles ("face lift"), removal of extra fat (liposuction) and reshaping or augmentation of various body parts (abdomenbreastsface).

There are also, as commonly found throughout history, many fake rejuvenation products that have been shown to be ineffective. Chief among these are powders, sprays, gels, and homeopathic substances that claim to contain growth hormones. Authentic growth hormones are only effective when injected, mainly due to the fact that the 191-amino acid protein is too large to be absorbed through the mucous membranes, and would be broken up in the stomach if swallowed.

The Mprize scientific competition is under way to deliver on the mission of extending healthy human life. It directly accelerates the development of revolutionary new life extension therapies by awarding two cash prizes: one to the research team that breaks the world record for the oldest-ever mouse; and one to the team that develops the most successful late-onset rejuvenation. Current Mprize winner for rejuvenation is Steven Spindler. Caloric restriction (CR), the consumption of fewer calories while avoiding malnutrition, was applied as a robust method of decelerating aging and the development of age-related diseases.[13]

Strategies for Engineered Negligible Senescence[edit]

The biomedical gerontologist Aubrey de Grey has initiated a project, Strategies for Engineered Negligible Senescence (SENS), to study how to reverse the damage caused by aging. He has proposed seven strategies for what he calls the seven deadly sins of aging:[14]

  1. Cell loss can be repaired (reversed) just by suitable exercise in the case of muscle. For other tissues it needs various growth factors to stimulate cell division, or in some cases it needs stem cells.
  2. Senescent cells can be removed by activating the immune system against them. Or they can be destroyed by gene therapy to introduce "suicide genes" that only kill senescent cells.
  3. Protein cross-linking can largely be reversed by drugs that break the links. But to break some of the cross-links we may need to develop enzymatic methods.
  4. Extracellular garbage (like amyloid) can be eliminated by vaccination that gets immune cells to "eat" the garbage.
  5. For intracellular junk we need to introduce new enzymes, possibly enzymes from soil bacteria, that can degrade the junk (lipofuscin) that our own natural enzymes cannot degrade.
  6. For mitochondrial mutations the plan is not to repair them but to prevent harm from the mutations by putting suitably modified copies of the mitochondrial genes into the cell nucleus by gene therapy. The mitochondrial DNA experiences a high degree of mutagenic damage because most free radicals are generated in the mitochondria. A copy of the mitochondrial DNA located in the nucleus will be better protected from free radicals, and there will be better DNA repairwhen damage occurs. All mitochondrial proteins would then be imported into the mitochondria.
  7. For cancer (the most lethal consequence of mutations) the strategy is to use gene therapy to delete the genes for telomerase and to eliminate telomerase-independent mechanisms of turning normal cells into "immortal" cancer cells. To compensate for the loss of telomerase in stem cells we would introduce new stem cells every decade or so.[15]

In 2009, Aubrey de Grey co-founded the SENS Foundation to expedite progress in the above-listed areas.

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I can see that A. De Grey does not believe in the decoupling of healthspan and lifespan. I think he's wrong. He needs to prove that and he simply assumes it "commonsensically" - "nobody who is healthy is going to die". 

 

Are you talking about being hit by a bus?  I don't get your argument.  Maybe its because you have a different definition of the word "healthy"?  Sure a person can APPEAR to be healthy and then drop dead, but they weren't actually healthy.  Often we may have no symptoms from an underlying health problem... plaque in arteries, amyloid proteins slowly build up in your organs, etc.  A person with plaque or amyloid accumulation is most definitely not "healthy" even if they feel fine, they are basically a ticking time bomb.

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We should be careful not to beg the question and "no true scotsman" the argument in a circular tautology. Otherwise we can say by definition anyone who dies (except for accidents) died because they were unhealthy. The very fact you died proves you were unhealthy - a rather absurd view, in which you could say that under that definition nobody is ever healthy and health is a meaningless concept as we're perpetually in a state of slow march to death as our "health" deteriorates from the moment of birth until it finally results in death. To take Aubreys argument "healthy and then suddenly you keel over dead" - umm, yes, that's exactly what happens when you die of natural causes or "old age" or your time is up. It is why a rat lives 4 years and a whale 200 years. It's not that the rat is very very sick and dies quickly (4 years) whereas the whale is very healthy and lives a long time (200 years) - nope, it's how the organism is built by design (actually random evolution, of course). If we imagine that there is a certain number of cell divisions and when you've run through those you die, then the problem is not that you suddenly got "sick", rather the deterioration is designed in, not a "sickness". In your analogy, if plaque or amyloid accumulation - or more generally senescent cell accumulation overwhelms the organism then that senescent cell accumulation is not a sickness, it is perfectly normal given the way the organism (or machine) had been designed - planned (or unplanned) obsolescence, whatever the outcome of evolution was. Our capacity to clear plaque, or senescent cells deteriorates with age, it's not a result of sickness - in other words, not all deterioration is the result of loss of health, humans have only been designed with a limited immune and repair capacity, and once that's gone, it's gone, due to design not sickness. The organism may be perfectly healthy for a 4 year old rat, it's just not meant to last beyond 4 years. If your car has a tank capacity of 400 miles and then stops, it's not because it broke, but because its tank was designed for no more than 400 miles. You can refill the gas or build in a bigger tank, but you can't say the original car broke down.

 

In other words, you can have a perfectly healthy human die at 60, 80, 100, 120, or whatever their genetic makeup allowed. You can also die of illness - you were meant to live till 80, but passed away at 30 as a result of a bad diet and heart attack. My point about lifespan and healthspan is that it's common to assume that they are the same - when clearly they are not. You can have two people with the genetic potential to live to 90 and both do, except one in ill health and disabled (though not so ill as to die from it) - both reach exactly the same age so lifespan is equal between them, but healthspan is not, as one spends the last 20 years disabled. To then say that the healthy one must have died because by definition they must not have been healthy is a tautology making the whole concept of health superfluous. 

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Tom, we pretty much know that cells have to be replaced en masse for effective rejuvanation.  Just because we can't do this today, doesn't mean we won't be able to in the future.  Heck we could conceivably one day transfer a brain into a whole new body, effectively replacing every cell at once except for the brain itself.  Of course that leaves the huge problem of how to rejuvenate the brain.  Expanding healthspan without lifespan is the "childs play" that Aubrey is constantly mocking as "thinking too small".  Sure, most of the big ideas are science fiction today, but the more people working on this, the more likely it will become reality.

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I have no objection to the idea of rejuvenation, and certainly hope it comes to fruition - who wouldn't! And I totally agree that we need forward thinkers and support to move this forward. Thinking "big" is good. I think it's doable, even if I also think that Aubrey vastly underestimates the difficulties involved. My objection is much more narrow - he explicitly conflates lifespan and healthspan, which I think is simply factually wrong. You can't take the big steps if you get the small steps wrong, and it begins with being accurate and precise in describing the world as it is. 

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Tom, you'll like this, the ultimate convolution of healthspan and lifespan, haha ;)

 

https://youtu.be/MjdpR-TY6QU

I'm sure you guys all know that there's a PR/marketing angle to this. The average person out there tends to get freaked out by the thought of radical life extension. So for Aubrey and other pro life extension authorities it's more effective to sell an agenda that's focused on increasing "health span".

 

It's all about having the right packaging to connect with a mass audience and build moment. If we can normalize an agenda that wants to address the root causes of the diseases of aging it's then not that much of a leap to attacking the more fundamental drivers of aging.. so I see this health span PR push as an incrementalism approach to activism

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Is Immortality Possible?

Another recent response (from LEAF) on this topic...

 

 

 

Yes there are some incredible data there, such as the fish and tortoise who exhibit centuries of life. Pls nt the greenland shark, reported to have reached 400 years, is a cold water species, maybe chronical cold exposure increases lifespan even more.

 

The hydra as far as I gathered is still a total enigma, sure introducing some of its genome into human genome might create an immortal human-hydra.  Or perhaps a monster...

 

Fantasy runs unchained by reading those data.

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Guest Steven Moo

It is good to have a keen group of people discussing this "human" issue : Death is part of life vs Immortality.

From my opinion, there is still a hope out there. It's the human duty to discover and uncover these mystery as everyone believe themselves that human claim to be the smartest in the planet.

I won't go into a topic where dead people become alive. But instead where aging people should become youthful. Todate, I am still performing self-study on the topic, and found out some interesting issue or puzzle which I hope to discover it one by one.

What things trigger me to look into this topic is our parents issue is actually ours issue. The genetic or how the way parents lives relates to us especially the way we think/talk and disease or cancer. In order to change it, we must think outside the box and use it to protect our whole family.

Puzzle one : You look 10 years younger / You look 10 years older / You should look at the age like that.

a) Human doesn't look into this by taking care of themselves, but rather taking care of the elders and young most of the time.

 

b) We live in the IT age, that we know we don't give 'unhealthy' food and drinks to the elders, but that 'unhealthy' food is consumed by ourselves and the young ones together.

 

c) People simply don't have the time to know and to take care where to start, everyone prefer instant answer.

d) People thinks their life is short. Get over it.

e) Elderly people are too slow, kids are too slow to be an adult also, that why we are busy.
I found these that human lives like that. One might start to realize that when we start to look at our friends at this age, some might look younger than us, and some might look older than us. Nothing happen next.

The solution is 'knowing' how to take care ourselves is the first step to discover the life path for both our young ones and to our old ones.

I have few puzzles are being discovered and still discovering few more. I hope i can help people to understand.

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