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Why Do We Advocate for Rejuvenation Research?


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#1 reason

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Posted 21 November 2014 - 11:02 PM


Yesterday, I had occasion to spend six hours or so in the emergency room of a medical center largely focused on treating serious conditions that are most prevalent in old people. A part of that experience by necessity involved listening to the comings, goings, and conversations of those present. These are not private places: they are typically divided visually by screens but with no way to avoid overhearing the staff and patients. The people there are generally not too concerned about privacy in the immediate sense in any case, having far more pressing matters to focus upon.

So, by proxy, one gets to experience small and somewhat wrenching slices of other people's lives. It is very easy for even those who follow aging research and speak up for rejuvenation treatments to forget just how hard it is to be very old. It's one thing to know about the catalog of pain, suffering, and loss of capabilities, the conditions we'd like to find ways to turn back, and another to watch it in action. It is, really, a terrible thing to be frail.

A fellow was brought in a little while after I arrived, a 90-something man who looked a lot better on the exterior than perhaps your mental picture of a 90-something individual might be. Tall, and surprisingly lacking in wrinkles stretched out on the rolling gurney under blankets, a mess of cables, and an oxygen mask. That he had had fallen was what I heard from the conversation of the medics, and was in pain. He cried out several times as he was moved from the gurney. It took some time and care to do it without hurting him more, given his weakness.

He seemed confused at first, but that was just my misperception: you try being 90 and in pain some time and see how well you do while you're being moved around and told to hold this and let go of that. The fellow answered the bevy of questions the receiving staff had for him, but the thing that caught at me was the time he took with the answers, and the questions he just missed. He was coherent, even quite sharp at times, not on any more painkillers than a handful of Tylenol, as I later heard, but he clearly struggled with something that we younger folk all take for granted: parse the question, find the information, form up a reply and speak it. Cognitive ability in all these areas becomes ever less efficient with old age, and there's something hollowing about hearing what is clearly a capable guy set back for a dozen seconds by a short question about one of the details of his fall. The medic repeated the question a few times and in different ways, which was clearly just making the information overload worse.

It sticks with you to be the observer in this situation and clearly and suddenly realize that one day that faltering older person will be you, trying and often failing to force your mind into the necessary connections rapidly enough for the younger people around you. I know this, but knowing it and having it reinforced by being there are two very different things. An aged person is no less intelligent, far more experienced, wiser and all the rest, but the damage to the structure of the brain that occurs even in those without dementia means that making use of all of that in the way it deserves is near insurmountable.

The fellow's 60-something daughter arrived a little later to provide support and fill in more of the details. A story was conveyed in bits and pieces: that he was near blind now, and just about too frail to walk safely, even with a frame. The blindness explained a great deal of what had sounded to my ignorant ears as confusion in the earlier part of the fellow's arrival: we assume all too many things about those around us, such as the use of sight in an unfamiliar environment, or the ability to walk, or think quickly - and all of this is taken from us by aging. The fellow lived with his wife still, and she was of a similar age to him. His wife was not there because she herself was too frail to be undertaking even a short trip at such short notice. That seemed to me a harsh blow on top of the rest of what old age does to you. At some point you simply cannot do everything you'd want to as a partner. You are on the sidelines and at the point at which your other half is most likely to die, you are most likely unable to be there.

In this case the fellow was in no immediate danger by the sound of it. By good luck this was in no way likely to be a fatal accident, but rather another painful indignity to be endured as a part of the downward spiral of health and ability at the end of life. Once you get to the point at which simply moving from room to room bears a high risk of accident, and this is by no means unusual for a mentally capable person in their 90s, then it really is just a matter of time before you cannot live for yourself with only minimal assistance.

When talking with his daughter while he waited on a doctor and medical assistants to come and go with tests and updates, the fellow was much faster in his responses, though this was interrupted by a series of well-meaning but futile attempts to ease his pain by changing his position, each as much an ordeal as the move from the gurney had been. The conversation between father and daughter had the sense of signposts on well-worn paths, short exchanges that recapitulated the high points of many discussions that had come before. She wanted her father to move into an assisted living facility, and this fall was the latest in a line of examples as to why it was past the time for this - she simply could not provide all of the support needed on her own. She wasn't even strong enough herself to be able to safely get him back up on his feet after a fall. He was concerned about cost and the difficulties of moving, uncertainties and change. They went back and forth on this for a while. "We have to accept that it's just going to be more expensive as we get older," she said at one point, and he replied "I think you're getting the picture now," and laughed. There wasn't much to laugh about, but we can all do it here and there under these circumstances. I believe it helps.

I walked out of there after my six hours of hurry up and wait was done. They were still there, and whenever it is he leaves to go home it is unlikely it will be on his own two feet. But this is a scene I'll no doubt be revisiting at some point in the future, some decades from now, playing the other role in this small slice of life. What comes around goes around, but I'd like it to be different for me, and more importantly to be different for millions of others a lot sooner than my old age arrives.

Which leads to this: why does Fight Aging! exist? Why do we do this? Why advocate, why raise funds for research programs into ways to treat aging that may take decades to pay off? We do this because we can help to create a future in which there will be no more emergency rooms like the one I visited, no conversations about increasing disability, no pain, and no struggles to answer questions as quickly as one used to. No profound frailty. All these things will be removed by the advent of therapies that can effectively repair the causes of aging, curing and preventing frailty and age-related disease, and the sooner this happens the more people will be spared.


View the full article at FightAging
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#2 Marios Kyriazis

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Posted 23 November 2014 - 11:20 AM

Good points. I agree if you are talking about dealing with the *causes* of aging, which is different from the SENS method which aims at the *effects* of aging. These are two different issues which need different methodologies.


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#3 Antonio2014

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Posted 23 November 2014 - 11:46 PM

Probably you are using a different definition of cause than Reason. The seven kinds of damage that SENS tries to repair cause other types of damage and eventually medical conditions like Alzheimer, strokes, atherosclerosis, etc. So, from that point of view, they are causes, not effects. OTOH, SENS seven kinds of damage are caused by the normal functioning of metabolism, that is not perfect and produces damage from time to time. So, from that other point of view, the metabolism is the cause and SENS damages are the effects.

 

But, since metabolism is much more complex than SENS damages, and we barely know how it works and even less how to adequately alter it, the logical approach is to directly repair the SENS damages, instead of trying to fix the metabolism (that will take us much more time and effort). Traditional research tries to fix the effects (Alzheimer, etc.) instead of their causes (SENS damages). In that sense, SENS tries to fix the causes instead of the effects that current medical practice tries to fix.


Edited by Antonio2014, 23 November 2014 - 11:49 PM.

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#4 Marios Kyriazis

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Posted 24 November 2014 - 10:53 AM

Probably you are using a different definition of cause than Reason. The seven kinds of damage that SENS tries to repair cause other types of damage and eventually medical conditions like Alzheimer, strokes, atherosclerosis, etc. So, from that point of view, they are causes, not effects. OTOH, SENS seven kinds of damage are caused by the normal functioning of metabolism, that is not perfect and produces damage from time to time. So, from that other point of view, the metabolism is the cause and SENS damages are the effects.

 

But, since metabolism is much more complex than SENS damages, and we barely know how it works and even less how to adequately alter it, the logical approach is to directly repair the SENS damages, instead of trying to fix the metabolism (that will take us much more time and effort). Traditional research tries to fix the effects (Alzheimer, etc.) instead of their causes (SENS damages). In that sense, SENS tries to fix the causes instead of the effects that current medical practice tries to fix.

 

 

It is true that there are different meanings of ‘cause’.

 

The fundamental cause of aging is rooted in evolutionary mechanisms which tend to sustain life for as long as possible even if this means the death of the individual, but the survival of the species. Let’s call this Cause A. This causes unequal distribution of resources which favour germline repairs instead of somatic repairs. Let’s call this cause B. This inequality of repair resources causes an inability to repair age-related damage. Let’s call this Cause C

 

So we have Cause A (inherently favouring the survival of germline)...causing B (taking repair resources away from the body)...which causes C (inability to repair damage). This, in turn, causes other events down the line such as those described by SENS and others. (Cause D)

 

And cause D results in physical age-related degeneration, loss of function and appearance of disease.

Conventional medicine aims at this final stage.

 

SENS aims at cause D. Some gerontologists aim at cause C. We, at ELPIs Foundation for Indefinite Lifespans aim at causes A and B.

 

If one aims at cause D only, ignoring the previous causes, then the effect of these other causes (A-C) will continue to operate indefinitely, negating any benefits derived from D.


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#5 Antonio2014

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Posted 24 November 2014 - 07:10 PM

If one aims at cause D only, ignoring the previous causes, then the effect of these other causes (A-C) will continue to operate indefinitely, negating any benefits derived from D.

 

 

Nope. SENS therapies aren't intended to be a one-time repair. They will be done from time to time. SENS doesn't stop aging, it removes part of it from time to time, like the maintenance of an old car. So the benefits aren't negated on the mid/long term, only in the short term. Also, SENS is not a complete set of anti-aging therapies, it will evolve in order to reach and maintain the escape velocity, incorporating new discoveries and techniques.


Edited by Antonio2014, 24 November 2014 - 07:15 PM.

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#6 Marios Kyriazis

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Posted 25 November 2014 - 08:05 AM

 

If one aims at cause D only, ignoring the previous causes, then the effect of these other causes (A-C) will continue to operate indefinitely, negating any benefits derived from D.

 

 

Nope. SENS therapies aren't intended to be a one-time repair. They will be done from time to time. SENS doesn't stop aging, it removes part of it from time to time, like the maintenance of an old car. So the benefits aren't negated on the mid/long term, only in the short term. Also, SENS is not a complete set of anti-aging therapies, it will evolve in order to reach and maintain the escape velocity, incorporating new discoveries and techniques.

 

You have stated some of the reasons why SENS has not been successful and why it will not work.

 

The worst example they came up with was the comparison of the human organism to an old car!! People who think that biological organisms are comparable to machines lack breath and depth of knowledge about how biology works.

 

As to the issue of clinical applications of rejuvenation biotechnologies see my recent posting here: https://www.linkedin...t-curing-ageing


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#7 Antonio2014

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Posted 26 November 2014 - 08:56 AM

You have stated some of the reasons why SENS has not been successful and why it will not work.

 

The worst example they came up with was the comparison of the human organism to an old car!! People who think that biological organisms are comparable to machines lack breath and depth of knowledge about how biology works.

 

 

Please, try to argue instead of only posting your opinion.

 

 


As to the issue of clinical applications of rejuvenation biotechnologies see my recent posting here: https://www.linkedin...t-curing-ageing

 

 


1. Problems with Stem Cell Therapies

 

Stem cell harvesting doesn't need to be done from the bone marrow. For example, the first clinical trial for a transplantation of iPSC was done from skin cells.

 

Also, the current trend in iPSC research is searching for ways to induce pluripotency in vivo instead of in vitro. In many cases, it has been found that the transplanted PSC aren't responsible for regenerating the tissue, but for changing the microenvironment and inducing the tissue own cells to regenerate it.

 

Of course, a costly and cumbersome procedure now doesn't need to (and most probably will not) be costly and cumbersome in the future.

 

 


2. Problems with Tissue Engineering

 

Same as above. Currently, engineered tissue is constructed outside the body and then surgically transplanted, but the next step in research is clearly regenerating tissues in vivo. See for example: https://www.fightagi...programming.php

 

 


3. Problems with Genetic Therapies

 

 


As a concept, gene therapy appears ideal in treating ageing changes. However, this is an oversimplification fraught with clinical obstacles. It is known there are several hundred genes that can modulate the ageing process.

 

SENS doesn't try to modify these genes at all.

 

 


Issues with pre-existing immunity to the vector, choice of vector, costs, dose, and many others need to be addressed. Non-viral vectors such as liposomes or methods based on nanotechnology need to be given to the patient via an intravenous route with all the problems discussed above. The new gene may not be inserted correctly on the DNA, or it may be overexpressed, causing more problems than it resolves. The risk of introducing infection or inducing a cancerous change remains.

 

For these and other reasons, the progress with gene therapy has not been as vigorous as expected. New techniques such as CRISPR cannot easily be applied in clinical situations involving humans. The current administration technique involves a hydrodynamic injection method which in mice has been proven effective in some experiments, but remains unusable in humans.

 

Again, you are assuming that current state-of-the-art technology will remain the same forever. I think this is the error that pervades all your discussion in your article, you assume that research will be frozen and technology will not evolve. It's like criticizing the internal combustion engine because the first car was slower than a horse. Technologies evolve and become better. They don't reach their maximum performance in the first year of application. For example, CRISPR was made to work on monkeys for the first time in January this year.


Edited by Antonio2014, 26 November 2014 - 09:53 AM.


#8 Marios Kyriazis

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Posted 26 November 2014 - 10:02 AM

 

Again, you are assuming that current state-of-the-art technology will remain the same forever. I think this is the error that pervades all your discussion in your article, you assume that research will be frozen and technology will not evolve. It's like criticizing the internal combustion engine because the first car was slower than a horse. Technologies evolve and become better. They don't reach their maximum performance in the first year of application.

 

 

 

Your comments are typical of people who support this approach (and I have seen hundreds of them- I been dealing with this subject for over 20 years). For instance, SENS have published peer review papers stating that they will use bone marrow transplants. When one criticizes this, they say oh no! we are not going to use BMT. They published peer-review papers about using pharmacological agents and enzymes. When one criticizes this, they say, oh no! we are not using pharmacological agents. And so on and on... 

 

When they run out of arguments, the standard reply is: "well, in the future, technologies will (we are sure) be advanced enough to provide the answer".  



#9 Antonio2014

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Posted 27 November 2014 - 08:48 AM

You haven't replied to any of my arguments, and (again) only stated an opinion (in this case, about me and other SENS supporters).



#10 corb

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Posted 27 November 2014 - 01:52 PM

 

When they run out of arguments, the standard reply is: "well, in the future, technologies will (we are sure) be advanced enough to provide the answer".  

 

 

Isn't that your philosophy though?

 

From your other article:

 

 

The message is clear: You have more chances of defying ageing if, instead of waiting for someone to discover a pill to make you live longer, you become a useful part of a wider network, and engage with a technological society. The evolutionary process will then ensure that you live longer-as long as you are useful to the whole.

 

So in your opinion, somehow evolution will start working on a decade per decade scale instead of a hundreds of centuries scale and and somehow evoke changes in our biology? Or maybe you mean the advancement of civilization and all technology is part of evolution so you encompass everything as part of evolution... but that can't be, seeing how you consider biotechnology not the answer, and any technological change to give us lifespan benefits will probably come from biotechnology or in compliance with biotechnology whether you like it or not.

 

Really, you're only exchanging the magical pill for the magical evolution. "just wait and it'll happen". You're not giving any plausible alternatives, biotechnology remains the best chance for a longer life right now and this will remain true for centuries to come.

And I'd like to point out something - the papers about enzymes and BMT posted by SENS were investigating technologies which are already widely used (although nowhere near the scale you want) that can be used in rejuvenation technologies. They're not supposed to be perfectly effective or massively widespread. They are meant to spearhead a proof of concept therapy that can show SOME rejuvenation in vivo.


Edited by corb, 27 November 2014 - 01:52 PM.

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#11 Mind

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Posted 27 November 2014 - 02:34 PM

 

 

You have stated some of the reasons why SENS has not been successful and why it will not work.

 

I think it unfair to say SENS has NOT been successful. They have only been going for a few years. They have done a lot with a meager budget and I am unsure if they have even had any clinical trials. Even if SENS does not cure aging, or is not the root cause of aging, there is at least a good chance the therapies will prove beneficial for many age-related maladies.


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#12 reason

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Posted 27 November 2014 - 02:41 PM

Of note: de Grey penned a response to Kyriazis at some point on criticisms of SENS, and apparently LinkedIn is a blog platform now?

 

https://www.linkedin...nse-to-kyriazis


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#13 Marios Kyriazis

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Posted 27 November 2014 - 06:49 PM

So in your opinion, somehow evolution will start working on a decade per decade scale instead of a hundreds of centuries scale and and somehow evoke changes in our biology? Or maybe you mean the advancement of civilization and all technology is part of evolution so you encompass everything as part of evolution... but that can't be, seeing how you consider biotechnology not the answer, and any technological change to give us lifespan benefits will probably come from biotechnology or in compliance with biotechnology whether you like it or not.

 

 

 

Really, you're only exchanging the magical pill for the magical evolution. "just wait and it'll happen". You're not giving any plausible alternatives, biotechnology remains the best chance for a longer life right now and this will remain true for centuries to come.

 

 

Don't confuse 'evolution by natural selection' with other types of evolution, such as, for example, artificial or intentional evolution. I am not talking about natural selection. Instead I am talking about directed evolution (directed by humans mind you, not by some sentient deity). Evolution means to successfully adapt to your environment and survive for as long as possible. That's all.  And I am not talking about some future development - this is my whole point. I am talking about mechanisms that can eliminate aging which are forced to operate now, this second.The very fact that you and others have been sharing' information that requires action' has a positive effect on your own aging, *now*, even while you are reading this. So, I am giving an alternative, and if one spends some time to comprehend it, it is also quite plausible, if not inevitable.

 

https://www.academia...y_somatic_cells



#14 Marios Kyriazis

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Posted 27 November 2014 - 06:55 PM

 

 

 

You have stated some of the reasons why SENS has not been successful and why it will not work.

 

I think it unfair to say SENS has NOT been successful. They have only been going for a few years. They have done a lot with a meager budget and I am unsure if they have even had any clinical trials. Even if SENS does not cure aging, or is not the root cause of aging, there is at least a good chance the therapies will prove beneficial for many age-related maladies.

 

The SENS concept has been going for over 20 years. The only success I see is with regards to advocacy and fundraising. If they have made any positive medically-applicable discoveries I am not aware of them. And I agree that biotechnologies will be very useful in age-related diseases (but not in eliminating aging as a process, i.e. not making us live significantly longer)



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#15 Antonio2014

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Posted 28 November 2014 - 09:33 PM

Since you persists on refusing to reply to my arguments, I stop posting here.


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