67 replies to this topic

[Antonio2014]

Sorry to say, but undue confidence in their own understanding of biology in general and aging in particular is the main characteristic of SENS and their supporters.

 

How about providing some refutation of what I posted instead of simply trying an ad hominem?

 

 

As for the link I posted, it was a "general public" version that should have prompted you to get interested in reading more on the subject. Then you would learn that the levels of all kinds of immune cells go down during prolonged fasting. This is what prompts the organism to regenerated them anew during the refeeding phase.

And, just in case you missed that part in your physiology studies, the newly created immune cells are generated in proportion to the current needed, iow with the emphasis on the ones that are required now -- as opposed to the ones that were necessary in the past to deal with a specific challenge. That's what generally causes a problem: the immune cells that linger in large quantities after the need for them is gone.

 

As I said, yo don't know SENS at all. Please read about it before judging it.

 

The T cells specialized in non dangerous viruses are maintained in high amounts because these viruses are allways present in the body (they can't all be killed). If you reduce the number of all T cells, they be regenerated by the bone marrow and, because the viruses are still present, you will end with the same proportion of useless T cells than before. What is needed is a therapy that preferently kills useless T cells, so that a healthy balance can be restored, and that is what SENS does.

Edited by Antonio2014, 21 November 2014 - 08:37 AM.

[corb]

But SENS don't even seem to be aware of these mechanisms and that's why they feel that they need to invent new ways to do their job. But in my view, all that needs to be done is to turn on or to upregulate the already existing repair functions. This appears to me like a more practical and realistic goal.

 

 

I'd like to point out, if a system is predetermined to fail and has evolved for hundreds of thousands of years with that program, it's very doubtful any of the mechanisms of self repair will be perfect, because there wont' be a need for them to be perfect - and they wouldn't have had the chance to evolve to perfection either way. The problem with programmed aging is not only the social connotation it will bring to the discussion but also the idea that upregulating the mechanisms already at work will be the best counteraction to aging - my biggest grime with it really, because in both the case of accumulated damage and programmed aging your own mechanisms of repair won't be ideal or sufficient. If anything in programmed aging damage will be used as a "clock" so the mechanisms might in fact be "purposefully" imperfect.

Programmed aging and accumulated damage are not contradictory. They are different sides of the same coin. In fact both theories complement each other when it comes to the ways you can counteract aging. If the system is following a predetermined path of failure, well that does not guarantee there is a path of success - in fact, there shouldn't be, even if it existed it would've been selected out a long time ago. Damage will happen regardless of the regulation of processes.

If the system simply can't keep up with damage because it's imperfect regardless of regulation ... well the result is the same. SENS remains a valid theoretical work in both cases because it attacks the damage directly.

 

I'd like to finish with this, as far as we know for the moment accumulated damage still makes more sense and is supported by more scientists working on aging and most researchers working with proteins, peptides, telomerase, etc like to point out their work is not geared to life extension in pretty much every interview they get FOR A REASON.

Take it for what it is.

[xEva]

As I said, yo don't know SENS at all. Please read about it before judging it.
 
The T cells specialized in non dangerous viruses are maintained in high amounts because these viruses are allways present in the body (they can't all be killed). If you reduce the number of all T cells, they be regenerated by the bone marrow and, because the viruses are still present, you will end with the same proportion of useless T cells than before. What is needed is a therapy that preferently kills useless T cells, so that a healthy balance can be restored, and that is what SENS does.

Let us just agree to disagree about our understanding of SENS. And as I personally part from a discussion with you, I'd like to inform you that the body is capable of getting rid of pretty nasty viruses, on its own, or with the help of drugs. Your belief that it is beneficial to preferentially kill the specialized immune cells, while the infection for which they are generated is still present, is the typical nonsense spewed by an ardent, testosterone-driven SENS supporter. Bye!

Edited by xEva, 21 November 2014 - 10:00 AM.

[xEva]

We can test this hypothesis.  If you are right, then the damage of aging will be very non-linear, and only start to accrue when the repair mechanisms fail.  However, this doesn't seem to be the case.  In the following paper, we find glycation increasing as a function of chronological age, so this form of damage accrual is linear.  As we get much older, various forms of damage might feed back on each other, causing a snowballing effect.

There is a little problem with cohort in the paper you cite. Why 'under 40'? As I recall, in another thread, when the same subject came up, you among others insisted that most people start showing the signs of aging at around 25. In this context, what relevance does this paper have to the discussion? If they showed the same for the cohort under 25 that would be more convincing (or pick whatever number at which you think the accumulated damage is still 'invisible'). Otherwise, this study only confirms what is already plainly seen.

Edited by xEva, 21 November 2014 - 10:29 AM.

[xEva]

@corb, I don't see why social connotations should influence one's preference for a theory attempting to describe how things work. In any case, it's irrelevant to the point I make. All I am saying is that repair mechanisms do exist and function fine until a certain age. It is only when they start failing that the damage we associate with aging begins to show. Perhaps for you the difference is only in semantics -? It's not for me. In this scenario, the cause of aging is not the stochastic damage from 'exposure to elements', which is a given for everything that exists in the Universe. Rather, aging is the failure of the existing repair mechanisms, which work quite well -- until a certain age.

A good illustration of this the picture of 2 kids with atypical progeria syndrome below. The girl is 16 and the boy 20. Compare them to any normal healthy 24-year old in your surrounding. Though a 24-y.o. should have sustained 50% more damage than the girl and 20% more than the boy, he/she still looks 'young' as a healthy 24-y.o. should, while, as you see, the girl on the picture looks like an average woman in her 50s or 60s and the boy like a 'healthy man' in his 70s.
 

 
These kids with progeria show that if 'acumulated damage remains invisible' that is only due to the functioning repair mechanisms and here is what happens when they don't work properly.

PS sorry for the picture, you can see a better version of it by clinking on it here

Edited by xEva, 21 November 2014 - 12:58 PM.

[Marios Kyriazis]

 

I agree with xEva about the inadequacy of SENS to provide viable solutions to aging. To be honest, I am amazed at how people still believe at the promise that SENS can deliver anything useful.

 

Apart from the technical and research issues, one of the most significant obstacles to their proposed therapies is translation (from laboratory research to clinical application). For example, a main therapy suggested by SENS is stem cell replacement through bone marrow transplant.  Currently, there are about 60 000 bone marrow transplants performed each year in the world. Experts believe that with adequate funding and development of facilities, our medical systems can cope with perhaps another 30 to 50 thousand. That's a total of 100 000 bone marrow transplants a year. In order to treat a mere 10% of humanity with SENS-inspired bone marrow transplants of stem cells, we need to reach 700 000 000 people. It doesn't make any sense (oops, excuse the pun!) 

 

 

If this is the best example of why SENS won't work, then it's even more likely to succeed than I thought.  First of all, they are not proposing to do bone marrow transplants.  Their ideas about dealing with cell atrophy are more sophisticated, and don't involve xenotransplants.  Whatever therapy we are considering, delivering it to the entire planet on Day 1 is not part of the plan, and has nothing to do with the validity of the therapy.  At this point in our history, we can't protect the entire population of the world from disease, starvation, war, mis-governance, or natural disaster.  That doesn't mean that our efforts to get better at all of those things are without merit.

 

If you want to cherry-pick the least plausible part of the entire SENS program, I suggest that you look at WILT.  However, that doesn't mean the rest of it can't be done.

 

My example is one of many and it is hardly the best. See here for the full version of my paper:

https://www.academia...ogical_barriers

 

You say they are not proposing to do bone marrow transplants. But in this paper they contradict you, confirming that bone marrow transplants are a method for delivering stem cells:

 

Zealley B, de Grey AD. Strategies for engineered negligible senescence. Gerontology. 2013;59(2):183-9.

 

In any case how do they propose to transfer whatever they are manipulating (cells, genes etc) from the outside to the inside of the human body?

 

For example, there is a lot of mention of tissue engineering. How do you put this engineered tissue inside the human body? I can’t see any other method apart from a surgical operation. Just to play with numbers again, consider that many surgeons are not able to perform transplants of tissues. How many operations can a surgeon perform in a day (in addition to their routine, existing workload)? How many new surgeons do we need in order to treat 10% of humanity, even over a 10 year period (70 000 000 people a year)? How many times do we need to repeat the operation on the same patient in order to replace another organ? What about follow up, risk of infection, debility, let alone cost? Any major operation involves pre and post treatment modalities which may take at least 2-3 months. If we target several other organs in the body, plus whatever method you think they can employ in order to deliver stem cells (if it is bone marrow transplant, you are looking at several months), and genetic therapies, and vaccines, and immunosuppression, and apoptosis-inducers and, and ...(let alone WILT)...… there won’t be enough months in the year for a patient to have the full treatments.

 

Niner, I followed your posts for several years now. You are intelligent and educated. If you were a fool I wouldn’t mind so much, but it is frustrating to see clever people falling for this simplistic trash. There is nothing sophisticated about SENS. It reminds me of 3-year olds playing at the beach with plastic buckets and spades, aiming to build a fully functioning skyscraper. It won’t happen.

Edited by Marios Kyriazis, 21 November 2014 - 02:34 PM.

[niner]

 

You misunderstand the scientific method.  Pretending a published result (that is consistent with results in other species, no less!) doesn't exist isn't the "scientific method", it's sticking your head in the sand.  A scientist would look at the result and think about it, then design experiments to replicate the original work and to test hypotheses that arise from it.

 

I hope everyone is helping to fund rejuvenative research through FightAging's Triple-Matched fundraiser.

 

 

You misundertand what I said (or the scientific method, I'm not sure). In science, experiments must be independently repeated and confirmed. A single experiment proves nothing. That is what I pointed out. Then you called that dogmatic, but actually it's only the scientific method. The dogmatic view is thinking that a single experiment proves something.

 

There is a lot of miscommunication between us.  I never said that a single experiment "proved" something, I said that it was dogmatic to pretend that it (and a collection of related papers that all point in the same direction) "doesn't exist".   A scientist would say "there's something interesting here, although it needs replication".  That is my position, and I've been peripherally involved with or helped to fund more than one attempt at replication.

[corb]

@corb, I don't see why social connotations should influence one's preference for a theory attempting to describe how things work. In any case, it's irrelevant to the point I make. All I am saying is that repair mechanisms do exist and function fine until a certain age. It is only when they start failing that the damage we associate with aging begins to show. Perhaps for you the difference is only in semantics -? It's not for me. In this scenario, the cause of aging is not the stochastic damage from 'exposure to elements', which is a given for everything that exists in the Universe. Rather, aging is the failure of the existing repair mechanisms, which work quite well -- until a certain age.

 

So why do they fail in your opinion?
All I've read on the subject, all theories, they all pretty much amount to the same thing : oxidative damage build up, mitochondrial damage build up, infectious agent damage build up, metabolic waste build up (you can read waste as damage for all intense and purposes), and in the case of programmed aging a build up of yet unknown factors (but the ones I just listed are as good candidates as any other) which down regulate (or damage whichever is your word of choice) your repair mechanisms. So in the end of the day, it is just semantics the more you dig into it.

 

It's not that hard to comprehend really, the thing that gets damaged and needs repair is your cells. The thing that repairs the damage is your cells. So it's not that otherworldly to consider the possibility that the repair mechanism suffers with the damage. Your stem cells aren't isolated from your metabolism, they're not isolated from oxidative or heat stress, they're in the same tissue that needs them to start repair. So why is it strange that they can get damaged as well? It's not.

We can go down to the cellular organelle level and it's the same deal. The mitochondria deals with apoptosis, the nucleus deals with signaling, so they should deal with the cell's health, but if one gets damaged so does the other. And if they get damaged they can manufacture ROS and misfolded proteins without regulation. So a damaged cell, can damage the cells around it. And so on.

 

It has not remained the prevailing theory for no reason. It's complex but it makes sense.

 

In the case of progeria we're looking at a genetically impaired repair mechanism, but that doesn't mean the repair mechanism is impaired in the same manner in aging. Why isn't there a genetic illness that makes people more long lived if it's a simple issue of regulation? There's dwarfs and there's giants, so why does this genetic deformity go only one way? One could argue centenarians are just that but ... really? Have you seen one? They look just as old as they're supposed to be.

[xEva]

So why do they fail in your opinion?

this is the proverbial million dollar question

Whether aging is due to the accumulating stochastic damage or failure of existing repair mechanism is not mere semantics, simply because, before a problem can be solved, it is essential to identify it correctly, don't you think?

..and while we don't know why the repair mechanisms start failing, your proposal that they themselves suffer damage looks simplistic and premature. The best available evidence so far points at the cellular environment (ex. heterochronic parabiosis and related experiments, where old cells placed in young environment start acting young again and vice versa). ..and of course it is well known that, in principle, a cell can repair any damage, within reason, otherwise countless generations of life would not be possible.

And no, I don't consider the prevailing aging theory complex. To me it looks utterly simplistic. It merely states the obvious, that the damage accumulates and, in SENS approach, offers to fix it in a variety of wacky ways that may seem cool only to uninitiated.

And i'm a bit taken aback by the questions you posed in the end, 'cause it does not look like you have given them much thought.

[to age or not to age]

 

 

Too many people spend their time in the futile search for something that works now, when they only thing that will do any good is to work on making the treatments that will work tomorrow.

 

That's easy for a young person to say.  Vince, who is in his eighties if I'm not mistaken, may have different priorities.

 

 

and nothing in this area can be demonstrated to approach calorie restriction and exercise in terms of benefits delivered

 

Perhaps true at the moment, as long as we ignore Baati.  I suppose that many prefer to consider a result to not exist until it's replicated in a different lab, and I guess that's one way to roll, but it seems to me to be dogmatic.  I would rather acknowledge the existence of the work and its consistency with a number of other less dramatic results that have been published over the years, while we wait for replication.

 

 

[to age or not to age]

I know VInce Giuliano quite well and sometimes stay with him and his wife when filming in Boston.

Vince and his sometime writing partner James Watson are very bright people.  His background is in physics,

speaks a half dozen languages.  Watson is a surgeon and theoretical researcher.

 

The point hear is that I he believes that advances are incremental, and thus should be taken advantage of.

Is aging programmed?  Vince comes down on the side that it is.  Others, especially Aubrey (who I know) 

feel it is the pathological accumulation of damage.  Both theories can be right and actionable.  Those

who think metabolism is simply too vast to intervene in may be overlooking that fact that there are major

pathways, mtor, sirtuin IGF etc, which when dialed, have a major impact on healthspan, and arguably, lifespan.

David Sinclair is in this camp.  He feels that if we change this or that major pathway, one at a time, we may still get somewhere. 

 

There are major issues of feedback loops, stem cells and epigenetics still to be probed, so I simply don't believe one approach is the "correct" approach. 

[Kalliste]

I'm one of those who think metabolism won't pay off. It will be expensive and produce marginal benefits. Or do we have example of some life-form that continues to flourish while cellular junk builds up in it?

[niner]

There is a little problem with cohort in the paper you cite. Why 'under 40'? As I recall, in another thread, when the same subject came up, you among others insisted that most people start showing the signs of aging at around 25. In this context, what relevance does this paper have to the discussion? If they showed the same for the cohort under 25 that would be more convincing (or pick whatever number at which you think the accumulated damage is still 'invisible'). Otherwise, this study only confirms what is already plainly seen.

 

Under 40 means from 0 to 40.  I don't have access to the full text, so I don't know the precise ages of their subjects, but it would be pretty easy for them to look at people from 18 on.  Children as young as 4 have been shown to have AGE damage via fluorescence measurement.

 

These kids with progeria show that if 'acumulated damage remains invisible' that is only due to the functioning repair mechanisms and here is what happens when they don't work properly.
 

 

Corb has already responded to this, and I think he's right, but I'll chip in- The most common form of progeria is caused by a very specific gene defect involving farnesylation of lamin A.   Several other "accelerated aging" diseases, like Werner Syndrome and XP involve specific defects in our numerous DNA repair systems.   It's very interesting that a single gene defect can recapitulate as much of the aging phenotype as these diseases do.    I suspect that at the molecular level, the damage seen in these diseases is not identical to the damage we see in the chronologically elderly.   This might be as simple as a buildup of senescent cells, which would poison the remaining healthy cells around them.  As it happens, of all the forms of damage that SENS considers, the buildup of senescent cells might be the easiest to fix, since there has been so much technology for directed cell killing that has come from cancer research.

[APBT]

 

There is a little problem with cohort in the paper you cite. Why 'under 40'? As I recall, in another thread, when the same subject came up, you among others insisted that most people start showing the signs of aging at around 25. In this context, what relevance does this paper have to the discussion? If they showed the same for the cohort under 25 that would be more convincing (or pick whatever number at which you think the accumulated damage is still 'invisible'). Otherwise, this study only confirms what is already plainly seen.

 

Under 40 means from 0 to 40.  I don't have access to the full text, so I don't know the precise ages of their subjects, but it would be pretty easy for them to look at people from 18 on.  Children as young as 4 have been shown to have AGE damage via fluorescence measurement.

 

 

FULL TEXT:  Glycation associated skin autofluorescence and skin elasticity are related to chronological age and body mass index of healthy subjects

[xEva]

Under 40 means from 0 to 40. I don't have access to the full text, so I don't know the precise ages of their subjects, but it would be pretty easy for them to look at people from 18 on. Children as young as 4 have been shown to have AGE damage via fluorescence measurement.

thanks APBT I also found it here: http://www.tara.tcd....e=1&isAllowed=y

Well, their cohort was "Healthy female volunteers ... who gave their informed, written consent" which implies that there were no children or minors. And in fact, the median age in their 2 studies was 43 ±13.9 and 47 ±8.7. - Relevance?

Regarding children showing damage, no one here argues that damage does not occur. The argument is that damage does not accumulate while the repair functions are working, which is usually assumed to be until about age 25.

 

Corb has already responded to this, and I think he's right, but I'll chip in- The most common form of progeria is caused by a very specific gene defect involving farnesylation of lamin A.   Several other "accelerated aging" diseases, like Werner Syndrome and XP involve specific defects in our numerous DNA repair systems.   It's very interesting that a single gene defect can recapitulate as much of the aging phenotype as these diseases do.    I suspect that at the molecular level, the damage seen in these diseases is not identical to the damage we see in the chronologically elderly.

Those two don't have the most common form of progeria. Someone suggested that it could be Werner syndrome, but from what I read on it, it does not fit the bill. No one knows with certainty why skin and muscles of these two aged so rapidly, only that this rare form of progeria superficially looks remarkably like 'normal aging'. That was my point bringing them in. But I see that True Believers die hard.

Here is the duo again, with top row showing the most typical form of progeria. Those kids rarely live past 13 and, as you can see, have a very distinct look. In fact, their skin looks 'young', which was not the case with the 16-y.o. girl. Her face began to sag already at age 2 or 3.

 

 

 

 

 

Edited by xEva, 21 November 2014 - 10:35 PM.

[niner]

Well, their cohort was "Healthy female volunteers ... who gave their informed, written consent" which implies that there were no children or minors. And in fact, the median age in their 2 studies was 43 ±13.9 and 47 ±8.7. - Relevance?

Regarding children showing damage, no one here argues that damage does not occur. The argument is that damage does not accumulate while the repair functions are working, which is usually assumed to be until about age 25.

The argument that there is no accrual of damage until around age 25 seems to be a "True Believer" argument, to use your term. Where's the evidence? Has someone measured glycation or UV damage and found them to not get worse over time prior to 25?
 

Corb has already responded to this, and I think he's right, but I'll chip in- The most common form of progeria is caused by a very specific gene defect involving farnesylation of lamin A.   Several other "accelerated aging" diseases, like Werner Syndrome and XP involve specific defects in our numerous DNA repair systems.   It's very interesting that a single gene defect can recapitulate as much of the aging phenotype as these diseases do.    I suspect that at the molecular level, the damage seen in these diseases is not identical to the damage we see in the chronologically elderly.

Those two don't have the most common form of progeria. Someone suggested that it could be Werner syndrome, but from what I read on it, it does not fit the bill. No one knows with certainty why skin and muscles of these two aged so rapidly, only that this rare form of progeria superficially looks remarkably like 'normal aging'. That was my point bringing them in. But I see that True Believers die hard.

Here is the duo again, with top row showing the most typical form of progeria. Those kids rarely live past 13 and, as you can see, have a very distinct look. In fact, their skin looks 'young', which was not the case with the 16-y.o. girl. Her face began to sag already at age 2 or 3.

Well, if we don't know what disease they have, then there really isn't much we can say about it. I don't see how it can be evidence for anything if we know nothing about it. We don't even know if they are the age they claim to be. The skin of the kids with typical progeria looks smooth, like it's not particularly glycated or UV-damaged. The two on the bottom look like they are heavily UV-damaged, which suggests something along the lines of XP or WS, although probably not exactly the same as either of them. Their hair still looks reasonably youthful, which wouldn't be the case in the well known progeroid syndromes. Do they have other health problems typical of elderly people? What does their skin look like where it's not exposed to the sun? Equally bad, or much better? These things would give some clues to the mechanism. I just don't see how the existence of a rare syndrome that results in wrinkly sagging skin is evidence that aging is programmed. I think it's just another case of a defective damage control mechanism or a gene defect that causes some new form of damage, like HGPS.

Edited by niner, 22 November 2014 - 04:36 AM.

[Antonio2014]

 

As I said, yo don't know SENS at all. Please read about it before judging it.
 
The T cells specialized in non dangerous viruses are maintained in high amounts because these viruses are allways present in the body (they can't all be killed). If you reduce the number of all T cells, they be regenerated by the bone marrow and, because the viruses are still present, you will end with the same proportion of useless T cells than before. What is needed is a therapy that preferently kills useless T cells, so that a healthy balance can be restored, and that is what SENS does.

Let us just agree to disagree about our understanding of SENS. And as I personally part from a discussion with you, I'd like to inform you that the body is capable of getting rid of pretty nasty viruses, on its own, or with the help of drugs. Your belief that it is beneficial to preferentially kill the specialized immune cells, while the infection for which they are generated is still present, is the typical nonsense spewed by an ardent, testosterone-driven SENS supporter. Bye!

 

 

Please, don't try to "inform" people about things you don't know at all.

 

From "Ending Aging":

 

 

Unfortunately, this model of fiscal and military discipline only works well for infections that can be totally eliminated from the body. It begins to break down when the body faces enemies that it can fight to a standstill but not quite wipe out entirely. One class of such enemies is viruses of the herpes family: not just the infections commonly called "herpes" (herpes simplex of the mouth or genitals), but also Epstein-Barr virus (the one that usually causes glandular fever), varicella zoster (which causes chicken pox), and most especially a little-known infection called cytomegalovirus (CMV). All these viruses can be beaten back enough to put an end to active, symptomatic disease, but they are never completely defeated. A few copies of the virus continue to lurk hidden in some hard-to-reach corner of the body, dormant and out of sight of the immune system, waiting for the day when the tissue or the body as a whole is in such a weakened state that they can flare up again. In fact, the very name "herpes" is taken from the Greek herpein, "to creep," in reference to their ability to sneak about the body while they await conditions favorable to their reactivation.

 

You may never have heard of CMV, even though the odds are good that you are carrying it (up to 85 percent of adults over the age of forty do). That's because CMV rarely causes a recognizable illness, even briefly: about half of those undergoing CMV infection or reactivation suffer no symptoms at all, while the other half are afflicted only with hard-to-diagnose, nonspecific complaints such as general malaise, fever, and sweats.

 

But new research is showing us how CMV (and probably some other viruses) can also cause serious long-term harm to those of us who only suffer mild and transient activation and reactivation of the virus. Because the body can never quite consolidate its victory against these viruses, anti-CMV memory cells get called up to active duty again and again, and over successive iterations they gradually begin to ignore the apoptotic signal that is supposed to scale back their forces at the cessation of hostilities. There are various theories as to why this might happen, but I think it's most likely to be part of a complex adaptation to protect us against uncontrolled cell division (i.e., cancer) in these cells. Whatever its origin, the inability to recall these veteran troops progressively weakens the immune system's ability to fight other infections, new or old. The iron limitations on the "immunological space" or "military budget" ensure that, when the body can't cull unneeded T cells specific to CMV or other infections, it has to make up the numbers with other immunological soldiers. As a result, the numbers of naive cells available to keep the body ready to face new threats, and of memory cells for other pathogens, dwindle to dangerously low levels.

 

Edited by Antonio2014, 22 November 2014 - 07:28 AM.

[Antonio2014]

There is a lot of miscommunication between us.  I never said that a single experiment "proved" something, I said that it was dogmatic to pretend that it (and a collection of related papers that all point in the same direction) "doesn't exist".   A scientist would say "there's something interesting here, although it needs replication".  That is my position, and I've been peripherally involved with or helped to fund more than one attempt at replication.

 

 

In your original post you said:

 

 

Perhaps true at the moment, as long as we ignore Baati.  I suppose that many prefer to consider a result to not exist until it's replicated in a different lab, and I guess that's one way to roll, but it seems to me to be dogmatic.  I would rather acknowledge the existence of the work and its consistency with a number of other less dramatic results that have been published over the years, while we wait for replication.

 

Clearly, you were talking about a non-replicated experiment, and calling people dogmatic for not accepting that a non-replicated experiment proves something.

[xEva]

The argument that there is no accrual of damage until around age 25 seems to be a "True Believer" argument, to use your term. Where's the evidence? Has someone measured glycation or UV damage and found them to not get worse over time prior to 25?

..lol Where's the evidence for what's invisible even to True Believers?

Has someone measured the degree of glycation or UV damage in the cohort <25 and found it get worse?

The lack of evidence for the accumulated damage is built up in your preferred definition of aging: 'damage accumulates and remains invisible until..'. I tend to believe my own eyes and when I don't see the evidence for what is claimed, I say it's not there.


 
 

Well, if we don't know what disease they have, then there really isn't much we can say about it. I don't see how it can be evidence for anything if we know nothing about it. ... I just don't see how the existence of a rare syndrome that results in wrinkly sagging skin is evidence that aging is programmed. I think it's just another case of a defective damage control mechanism or a gene defect that causes some new form of damage, like HGPS.

I never claimed that aging is programmed. It's you guys here have such heavy-duty blinders on that you don't see many alternatives to the accumulated damage theory. You can't even see what's obviously wrong with it. Hey you don't even believe your own eyes! This requires a pretty strong faith.

I will repeat this one more time: aging is plainly seen. And: the repair mechanisms exist and it is entirely due to them that we don't age at a much faster rate. That those mechanisms are upregulated when nutrients become scarce is also a known fact, and it is also supported by the direct observation --i.e. it's plainly seen-- that people look visibly rejuvenated after a fast or a stretch of CR.

Edited by xEva, 22 November 2014 - 03:17 PM.

[xEva]

Finally, niner, your insistence that damage is there, even when it's invisible, steers the discussion away from what really matters to most people here. And most people here will gladly swap their visible damage for the invisible kind, the reality of which you so tenaciously uphold.

According to you, 24-year-olds are already "damaged". And? What's not damaged then? Was it you or Mind who insisted not long ago that even newborns are born already 'damaged'. How useful are such 'exact' definitions here?

I say, it's pure demagoguery.

Edited by xEva, 22 November 2014 - 03:39 PM.

[xEva]

@Antonio2014: There is no need for you to quote from your Bible, 'cause just about everyone here has already read it. ..and I underlined the most striking problems in that quote:
 

Please, don't try to "inform" people about things you don't know at all.
 
From "Ending Aging":
 

Unfortunately, this model of fiscal and military discipline only works well for infections that can be totally eliminated from the body. It begins to break down when the body faces enemies that it can fight to a standstill but not quite wipe out entirely. One class of such enemies is viruses of the herpes family: not just the infections commonly called "herpes" (herpes simplex of the mouth or genitals), but also Epstein-Barr virus (the one that usually causes glandular fever), varicella zoster (which causes chicken pox), and most especially a little-known infection called cytomegalovirus (CMV). All these viruses can be beaten back enough to put an end to active, symptomatic disease, but they are never completely defeated. A few copies of the virus continue to lurk hidden in some hard-to-reach corner of the body, dormant and out of sight of the immune system, waiting for the day when the tissue or the body as a whole is in such a weakened state that they can flare up again. In fact, the very name "herpes" is taken from the Greek herpein, "to creep," in reference to their ability to sneak about the body while they await conditions favorable to their reactivation.
 
You may never have heard of CMV, even though the odds are good that you are carrying it (up to 85 percent of adults over the age of forty do). That's because CMV rarely causes a recognizable illness, even briefly: about half of those undergoing CMV infection or reactivation suffer no symptoms at all, while the other half are afflicted only with hard-to-diagnose, nonspecific complaints such as general malaise, fever, and sweats.
 
But new research is showing us how CMV (and probably some other viruses) can also cause serious long-term harm to those of us who only suffer mild and transient activation and reactivation of the virus. Because the body can never quite consolidate its victory against these viruses, anti-CMV memory cells get called up to active duty again and again, and over successive iterations they gradually begin to ignore the apoptotic signal that is supposed to scale back their forces at the cessation of hostilities. There are various theories as to why this might happen, but I think it's most likely to be part of a complex adaptation to protect us against uncontrolled cell division (i.e., cancer) in these cells. Whatever its origin, the inability to recall these veteran troops progressively weakens the immune system's ability to fight other infections, new or old. The iron limitations on the "immunological space" or "military budget" ensure that, when the body can't cull unneeded T cells specific to CMV or other infections, it has to make up the numbers with other immunological soldiers. As a result, the numbers of naive cells available to keep the body ready to face new threats, and of memory cells for other pathogens, dwindle to dangerously low levels.

There is no way I can impart on you the missing knowledge in one post, so I will only describe to you a guy I once saw while camping. That young guy lived on the campground, 'cause he did not have another home, and that was mainly because he had AIDS. He also had one of those 'harmless' herpes viruses, which you could plainly see on him: most of the left side of his body was covered in blisters.

Here is the moral of the story: when the immune cells cannot do their job -- for whatever reason, like in his case, because the AIDS virus destroyed most of them OR because they were 'preferentially killed' like SENS offers -- the herpes virus no longer needs to hide but infects all cells it can get with impunity.

That's why this SENS idea is not just wacky but plain stupid.

[niner]

 

There is a lot of miscommunication between us.  I never said that a single experiment "proved" something, I said that it was dogmatic to pretend that it (and a collection of related papers that all point in the same direction) "doesn't exist".   A scientist would say "there's something interesting here, although it needs replication".  That is my position, and I've been peripherally involved with or helped to fund more than one attempt at replication.

 

 

In your original post you said:

 

 

Perhaps true at the moment, as long as we ignore Baati.  I suppose that many prefer to consider a result to not exist until it's replicated in a different lab, and I guess that's one way to roll, but it seems to me to be dogmatic.  I would rather acknowledge the existence of the work and its consistency with a number of other less dramatic results that have been published over the years, while we wait for replication.

 

Clearly, you were talking about a non-replicated experiment, and calling people dogmatic for not accepting that a non-replicated experiment proves something.

 

 

How do you manage to get "proves something" out of "consider a result to not exist"?  You are distorting my position, either because we are attaching different meaning to the same words or because you just like to argue...
 

[niner]

The argument that there is no accrual of damage until around age 25 seems to be a "True Believer" argument, to use your term. Where's the evidence? Has someone measured glycation or UV damage and found them to not get worse over time prior to 25?

..lol Where's the evidence for what's invisible even to True Believers?

Has someone measured the degree of glycation or UV damage in the cohort <25 and found it get worse?

The lack of evidence for the accumulated damage is built up in your preferred definition of aging: 'damage accumulates and remains invisible until..'. I tend to believe my own eyes and when I don't see the evidence for what is claimed, I say it's not there.
'

There has been a fair amount of work looking at UV damage in people of various ages, some as young as toddlers. Sunburns during childhood increase you risk for melanoma as an adult. (i.e., there is lasting damage) If damage accrual worked the way you think it does, I think there would be ample evidence to that effect by now. If you only believe what you can see with your eyes, can we take it that you do not believe in atoms? They are invisible. My definition of aging doesn't contain the word "invisible". Damage can be detected, just like atoms and molecules can. If you look closely, you can even see it with your eyes, if you know what to look for. Childrens' skin coarsens over time, and wrinkling begins well before 25 if a person is light complected and abuses their skin.

Well, if we don't know what disease they have, then there really isn't much we can say about it. I don't see how it can be evidence for anything if we know nothing about it. ... I just don't see how the existence of a rare syndrome that results in wrinkly sagging skin is evidence that aging is programmed. I think it's just another case of a defective damage control mechanism or a gene defect that causes some new form of damage, like HGPS.

I never claimed that aging is programmed. It's you guys here have such heavy-duty blinders on that you don't see many alternatives to the accumulated damage theory. You can't even see what's obviously wrong with it. Hey you don't even believe your own eyes! This requires a pretty strong faith.

I will repeat this one more time: aging is plainly seen. And: the repair mechanisms exist and it is entirely due to them that we don't age at a much faster rate. That those mechanisms are upregulated when nutrients become scarce is also a known fact, and it is also supported by the direct observation --i.e. it's plainly seen-- that people look visibly rejuvenated after a fast or a stretch of CR.

 
And I never claimed that repair mechanisms don't exist for many forms of damage. Unfortunately, they just aren't adequate in all cases. We don't have a mechanism to remove 7-ketocholesterol from lysosomes. We don't have an adequate mechanism to remove glucosepane crosslinks from the collagen molecules in the ECM. This is the kind of stuff SENS is working on. I know that fasting and CR are beneficial, but if you could get rid of skin damage that way, everyone would be doing it. Neither of those will eliminate serious wrinkles.

Finally, niner, your insistence that damage is there, even when it's invisible, steers the discussion away from what really matters to most people here. And most people here will gladly swap their visible damage for the invisible kind, the reality of which you so tenaciously uphold.

According to you, 24-year-olds are already "damaged". And? What's not damaged then? Was it you or Mind who insisted not long ago that even newborns are born already 'damaged'. How useful are such 'exact' definitions here?

I say, it's pure demagoguery.

You are looking at things in black and white, like a person is either "aged" or they aren't. That's just not how it works. You start accruing damage in utero, and it keeps getting worse. First it's invisible to the naked eye but can be seen with appropriate instruments. The you see it a little bit, then more, then more, and eventually you are elderly and you look like hell. If you don't see things in shades of grey, you will never understand this.

Please stop throwing around terms like demagoguery. That's kinda ad hominem, and is wrong anyway.

[xEva]

You are looking at things in black and white, like a person is either "aged" or they aren't. That's just not how it works.

-?! We must misunderstand each other. To me it looks the other way around. While I say, <25 is young and => 'undamaged', you say, damage starts in utero, and only because I cannot see it with a naked eye, it does not mean it's not there.

And to qualify your statement you go into molecules and atoms (!). Is that how you define damage in accumulating damage theory, seriously? See, that's the reason I thought your arguments were pure demagoguery. I never thought you actually meant it.

But pray why stop at atoms and molecules, if one can always go further and examine each atom separately and claim that this one, for example, has two of its orbitals overly excited, which may cause it to lose an electron or, god forbid, steal one from another molecule ..any moment now! look, it's happening! eww that's damage!

Indeed, how do you define 'undamaged' and is there such thing in principle? (in biology, out of all things)

Edited by xEva, 23 November 2014 - 02:32 AM.

[niner]

Well, xEva, I guess you are not a scientist. Yes, we define damage at the molecular level. That's the only way to understand it in such a way that you can do something about it. I guess you are defining damage as something you can see with your eyes. That's fine, but you aren't qualified to comment on SENS if you don't understand aging at the molecular level. You don't have to support it if you don't want to, but you shouldn't be calling it "wacky" or "stupid". I think you just don't understand what SENS is all about.

[xEva]

oh this is getting interesting! Let me understand more. But first, I'd like you to answer: How do you define 'undamaged' in biology?

And is it true then that undamaged perfection --on the atomic level!-- is your and SENS holy grail? Is that what you're aiming at when you say that you want to stop aging?

Also, I'd like you to qualify: in your definition of damage, are the animals with negligible senescence 'damaged'?

Sorry for all these questions, but I'm sure that others would also like to hear the answers, to form a better idea of what SENS is all about.

Then, re you not approving of me calling SENS idea to 'preferentially kill' T-cell that specialize in herpes viruses stupid, would you please elucidate its wisdom, 'cause, as I pointed out earlier, this should cause the virus to not just flare up but to practically take over the host, as indeed I once saw. This, in my book, is not a favorable outcome. How would this strategy benefit the host?

Thanks niner!

Edited by xEva, 23 November 2014 - 04:37 AM.

[Kalliste]

I'm not sure what you are trying to say xEva. Maybe you could elaborate your own theory of aging in a short summarized form?

 

To me it seems we age partially as a biological program and part as accumulated damage.

I'm not sure what percent of each is responsible for what, and I'm sure both processes run in parallell and probably interfer and run feedback loops with each other in various weird ways that will take a long time to figure out and map.

 

Repair seems like the best approach. Throw in some physícal activity, CR and fasting right now to increase odds of being alive when/if we can fix aging.

[Antonio2014]

@Antonio2014: There is no need for you to quote from your Bible, 'cause just about everyone here has already read it. ..and I underlined the most striking problems in that quote:
 

There is no way I can impart on you the missing knowledge in one post, so I will only describe to you a guy I once saw while camping. That young guy lived on the campground, 'cause he did not have another home, and that was mainly because he had AIDS. He also had one of those 'harmless' herpes viruses, which you could plainly see on him: most of the left side of his body was covered in blisters.

Here is the moral of the story: when the immune cells cannot do their job -- for whatever reason, like in his case, because the AIDS virus destroyed most of them OR because they were 'preferentially killed' like SENS offers -- the herpes virus no longer needs to hide but infects all cells it can get with impunity.

That's why this SENS idea is not just wacky but plain stupid.

 

 

I'm getting bored of your stupid comments about Bibles and lack of knowledge of people that present arguments you can't refute or simply you don't read (like the first link I posted). I can't see any refutation on your answer, so my reply finish here.

Edited by Antonio2014, 23 November 2014 - 11:04 PM.

[Antonio2014]

 

 

There is a lot of miscommunication between us.  I never said that a single experiment "proved" something, I said that it was dogmatic to pretend that it (and a collection of related papers that all point in the same direction) "doesn't exist".   A scientist would say "there's something interesting here, although it needs replication".  That is my position, and I've been peripherally involved with or helped to fund more than one attempt at replication.

 

 

In your original post you said:

 

 

Perhaps true at the moment, as long as we ignore Baati.  I suppose that many prefer to consider a result to not exist until it's replicated in a different lab, and I guess that's one way to roll, but it seems to me to be dogmatic.  I would rather acknowledge the existence of the work and its consistency with a number of other less dramatic results that have been published over the years, while we wait for replication.

 

Clearly, you were talking about a non-replicated experiment, and calling people dogmatic for not accepting that a non-replicated experiment proves something.

 

 

How do you manage to get "proves something" out of "consider a result to not exist"?  You are distorting my position, either because we are attaching different meaning to the same words or because you just like to argue...
 

 

 

 

I will quote a more complete text of your first post:

 

 

 

and nothing in this area can be demonstrated to approach calorie restriction and exercise in terms of benefits delivered

 

Perhaps true at the moment, as long as we ignore Baati.  I suppose that many prefer to consider a result to not exist until it's replicated in a different lab, and I guess that's one way to roll, but it seems to me to be dogmatic.  I would rather acknowledge the existence of the work and its consistency with a number of other less dramatic results that have been published over the years, while we wait for replication.

 

 

The first poster talked about "can be demostrated". You replied that you "suppose that many people prefer to consider a result to not exist until it's replicated" and called that people dogmatic. So, since you replied to that statement about demonstrations, I understand that you consider that there is a demonstration even when there is only one result, and people that disregard that one result as irrelevant are dogmatic.

[xEva]

I'm not sure what you are trying to say xEva. Maybe you could elaborate your own theory of aging in a short summarized form?
 
To me it seems we age partially as a biological program and part as accumulated damage.
I'm not sure what percent of each is responsible for what, and I'm sure both processes run in parallell and probably interfer and run feedback loops with each other in various weird ways that will take a long time to figure out and map.
 
Repair seems like the best approach. Throw in some physícal activity, CR and fasting right now to increase odds of being alive when/if we can fix aging.

Yours is a sensible approach. As for me, I don't have a preferred aging model at the moment. I was merely pointing out the obvious problems with the accumulated damage theory and SENS approach to it.

..and it's too bad niner did not answer my questions, cause in the process he would see the fallacy of his 'scientific' molecular approach. It can only be applied to a singular cell, maybe -- but certainly not to a multicellular organism. There is no such thing as a 'molecularly perfect' metazoan. Life is messy. At any given moment cells get damaged, die and are replaced. And talking about skin! this is especially true of epithelia, which are continuously shed.

I'm sorry to say, but all SENS 'strategies' are mere geek fantasies. And they could be cool, if they were based on reality of how an organism really works. But no! Like Antonio here demanding 'to refute'. No amount of 'refuting' will substitute a course in physiology.

And regarding you hopes:

"and I'm sure both processes run in parallell and probably interfer and run feedback loops with each other in various weird ways that will take a long time to figure out and map."

according to the current state of knowledge of nonlinear logical processes, "to figure out and map" them is impossible in principle. But that was the point Michael Rose made many years ago, when he said that reductionist approach to biology was scientifically invalid. So good luck to all would be scientists here refuting it

Edited by xEva, 24 November 2014 - 03:13 AM.