23 replies to this topic

[MikeGore]

When TA-65 and Isagenix came out, the attitude and optimism that they were talking with made it sound like an anti-aging miracle had been found. They keep going on and on about the science. They are in love with it. But explaining and re-explaining the theory with such enthusiasm doesn't mean it works.

What is my definition of an anti-aging miracle?

If you can take a 80 year old man and make him look like he is 50 years old, that would be a miracle.
If you can take a 60 year old man and make him look like his is in his late 30s.

So even though so much hype is being put on these products with a ridiculously expensive price tag, they are not doing what people are hoping for.

I mean I watched a video of the Isagenix founders and formulators talking, why do they still have grey hair or baldness?

Most definitely being the owner of company gotta have some perks such as consuming more than you could put down your throat at zero cost.

So where is the full set of colored hair? Where is the youthful looking face?

And why is it that we can not find any information on the internet on the date of birth of these people.

How old are John Anderson, Bill Andrews, Ed Park. These are important questions, because if it is not working for them, it won't work for anybody else.

Edited by MikeGore, 25 April 2013 - 05:56 PM.

[zorba990]

IMO Telomerase will do little to reverse such conditions. True AGE breakers and stem cell therapies might

[sthira]

Mike, these are all good questions and you write what I think, too, and why I don't fall for their products, either.

[YOLF]

Still hoping for a legit anti-aging product myself. Though reversing balding will require more than an anti aging pill, the hair follicle cells have died off and skin cells or what ever have taken up the real estate, so stem cell therapy will be required in these cases. TA-65 and similar are just part of the puzzle as they say, so supporting them is important, but they are definitely hyped up.

[Methos000]

Ed Park was born on 7/30/1967.

Bill Andrews was born 12/10/1951.

I don't know about John Anderson, but it's likely that he's older than Bill.

Edited by Methos000, 25 April 2013 - 09:55 PM.

[niner]

Guys, none of the telomerase guys have actually claimed that TA-65 or any of the others will perform the kind of anti-aging miracles that the OP mentions. They all left that up to your imaginations, and in most cases, that was all they needed to do. Zorba990 has it right. Telomere lengthening alone isn't going to reverse the kind of damage mentioned above. That doesn't mean it doesn't do some very useful things, particularly for the aging immune system. There is a hell of a lot of misdirection and near-deception swirling around the telomerase activator space, not to mention what I might charitably call gross self-deception on the part of vendors, or what I might call outright fraud when in a more cynical mood.

[Methos000]

IF we had an intervention which could maintain telomeres at their optimum lengths, the Strong Telomere theory of aging maintains that such 'miracles' could occur. The theory predicts that the robust repair mechanisms in the young human body are gradually abandoned due to changes in gene expression due to relative loss of telomere length, aka the telomere position effect. Genes at the ends of the chromosome nearest the telomeres are turned on as the telomere erodes, and silenced if the telomere is lengthened again via telomerase. Cellular senescence is thus not the only consequence of telomere loss. TA-65 is not such an intervention, unfortunately. It is only a weak inducer of telomerase, and only has access to lengthen the telomeres which are already critically short. A structure in telomeres called the d-loop is closed in telomeres which are not yet critically short, and prevents telomere maintenance via the pathway used by TA-65. Mind you, this theory has not yet been shown to be correct. It has a fair amount of supporting evidence though, and has not yet been disproven either.

http://www.sciencema.../5524/2075.full

[hav]

IF we had an intervention which could maintain telomeres at their optimum lengths, the Strong Telomere theory of aging maintains that such 'miracles' could occur. The theory predicts that the robust repair mechanisms in the young human body are gradually abandoned due to changes in gene expression due to relative loss of telomere length, aka the telomere position effect. Genes at the ends of the chromosome nearest the telomeres are turned on as the telomere erodes, and silenced if the telomere is lengthened again via telomerase. Cellular senescence is thus not the only consequence of telomere loss. TA-65 is not such an intervention, unfortunately. It is only a weak inducer of telomerase, and only has access to lengthen the telomeres which are already critically short. A structure in telomeres called the d-loop is closed in telomeres which are not yet critically short, and prevents telomere maintenance via the pathway used by TA-65. Mind you, this theory has not yet been shown to be correct. It has a fair amount of supporting evidence though, and has not yet been disproven either.

http://www.sciencema.../5524/2075.full

If I'm understanding that 2001 study correctly they used a plasmid to manually break off pieces of chromosomes at different positions and then drew conclusions, which I don't get, about which breakage locations are able to better grow new telomeres.

We seeded de novo telomere formation in (telomerase-positive) HeLa cells by introducing a linear plasmid containing a luciferase reporter adjacent to 1.6 kb of telomere repeats (Web fig. 1) (11). Integration of a repeat containing plasmid can result in breakage of the chromosome, followed by extension of the plasmid telomeric sequences by telomerase and loss of the distal chromosome fragment

Wouldn't the net result be a mutation? Might be of concern if the plasmid/chromosome-breaking methodology they employed could spontaneously occur within the body.

Howard

Edited by hav, 26 April 2013 - 05:29 PM.

[niner]

IF we had an intervention which could maintain telomeres at their optimum lengths, the Strong Telomere theory of aging maintains that such 'miracles' could occur. The theory predicts that the robust repair mechanisms in the young human body are gradually abandoned due to changes in gene expression due to relative loss of telomere length, aka the telomere position effect. Genes at the ends of the chromosome nearest the telomeres are turned on as the telomere erodes, and silenced if the telomere is lengthened again via telomerase. Cellular senescence is thus not the only consequence of telomere loss. TA-65 is not such an intervention, unfortunately. It is only a weak inducer of telomerase, and only has access to lengthen the telomeres which are already critically short. A structure in telomeres called the d-loop is closed in telomeres which are not yet critically short, and prevents telomere maintenance via the pathway used by TA-65. Mind you, this theory has not yet been shown to be correct. It has a fair amount of supporting evidence though, and has not yet been disproven either.

http://www.sciencema.../5524/2075.full

I'd never even heard of the Strong Telomere Theory of Aging, but managed to find this ancient interview from LEF that talks about it. It sounds like it's a hypothesis, not a theory, and something tells me that there's no evidence to support it.

That's very interesting about TA-65 only extending critically short telomeres. I thought that TA-65 was a telomerase inducer that caused expression of the telomerase complex. What you're saying here sounds like TA-65 interacts with existing telomerase in a way that only works for critically short telomeres. This implies that the telomerase RT Complex is already ready and waiting, but that it just can't deal with the short telomere on its own. That doesn't seem right though, because if it was already present and functional, shouldn't it be lengthening at least the telomeres that were long enough? I must be missing something.

[bsm]

It is only a weak inducer of telomerase, and only has access to lengthen the telomeres which are already critically short. A structure in telomeres called the d-loop is closed in telomeres which are not yet critically short, and prevents telomere maintenance via the pathway used by TA-65. Mind you, this theory has not yet been shown to be correct. It has a fair amount of supporting evidence though, and has not yet been disproven either.

http://www.sciencema.../5524/2075.full

ie extendible and nonextendible states
http://www.ncbi.nlm....pubmed/15109493

[Mind]

I recently interviewed Bill Andrews and there will be another interview available shortly with Preston Estep (about telomere biology/testing).

Bill mentioned a couple of recent mouse studies that showed very good data.......in mice.

My novice view is that telomere maintenance could be a moderate benefit for health and longevity. Aging is complex and it would be a surprise to me if this one intervention would prove to be a "holy grail" or "silver bullet" against aging. One thing telomere maintenance would not seem to address is the accumulation of indigestible aggregates (glucosepane and lypofuscin, for example). These accumulate throughout life, the body does not get rid of them when you are young (with long telomeres) or old (with short telomeres).

[niner]

It is only a weak inducer of telomerase, and only has access to lengthen the telomeres which are already critically short. A structure in telomeres called the d-loop is closed in telomeres which are not yet critically short, and prevents telomere maintenance via the pathway used by TA-65. Mind you, this theory has not yet been shown to be correct. It has a fair amount of supporting evidence though, and has not yet been disproven either.

http://www.sciencema.../5524/2075.full

ie extendible and nonextendible states
http://www.ncbi.nlm....pubmed/15109493

Wow, this concept of extendible and nonextendible states is a pretty big deal. It means that we've been using the wrong figure of merit for the past 5 years. Average telomere length isn't going to be responsive to telomerase, or at least it will hardly be responsive. The correct thing to look at is the fraction of critically short telomeres. In one of the human TA-65 papers, it was mentioned that the fraction of critically short telomeres improved. The next question is how long does the telomere need to be in order to see the Telomere Position Effect discussed in Methos000's link? Can telomerase get the telomere to that length, or will telomerase just keep the length from getting critically short?

Ed Park's claim: "My telomeres are now as healthy as a teenagers!" after years of TA-65 use now sounds a little questionable. I wonder what he bases that on?

[Methos000]

It is a hypothesis in the strict use of the terms 'theory and 'hypothesis'. Many of us on this site discuss this and that 'theory' of aging (see the forum here titled 'Aging Theories'), where we have many competing 'theories' most of which have no more supporting evidence than the one to which I referred. So, I'm guilty of following common (non-scientific) usage.

Dr. Michael Fossel (who was interviewed in the LEF article) laid out the case for the Telomere Hypothesis in his books 'Cells, Aging and Human Disease' and 'Reversing Aging'.

As he said, the weak hypothesis 'that telomere shortening is associated with and times the onset of cellular senescence' is well accepted and noncontroversial. It approaches theory status where cellular aging is concerned.

The strong hypothesis "that telomere shortening ultimately times the onset and progression of organismal [whole body] aging. Again, it doesn't cause aging, it times the onset and progression of aging" is currently less accepted. It's supported by the existence of eukaryotic organisms which are believed to exhibit negligible senescence (lobsters, rainbow trout, Aldebra giant tortoise, The Rougheye rockfish, etc.) Several of these species have been studied and found to express telomerase throughout their somatic cells. If all of the SENS strategies are actually necessary to achieve NS, it's truly remarkable that all these species managed to independently evolve numerous mechanisms to successfully fight all these multiple causes of aging. The existence of NS species pretty much dooms the 'wear and tear' and 'entropy' hypotheses.

http://www.scribd.co...-Telomerase-Expression

http://onlinelibrary...0398.x/abstract


It appears that you've already found a more detailed explanation of the telomere capped/uncapped states as they relate to telomerase activity.

IF we had an intervention which could maintain telomeres at their optimum lengths, the Strong Telomere theory of aging maintains that such 'miracles' could occur. The theory predicts that the robust repair mechanisms in the young human body are gradually abandoned due to changes in gene expression due to relative loss of telomere length, aka the telomere position effect. Genes at the ends of the chromosome nearest the telomeres are turned on as the telomere erodes, and silenced if the telomere is lengthened again via telomerase. Cellular senescence is thus not the only consequence of telomere loss. TA-65 is not such an intervention, unfortunately. It is only a weak inducer of telomerase, and only has access to lengthen the telomeres which are already critically short. A structure in telomeres called the d-loop is closed in telomeres which are not yet critically short, and prevents telomere maintenance via the pathway used by TA-65. Mind you, this theory has not yet been shown to be correct. It has a fair amount of supporting evidence though, and has not yet been disproven either.

http://www.sciencema.../5524/2075.full

I'd never even heard of the Strong Telomere Theory of Aging, but managed to find this ancient interview from LEF that talks about it. It sounds like it's a hypothesis, not a theory, and something tells me that there's no evidence to support it.

That's very interesting about TA-65 only extending critically short telomeres. I thought that TA-65 was a telomerase inducer that caused expression of the telomerase complex. What you're saying here sounds like TA-65 interacts with existing telomerase in a way that only works for critically short telomeres. This implies that the telomerase RT Complex is already ready and waiting, but that it just can't deal with the short telomere on its own. That doesn't seem right though, because if it was already present and functional, shouldn't it be lengthening at least the telomeres that were long enough? I must be missing something.

[niner]

It's supported by the existence of eukaryotic organisms which are believed to exhibit negligible senescence (lobsters, rainbow trout, Aldebra giant tortoise, The Rougheye rockfish, etc.) Several of these species have been studied and found to express telomerase throughout their somatic cells. If all of the SENS strategies are actually necessary to achieve NS, it's truly remarkable that all these species managed to independently evolve numerous mechanisms to successfully fight all these multiple causes of aging. The existence of NS species pretty much dooms the 'wear and tear' and 'entropy' hypotheses.

http://www.scribd.co...-Telomerase-Expression

http://onlinelibrary...0398.x/abstract

Are these animals really negligibly senescent, as in not having their mortality risk go up with advanced age? It just doesn't seem like this could be right, or at least it wouldn't translate to mammals. I think these animals probably have relatively low rates of aging- why wouldn't they eventually end up loaded with lipofuscin, aggregated proteins, crosslinks, and other junk? Even the authors of the lobster paper seem to agree with this, saying:

But clearly, ageing is a multifactorial process and should not be reduced to cellular replicative senescence.

Surely the SENS people are aware of these species. If telomerase expression was all that was needed to achieve NS in a human, I think they'd be on top of it.

[Methos000]

At least some researchers believe that they are negligibly senescent according to that definition. If indeed they turn out not to be NS, I'd like to know was much as anyone else. We could then turn our attention to supporting other fruitful lines of research.

Bill Andrews belongs to the school of thought that telomeres have the 'shortest fuse' in the collection of possible 'time bombs' that prevent NS status in humans. Addressing telomere erosion would be necessary, but perhaps not sufficient to achieve NS. Perhaps lipofuscin, aggregated proteins, crosslinks, and other junk would still stand in our path after the telomere issues are solved (If the recipe for NS in the lobster, etc. does not translate to mammals).

I recall reading that Aubrey de Grey described the strong telomere hypothesis as 'not disproven' at one point. He also mentioned that some differentiated cells (such as neurons and cardiac tissue ) do not divide, and thus their telomeric status is irrelevant. Michael Fossel points out that those types of cells all depend on other cells that do divide, such as neurons requiring the presence of glial cells in the brain. Possibly de Grey has a stronger objection that I have not heard...?


http://www.programme...senescence.html

http://en.wikipedia....ible_senescence this one has some citations.

Edited by Methos000, 29 April 2013 - 09:56 PM.

[niner]

At least some researchers believe that they are negligibly senescent according to that definition. If indeed they turn out not to be NS, I'd like to know was much as anyone else. We could then turn our attention to supporting other fruitful lines of research.

Bill Andrews belongs to the school of thought that telomeres have the 'shortest fuse' in the collection of possible 'time bombs' that prevent NS status in humans. Addressing telomere erosion would be necessary, but perhaps not sufficient to achieve NS. Perhaps lipofuscin, aggregated proteins, crosslinks, and other junk would still stand in our path after the telomere issues are solved (If the recipe for NS in the lobster, etc. does not translate to mammals).

Maybe the thing to do would be to look at redox damage, aggregates, crosslinks etc in the NS species to see how those things are handled and how much of a problem they are. I know that some of this, for example in the naked mole rat, has been done. I wouldn't call the naked mole rat NS, but it is unusually long-lived for its size. Bill is pretty single-minded regarding telomeres, but I'd like to hear his reasoning behind the "shortest fuse" idea. If telomeres are the main reason for cells to become senescent, then maybe that's it, since we know senescent cells are little toxin factories that cause all manner of problems.

[Methos000]

Are we certain that no endogenous repair mechanism exists for lipofuscin and AGEs? This page suggests such a mechanism for lipofuscin in rats:
http://en.wikipedia....wiki/Lipofuscin


Even glucosepane can be removed via extracellular matrix turnover according to this article: http://en.wikipedia....iki/Glucosepane

As an aside, It's interesting that it is stated here that "Two thiazolium molecules, PTB (N-phenacylthiazolium bromide)^[29] and ALT-711,^[30] have demonstrated success at reducing glucosepane levels in rats"
when I've seen it asserted in other places that ALT-711 is ineffective against glucosepane crosslinks.

Clearly, any such processes are not operating well enough in older humans to keep up with damage, which thus accumulates. If the efficiency of human repair mechanisms could be maintained indefinitely at the level of a typical 11 year-old, what would be the result?

[niner]

Even glucosepane can be removed via extracellular matrix turnover according to this article: http://en.wikipedia....iki/Glucosepane

As an aside, It's interesting that it is stated here that "Two thiazolium molecules, PTB (N-phenacylthiazolium bromide)^[29] and ALT-711,^[30] have demonstrated success at reducing glucosepane levels in rats"
when I've seen it asserted in other places that ALT-711 is ineffective against glucosepane crosslinks.

Clearly, any such processes are not operating well enough in older humans to keep up with damage, which thus accumulates. If the efficiency of human repair mechanisms could be maintained indefinitely at the level of a typical 11 year-old, what would be the result?

Glucosepane could be removed, if you could get sufficient turnover, but existing turnover isn't fast enough. That assertion about PTB and ALT-711 breaking glucosepane isn't right. That's the whole problem with those compounds. I think if our repair mechanisms were maintained at the level of an eleven year-old, we would still get old. The damage just takes a long time to accrue. We need them to be better than that. I don't know of any evidence that younger people clear crosslinks faster than older people, although they probably have faster ECM turnover because it is so lightly crosslinked and possibly because they are growing.

[free10]

Let me jump in with a couple of thoughts on this thread and make a few points. In the late 90s they injected 3 different types of cell from an old man (Hayflick), with a second telomerase gene, and all got longer telomeres and looked even under a microscope to be from a newborn and kept dividing. Around 2010 we have telomerase introduced for one month, into telomerase knockout mice close to death about the 5th or 6 months and all reversed their signs of advanced aging, including the brain and organs and activities, and went on to live a normal lifespan.

Lets say tomorrow you took a powerful telomerase inducer would you go back to look like a newborn?? The answer is no and for one reason the cells in your body for the most part would not have changed a bit and have the same length damaged telomeres. It is only on division or replacement longer less damaged telomered cells will appear. The cells in your bones may wait or take 10 years for replacement. Skin cells though just weeks.

So you won't get real young fast with more telomerase unless you are mice, but you certainly will get diseased and older and die without more telomerase. Other things also can effect telomere length to shorten or lengthen them.

One small small point. We are coming out of the darkness where science and medicine said telomeres were JUNK DNA. Ten we started hearing that the telomeres were like caps on the shoe laces to keep them for coming apart by the 90s and you still hear this. The truth is the telomeres are the actual master encoding that switches DNA on or off, in the strands of DNA in the cells, so how much of this master program do you want to lose?? Especially when added back it won't all be there.

[niner]

I wouldn't go as far as to call it a master switch. Telomeres can affect the expression of a few genes that are located near the end of the chromosome. That mouse experiment showed that artificially shortened telomeres can create a phenotype that looks very much like normal aging, but that can be reversed by telomere extension. That doesn't mean that lengthening telomeres will do the same thing to a human with normal aging. Even if all telomeres were reset to a child-like length, you'd still have crosslinks, lipofuscin, amyloids, etc.

[free10]

I wouldn't go as far as to call it a master switch. Telomeres can affect the expression of a few genes that are located near the end of the chromosome. That mouse experiment showed that artificially shortened telomeres can create a phenotype that looks very much like normal aging, but that can be reversed by telomere extension. That doesn't mean that lengthening telomeres will do the same thing to a human with normal aging. Even if all telomeres were reset to a child-like length, you'd still have crosslinks, lipofuscin, amyloids, etc.

Ok, then look at the 3 types of human cells that were given the gene change to have them creating telomerase by these guys

http://www4.utsouthw...w_research.html

Extension of life-span by introduction of telomerase into normal human cells
Science 279: 349-353 (1998)

http://www.the-scien...ng-Human-Cells/

Those came originally from about a 86 year old man..Hayflick, and normally would have divided a few more times and stopped. In the 2000 article it said they had gone past 400 doublings, and going and going and going. These cells not only did this, but they also did not age anymore. Not only this but they got younger in appearance and function. They were almost identical to brand new cells, almost. Just as the lab rats that almost grew back all the brain lost to advanced aging, or liver or.............

When we talk about all the diseases and conditions, such as glycation we are talking about the world of damaged cells that are failing to operate properly. I am saying this will disappear in a world of properly functioning young cells.

Lets take a look at a more recent Harvard mice story that has little to do with telomerase or telomeres. In it they gave a single protein to old mice GDF-11. It is normally in young mice in larger amounts and becomes less and less as they grow older, and when added back into old mice their hearts with thickened heart walls like old humans the hearts were reduced in size and thickness, resembling the healthy hearts of younger mice in 30 days. Hey, that's like the same time period telomerase was reactivated the old knockout mice and made them young.

http://news.harvard....hearts-younger/

OK where am I going with this?? If the cells become young from the re lengthened telomeres, then I will bet funny little things like the increase of things, such as GDF-11 will happen a lot again ordering up repair after repair. Crosslinked proteins interfering with their function, but we can't have that, so whammo repair kicks in and new non crosslinked and fully functioning proteins take their place.

Remember too telomerase is more than a telomere builder but also a DNA fixer though it can't fix it all. Here is another little recently discovered tidbit. Cancer carefully monitors and controls its telomere length and it doesn't just mean to make sure they don't get to short and die, but also so they don't get too long. Because, if they get longer the cancerous gene coding switches back to normal, just like before the coding changes from short telomeres.

Edited by free10, 09 August 2013 - 04:46 AM.

[hav]

Remember too telomerase is more than a telomere builder but also a DNA fixer though it can't fix it all. Here is another little recently discovered tidbit. Cancer carefully monitors and controls its telomere length and it doesn't just mean to make sure they don't get to short and die, but also so they don't get too long. Because, if they get longer the cancerous gene coding switches back to normal, just like before the coding changes from short telomeres.

Do you have a cite on that?

Howard

[hav]

Here, btw, is a fairly comprehensive review of telomere length and telomerase related proteins that is current as of Feb 2012:

Maintaining the End: Roles of Telomere Proteins in End-Protection, Telomere Replication and Length Regulation

Although it mentions it in passing, It doesn't go into much detail, however, on non-telomerase based telomere length regulation via ALT. But I've only seen these mechanisms discussed in a negative light in relation to cancer.

Howard

Edited by hav, 09 August 2013 - 06:40 PM.

[HighDesertWizard]

This 54 mnute video provides an overview of a few dozen studies about the importance of Telomere Length to Aging and Disease. It highlights more anecdotal evidence that Telomerase does improve the state of Short Telomeres. (It lessens the percent of Short Telomeres.)

Edited by wccaguy, 14 August 2014 - 12:36 PM.