48 replies to this topic

[Rocket]

http://www.ibtimes.c...s-study-1484948

[nowayout]

Interesting and promising result, but I would just like to point out that this in vitro study didn't show anything close to "reverse[d] aging in human skin."  Not by a long shot. 

 

[Rocket]

Interesting and promising result, but I would just like to point out that this in vitro study didn't show anything close to "reverse[d] aging in human skin."  Not by a long shot. 

 

I would respectfully disagree that it "didn't show anything close to "reverse[d] aging in human skin."

 

"Treated cells behave as if they are much younger than untreated cells, multiplying with abandon in the laboratory dish rather than stagnating or dying." 

 

“Now we have found a way to lengthen human telomeres by as much as 1,000 nucleotides, turning back the internal clock in these cells by the equivalent of many years of human life".  If I read correctly three treatments added 10% of the original length of the telomere.

 

So they found a way to add huge % gains to the telomere length (a hallmark of aging) and it's not anything close to showing anything close to reversing aging.  Cells are prevented from becoming senescent and quiescent and it's not anything close to reversing aging?

 

I'm not a biochemist but this sounds like a huge discovery.  I wish they would hurry up and do in vivo tests on aging mice.

[nowayout]

 

Interesting and promising result, but I would just like to point out that this in vitro study didn't show anything close to "reverse[d] aging in human skin."  Not by a long shot. 

 

I would respectfully disagree that it "didn't show anything close to "reverse[d] aging in human skin."

 

"Treated cells behave as if they are much younger than untreated cells, multiplying with abandon in the laboratory dish rather than stagnating or dying." 

 

“Now we have found a way to lengthen human telomeres by as much as 1,000 nucleotides, turning back the internal clock in these cells by the equivalent of many years of human life".  If I read correctly three treatments added 10% of the original length of the telomere.

 

So they found a way to add huge % gains to the telomere length (a hallmark of aging) and it's not anything close to showing anything close to reversing aging.  Cells are prevented from becoming senescent and quiescent and it's not anything close to reversing aging?

 

I'm not a biochemist but this sounds like a huge discovery.  I wish they would hurry up and do in vivo tests on aging mice.

 

 

While telomere loss (Hayflick limit) kills cultured cells after a large number of divisions (larger than normally occurs in most human tissues during a lifespan), it is now thought that telomere loss is not a principal cause of aging or senescence in living organisms.  The Hayflick limit is not generally the bottleneck in live aging organisms, since the organism generally ages and dies long before the Hayflick limit is reached in most stem cells.   
 

Edited by nowayout, 26 January 2015 - 02:23 PM.

[Danail Bulgaria]

I have one (stupid) question to people, who understand from telomeres: If we plant skin cells on a petri dish, and we periodically lenghten their telomeres, will the skin cells divide as long as we need?

[niner]

 

 

Interesting and promising result, but I would just like to point out that this in vitro study didn't show anything close to "reverse[d] aging in human skin."  Not by a long shot. 

 

I would respectfully disagree that it "didn't show anything close to "reverse[d] aging in human skin."

 

"Treated cells behave as if they are much younger than untreated cells, multiplying with abandon in the laboratory dish rather than stagnating or dying." 

 

“Now we have found a way to lengthen human telomeres by as much as 1,000 nucleotides, turning back the internal clock in these cells by the equivalent of many years of human life".  If I read correctly three treatments added 10% of the original length of the telomere.

 

So they found a way to add huge % gains to the telomere length (a hallmark of aging) and it's not anything close to showing anything close to reversing aging.  Cells are prevented from becoming senescent and quiescent and it's not anything close to reversing aging?

 

I'm not a biochemist but this sounds like a huge discovery.  I wish they would hurry up and do in vivo tests on aging mice.

 

While telomere loss (Hayflick limit) kills cultured cells after a large number of divisions (larger than normally occurs in most human tissues during a lifespan), it is now thought that telomere loss is not a principal cause of aging or senescence in living organisms.  The Hayflick limit is not generally the bottleneck in live aging organisms, since the organism generally ages and dies long before the Hayflick limit is reached in most stem cells.  

 

Not only that, but cells are only part of the story in aging skin, and not all that big of a part.  The main difference between young skin and old skin is that the extracellular matrix in the dermis is damaged in aged skin.  All the telomeres in the world won't fix that.
 

[Rocket]

 

 

 

Interesting and promising result, but I would just like to point out that this in vitro study didn't show anything close to "reverse[d] aging in human skin."  Not by a long shot. 

 

I would respectfully disagree that it "didn't show anything close to "reverse[d] aging in human skin."

 

"Treated cells behave as if they are much younger than untreated cells, multiplying with abandon in the laboratory dish rather than stagnating or dying." 

 

“Now we have found a way to lengthen human telomeres by as much as 1,000 nucleotides, turning back the internal clock in these cells by the equivalent of many years of human life".  If I read correctly three treatments added 10% of the original length of the telomere.

 

So they found a way to add huge % gains to the telomere length (a hallmark of aging) and it's not anything close to showing anything close to reversing aging.  Cells are prevented from becoming senescent and quiescent and it's not anything close to reversing aging?

 

I'm not a biochemist but this sounds like a huge discovery.  I wish they would hurry up and do in vivo tests on aging mice.

 

While telomere loss (Hayflick limit) kills cultured cells after a large number of divisions (larger than normally occurs in most human tissues during a lifespan), it is now thought that telomere loss is not a principal cause of aging or senescence in living organisms.  The Hayflick limit is not generally the bottleneck in live aging organisms, since the organism generally ages and dies long before the Hayflick limit is reached in most stem cells.  

 

Not only that, but cells are only part of the story in aging skin, and not all that big of a part.  The main difference between young skin and old skin is that the extracellular matrix in the dermis is damaged in aged skin.  All the telomeres in the world won't fix that.
 

 

 

What creates the extracelluar matrix?  Cells. Yeah, yeah, turnover rate of collagen.... but no one can tell me for a fact really old people are wrinkled prunes because of old collagen and that their skin is thinner because of old collagen, and lacks subcutaneous fat because of old collagen.  No old people don't look as they do solely because of old collagen, but because of the cells of the body are functioning as they did when young.  Collagen turnover is just a part of it and no one can quantify its affects on appearance.

 

What prevents "old" skin from healing as well as young skin?  Cells. Certainly not the collagen in the ECM.

 

And they're not just talking skin cells, but also muscle cells as well. 

 

Also, what might this therapy do for health of blood vessels, veins, and arteries? If the old cells of those structures can be "refueled" with telomeres to behave as young cells again.... And that's what the article(s) say, that the old cells were made to act as young cells, and the senescence was positively affected.

 

Yes the telomeres of those who die of old age are not entirely depleted to ZERO, but telomeres do not have to be depleted to zero for detrimental effects on cellular health...

[CaptainFuture]

 

 

 

 

 

While telomere loss (Hayflick limit) kills cultured cells after a large number of divisions (larger than normally occurs in most human tissues during a lifespan), it is now thought that telomere loss is not a principal cause of aging or senescence in living organisms.  The Hayflick limit is not generally the bottleneck in live aging organisms, since the organism generally ages and dies long before the Hayflick limit is reached in most stem cells.   
 

 

 

I always thought, that the Hayflick limit kicks in at about 70-90 divisions? We always hear that cells are constantly dividing so isn't this a small number or do I miss something?

[nowayout]

 

 

 

 

 

 

While telomere loss (Hayflick limit) kills cultured cells after a large number of divisions (larger than normally occurs in most human tissues during a lifespan), it is now thought that telomere loss is not a principal cause of aging or senescence in living organisms.  The Hayflick limit is not generally the bottleneck in live aging organisms, since the organism generally ages and dies long before the Hayflick limit is reached in most stem cells.   
 

 

 

I always thought, that the Hayflick limit kicks in at about 70-90 divisions? We always hear that cells are constantly dividing so isn't this a small number or do I miss something?

 

 

No, it's not a small number.  It is quite likely that people tend to age and die before we get close enough to that limit to make a serious difference.  A number of other mechanisms besides telomeres are known to contribute to senescence and are probably more relevant during human lifespans.  

 

See Michael's message in this thread http://www.longecity...it/#entry274311for more information.  Unfortunately the links he references are proprietary. 

 

But to see very roughly that 70-90 divisions is not small, consider that starting with a single cell, you need 45 divisions to get the roughly 36 trillion cells making up the adult body (2^45 = 36 trillion).  Another five divisions of each cell will generate enough cells to replace the entire body 2^5 = 32 times.  Since the average cell in the adult body is estimated to last about 10 years, this admittedly naive argument indicates that only 50 divisions in total will keep you in enough cells for about 320 years after adulthood is reached.   70 divisions in total will keep you in cells for 335,544,320 years.  This is a simplification, though. Keep in mind that many somatic cells are replaced via replication of stem cells, whcih presumably divide more often but for which the Hayflick limit is also thought to be generally higher than for somatic cells.  Some tissues are replaced faster and some are not replaced, but you get the basic idea, namely that 70-90 is not a small number of divisions.

 

Also keep in mind that much of the problem with aging occurs in organs whose cells are not replaced with aging or replaced much slower than every 10 years.  This is the case with the brain and the heart, the two organs whose degeneration probably contributes most to human mortality.  We basically keep the majority of our brain and heart cells throughout adulthood, so the Hayflick limit cannot play much of a role in brain and heart senesence.
 

Edited by nowayout, 26 January 2015 - 10:28 PM.

[Antonio2014]

I always thought, that the Hayflick limit kicks in at about 70-90 divisions? We always hear that cells are constantly dividing so isn't this a small number or do I miss something?

 

Short answer:

 

Stem cells aren't affected by the Hayflick limit, because they can lenghten their telomeres. So stem cells can continuously produce new non-stem cells affected by the Hayflick limit.

 

Edit: nowayout explained it better than me.

Edited by Antonio2014, 27 January 2015 - 08:36 AM.

[Rocket]

I don't understand the dismissal of these researchers findings. A lot of people here say that aging will be tackled one item at a time, and here comes some scientists that "reverse age" skin by making the cells extend their telomeres and the attitude is kind of like "pfft, so what it doesn't do anything for the non-dividing cells."    I mean BLEEP it, if I could keep my skin and muscles youthful and worry about the organs later with later advances then sign me up!  So yeah, keep taking your astragalus and epitalon and dismiss real science.

 

[niner]

I don't understand the dismissal of these researchers findings. A lot of people here say that aging will be tackled one item at a time, and here comes some scientists that "reverse age" skin by making the cells extend their telomeres and the attitude is kind of like "pfft, so what it doesn't do anything for the non-dividing cells."    I mean BLEEP it, if I could keep my skin and muscles youthful and worry about the organs later with later advances then sign me up!  So yeah, keep taking your astragalus and epitalon and dismiss real science.

 
That would be great if you could use it to keep skin and muscles youthful in a live organism, but it's a cell culture technique.  You'd have to figure out how to do it in a person, and that's not going to be easy.  Here's the abstract of the work from pubmed:
 

FASEB J. 2015 May;29(5):1930-9. doi: 10.1096/fj.14-259531. Epub 2015 Jan 22.
Transient delivery of modified mRNA encoding TERT rapidly extends telomeres in human cells.
Ramunas J, Yakubov E, Brady JJ, Corbel SY, Holbrook C, Brandt M, Stein J, Santiago JG, Cooke JP, Blau HM.

Telomere extension has been proposed as a means to improve cell culture and tissue engineering and to treat disease. However, telomere extension by nonviral, nonintegrating methods remains inefficient. Here we report that delivery of modified mRNA encoding TERT to human fibroblasts and myoblasts increases telomerase activity transiently (24-48 h) and rapidly extends telomeres, after which telomeres resume shortening. Three successive transfections over a 4 d period extended telomeres up to 0.9 kb in a cell type-specific manner in fibroblasts and myoblasts and conferred an additional 28 ± 1.5 and 3.4 ± 0.4 population doublings (PDs), respectively. Proliferative capacity increased in a dose-dependent manner. The second and third transfections had less effect on proliferative capacity than the first, revealing a refractory period. However, the refractory period was transient as a later fourth transfection increased fibroblast proliferative capacity by an additional 15.2 ± 1.1 PDs, similar to the first transfection. Overall, these treatments led to an increase in absolute cell number of more than 10(12)-fold. Notably, unlike immortalized cells, all treated cell populations eventually stopped increasing in number and expressed senescence markers to the same extent as untreated cells. This rapid method of extending telomeres and increasing cell proliferative capacity without risk of insertional mutagenesis should have broad utility in disease modeling, drug screening, and regenerative medicine.

PMID: 25614443 PMCID: PMC4415018 [Available on 2016-05-01]

All they've really shown here is that the cells will divide longer in a dish.  They haven't shown anything about skin health.  I'm not trying to pooh-pooh their work, but the media report of it made it sound like a lot more than it is, as they usually do.  The methodology is cool, and looks like it could be very useful in cell culture for a variety of applications, but I don't see it working in vivo, at least not soon.

[Tom Andre F. (ex shinobi)]

To fight skin aging in vivo you need to fight the 3 mains causes: hyaluronidase, elastase, collagenase

[xEva]

While telomere loss (Hayflick limit) kills cultured cells after a large number of divisions (larger than normally occurs in most human tissues during a lifespan), it is now thought that telomere loss is not a principal cause of aging or senescence in living organisms.  The Hayflick limit is not generally the bottleneck in live aging organisms, since the organism generally ages and dies long before the Hayflick limit is reached in most stem cells.

 
I always thought, that the Hayflick limit kicks in at about 70-90 divisions? We always hear that cells are constantly dividing so isn't this a small number or do I miss something?

 
No, it's not a small number.  It is quite likely that people tend to age and die before we get close enough to that limit to make a serious difference.  A number of other mechanisms besides telomeres are known to contribute to senescence and are probably more relevant during human lifespans.  
 
See Michael's message in this thread http://www.longecity...it/#entry274311for more information.  Unfortunately the links he references are proprietary. 
 
But to see very roughly that 70-90 divisions is not small, consider that starting with a single cell, you need 45 divisions to get the roughly 36 trillion cells making up the adult body (2^45 = 36 trillion).  Another five divisions of each cell will generate enough cells to replace the entire body 2^5 = 32 times.  Since the average cell in the adult body is estimated to last about 10 years, this admittedly naive argument indicates that only 50 divisions in total will keep you in enough cells for about 320 years after adulthood is reached.   70 divisions in total will keep you in cells for 335,544,320 years.  This is a simplification, though. Keep in mind that many somatic cells are replaced via replication of stem cells, whcih presumably divide more often but for which the Hayflick limit is also thought to be generally higher than for somatic cells.  Some tissues are replaced faster and some are not replaced, but you get the basic idea, namely that 70-90 is not a small number of divisions.
 
Also keep in mind that much of the problem with aging occurs in organs whose cells are not replaced with aging or replaced much slower than every 10 years.  This is the case with the brain and the heart, the two organs whose degeneration probably contributes most to human mortality.  We basically keep the majority of our brain and heart cells throughout adulthood, so the Hayflick limit cannot play much of a role in brain and heart senesence.

This seems to ignore the highly variable turnover rates of various tissues. The two well-known examples from the either end of the spectrum are intestinal epithelium and neurons, with the other stuff fitting in between.

Hayflick limit and telomerase expression are important for the tissues with high turnover rates and, interestingly, that's what tends to noticeably age first, like the skin. And yes, with our current lifespans neither Hayflick no levels of telomerase are relevant for neurons and whatever is close to them in turnover rate. To disregard these differences is.. ..strange to say the least. Why, so many 'well-aging' seniors say that mentally they feel young, it's their bodies that no longer keep up with their brains (hey, not everybody gets demented with Alzheimer's or Parkinson's)

Please note that this underlines the importance of healthy telomeres (which do not have to be completely depleted for a cell to enter senescence, and all the gory consequences that come with it). True, years ago there were doubts about this, but now it's pretty clear that whatever extends telomeres extends life.

Edited by xEva, 17 November 2015 - 03:44 AM.

[corb]

To fight skin aging in vivo you need to fight the 3 mains causes: hyaluronidase, elastase, collagenase

 

This really isn't about fighting skin aging as it is about fighting skin cell aging.

They didn't investigate anything about the extracellular matrix, just epithelial cells.

[nowayout]

 

True, years ago there were doubts about this, but now it's pretty clear that whatever extends telomeres extends life.

 

 

 

Do you know any good recent citations on this?  My understanding of this issue is opposite to yours.  I know this claim was popular about 15 years ago but as far as I remember later research then deflated the telomere bubble.  As far as I remember existing animal models of telomere manipulation had disappointingly negative results, but admittedly I haven't been following the issue for the last couple of years. 

 

I know there have been recent studies that were taken by the lay press (and possibly sold as such by the researchers themselves) to show that more youthful people had longer telomeres, but they basically defined "youthful" as having longer telomeres, so it was circular. 

Edited by nowayout, 18 November 2015 - 08:23 PM.

[xEva]

True, years ago there were doubts about this, but now it's pretty clear that whatever extends telomeres extends life.

 
 
Do you know any good recent citations on this?  My understanding of this issue is opposite to yours.  I know this claim was popular about 15 years ago but as far as I remember later research then deflated the telomere bubble.  As far as I remember existing animal models of telomere manipulation had disappointingly negative results, but admittedly I haven't been following the issue for the last couple of years. 
 
I know there have been recent studies that were taken by the lay press (and possibly sold as such by the researchers themselves) to show that more youthful people had longer telomeres, but they basically defined "youthful" as having longer telomeres, so it was circular.

Last thing first, re "youthful":

I already had an experience arguing with someone here whether youth can be assessed by mere sight. So, if you're a super-scientific type who needs an array of tests to determine approximate age of a person, then sorry, I don't want step on it again. Otherwise, it's a fact that young people have longer telomeres, and that's already enough for me (mainly 'cause young people tend to live longer, no?)


As for the refs, I have not read on the topic recently and don't have them, but I'll tell you how I came to share this view. You may want to repeat my journey.

My first call came when I read on genetic mutations that negatively affect telomerase. Some people are born with this and they age faster and die sooner, usually of cancer. In the group of such conditions there are some where telomerase only of some tissues is affected (which soon results in shorter telomeres in those tissues). These people tend to die of cancer of the affected tissues. This had been known for quite a while, though it was new to me. It was eyeopening. It went in stark contrast with a prevalent opinion here that extending telomeres should lead to cancer. Turned out, it's the opposite.

And then I read a number of studies. One of them (on mice by Blasco -?) prompted me to notice a peculiar thing. A simple calculation that involved telomere length at birth and telomere attrition rate compared humans and mice and neatly showed that species' lifespan is largely determined by these 2 numbers -- though, to my knowledge, no one ran this simple calc on other species, mainly because the telomere attrition rate was not available for most. But that was a while ago, maybe these data are available now-?

You could do us all a favor in settling this matter. You could look for 3 parameters: telomere length at birth, telomere attrition rate and lifespan for various species. If this turns out as true as it seemed for humans and mice, it just may put an end to this on-going argument.

Edited by xEva, 18 November 2015 - 10:42 PM.

[nowayout]

 

My first call came when I read on genetic mutations that negatively affect telomerase. Some people are born with this and they age faster and die sooner, usually of cancer. In the group of such conditions there are some where telomerase only of some tissues is affected (which soon results in shorter telomeres in those tissues). These people tend to die of cancer of the affected tissues. This had been known for quite a while, though it was new to me. It was eyeopening. It went in stark contrast with a prevalent opinion here that extending telomeres should lead to cancer. Turned out, it's the opposite.

And then I read a number of studies. One of them (on mice by Blasco -?) prompted me to notice a peculiar thing. A simple calculation that involved telomere length at birth and telomere attrition rate compared humans and mice and neatly showed that species' lifespan is largely determined by these 2 numbers -- though, to my knowledge, no one ran this simple calc on other species, mainly because the telomere attrition rate was not available for most. But that was a while ago, maybe these data are available now-?

You could do us all a favor in settling this matter. You could look for 3 parameters: telomere length at birth, telomere attrition rate and lifespan for various species. If this turns out as true as it seemed for humans and mice, it just may put an end to this on-going argument.

 

 

A couple of points:

 

Cancer is an important problem, but it is probably separate from the problem of aging.  Most "natural" deaths of old age are not from cancer.  

 

Correlations between telomere attrition rate and lifespans are suggestive but can never prove causation.  For example, collagen attrition in human skin is highly correlated with aging, but collagen attrition in skin doesn't cause aging.  For all we know, some other underlying entropic processes may cause both aging and cause telomere attrition.

 

I suppose we will know the answer only when they make a telomere-preserving transgenic mouse that lives longer (or doesn't, as the case may be).  If or when that happens, it will be big news.  From skimming the literature, there appears to be both interventional and transgenic mouse studies where median lifespan was increased by reducing telomere attrition, which is nice; however, nobody seems to have been able to extend maximum lifespan this way, which is somewhat of a bummer for the telomere theory of aging.

 

 

 

Edited by nowayout, 24 November 2015 - 05:23 PM.

[niner]

My first call came when I read on genetic mutations that negatively affect telomerase. Some people are born with this and they age faster and die sooner, usually of cancer. In the group of such conditions there are some where telomerase only of some tissues is affected (which soon results in shorter telomeres in those tissues). These people tend to die of cancer of the affected tissues.

 

This shows us that excessively short telomeres are bad, but it doesn't mean that extra-long telomeres provide an advantage over the normal length.  This is consistent with what's been observed in telomere extension using pharmacologic means, e.g. cycloastragenol.  Improvements seen there were attributed mainly to a reduction in critically sort telomeres.

[xEva]

Correlations between telomere attrition rate and lifespans are suggestive but can never prove causation. For example, collagen attrition in human skin is highly correlated with aging, but collagen attrition in skin doesn't cause aging.  For all we know, some other underlying entropic processes may cause both aging and cause telomere attrition.

 
Collagen attrition? must be a typo and you meant depletion. I don't think those are comparable things. Collagen is a product of cells, while telomeres is an essential part of their DNA. When they become short, this results in a DNA damage signal, which effectively causes a cell to close shop. This will affect whatever that cell is producing, be it a hormone or collagen or any other protein.
 
 

This shows us that excessively short telomeres are bad, but it doesn't mean that extra-long telomeres provide an advantage over the normal length.  This is consistent with what's been observed in telomere extension using pharmacologic means, e.g. cycloastragenol.  Improvements seen there were attributed mainly to a reduction in critically sort telomeres.

 

No one speaks of extra-long telomeres here. And yes, everyone agrees that critically short telomeres are bad. It stands to reason that a therapy that lengthens telomeres will counteract their attrition and thus prolong healthy functioning of that cell. I don't see an issue here. 

[niner]

 

This shows us that excessively short telomeres are bad, but it doesn't mean that extra-long telomeres provide an advantage over the normal length.  This is consistent with what's been observed in telomere extension using pharmacologic means, e.g. cycloastragenol.  Improvements seen there were attributed mainly to a reduction in critically sort telomeres.

 

No one speaks of extra-long telomeres here. And yes, everyone agrees that critically short telomeres are bad. It stands to reason that a therapy that lengthens telomeres will counteract their attrition and thus prolong healthy functioning of that cell. I don't see an issue here. 

 

This brings up a question, and I don't know the answer to it:  What is the magnitude of the effect of telomere shortening on the aging phenotype?  Are critically short telomeres a huge problem in late life, or are they overwhelmed by all the other things that go wrong?  My gut feeling is that in most people, telomere shortening is a minor component of aging.

[sthira]

Questioning causal involvement of telomeres in aging
Ageing Research Reviews, Volume 24, Issue null, Pages 191-196
Mirre J.P. Simons

http://linkinghub.el...568163715300155

[xEva]

First this paper suffers from a number of logical flaws, then it cherry picks its animal model refs and then goes through the meta analysis of human data only to acknowledge in the end that it all was for nothing, 'cause critically short telomeres may well be "a better predictors of aging-related mortality".

And it sort of contradicts itself toward the end:

Investments in finding ways to elongate telomeres in vivo might be better spent on investigating the factors that contribute to differences in the rate of telomere shortening or the initial variance of telomere length at birth. The latter is especially interesting, considering that it might represent variation in telomere shortening in early life, with relatively constant telomere loss thereafter. This would also explain why telomere length in early life is most predictive of life expectancy, and fits with observations that events in early life have long-lasting effects, for which telomeres might then be a marker.

It's hard to understanding the resistance to the idea in this community. You know, you could view short telomeres as 'a type of damage' -- and not deviate a bit from the party line!

[niner]

It's hard to understanding the resistance to the idea in this community. You know, you could view short telomeres as 'a type of damage' -- and not deviate a bit from the party line! 

 

It doesn't matter if you call it damage or not; that's irrelevant.   A lot of people have been acting like telomere attrition is the most important factor in aging, and some of us are just questioning that.  I'm not saying telomeres aren't important at all, I'm just wondering if they are the 4th or 5th most important thing, or the 10th most important.  

 

If short telomeres contribute to aging by creating senescent cells, would senescent cell clearance be an equally good way to fix the problem?

[xEva]

If short telomeres contribute to aging by creating senescent cells, would senescent cell clearance be an equally good way to fix the problem?

probably, provided the replicative capacity (due to critically short telomeres) has not been exhausted, because you would want those cells to be replaced, no? A senescent cell is better than no cell

[alc]

If I have a copy machine (telomeres) that can copy papers up to N-th copy, without introducing any errors in the copies (duplicated cell is equally good as original), then (almost) everything is goes well. Tissues in the body will look/act like new and chances that you get sick and have visible signs of aging are reduced.

 

 

Once the copy machine (telomeres) start having problems because it produced copies above built-in/programmed life cycle, then the copies are bad (senescent cells and other things) and they start creating problems around.

 

 

Now, one wants to replace those senescent cells, and that is a good thing if you do it BUT you have to also replace/reset the copy machine (telomeres), otherwise that copy machine will continue to produce copies with errors that are sitting around, and you still have to replace them.

 

 

So the idea is to reset telomeres in order to produce good copies and get rid of the existing senescent cells. Once you do both of these, the copy machine can work as it was new, and there are no bad copied cells around.

 

 

If you just get rid of senescent cells without resetting telomeres (=copy machine) senescent cells are keep coming and you still have to remove them. Why would you do just that?

 

 

Michael Fossel (I know couple individuals cannot stand him for reasons I do not understand) explain very well and clear these issues.

 

I do suggest reading his posts, books and comments without any bias in mind. Myself I read like that posts of most of players in this reverse aging field:

 

 

http://www.michaelfo...com/blog/?p=145

 

 

https://www.singular...or-immortality/

 

 

His point is that resetting telomeres, is one of the most effective anti-aging therapies that are available right now (as opposed to others that will take good decades to be implemented). If done well, could lead to improved health benefits.

 

Also, now there are new insights into the discussion that telomerase will induce cancer in cells, as cancer uses that backdoor to hijack. But inducing telomerase doesn't automatically result in cancer – and this is a discussion that can go on forever, until tested for real.

 

 

Read into CNIO research:

 

 

https://www.cnio.es/...?grupo=50004259

 

 

... and the newly study published by Carol Greider about ATM kinase, actually reinforce these ideas:

 

 

Beyond Telomerase: Researchers Discover Other Enzyme Critical to Maintaining Telomere Length

 

 

"Figuring out exactly what’s needed to lengthen telomeres has broad health implications,

Greider notes, because shortened telomeres have been implicated in aging and in diseases

as diverse as lung and bone marrow disorders, while overly long telomeres are linked to cancer.

Because telomeres naturally shorten each time DNA is copied in preparation for cell division,

cells need a well-tuned process to keep adding the right number of building blocks back

onto telomeres over an organism’s lifetime."

 

http://www.hopkinsme...telomere_length

 

 

 

… but AGAIN all these needs to be proved in real clinical studies … that is why I keep repeating: why certain people (here and other places) fight to death to oppose Michael Fossel and others, when they are trying to test these soon?

 

What is the hold up? I don't get it. We all should be happy to see things tested for real and we will know the result.

 

We will have a chance to see if these are working or not in humans, instead of just nice cell/mice studies and keep arguing for decades.

 

 

 

 

[niner]

 

If short telomeres contribute to aging by creating senescent cells, would senescent cell clearance be an equally good way to fix the problem?

probably, provided the replicative capacity (due to critically short telomeres) has not been exhausted, because you would want those cells to be replaced, no? A senescent cell is better than no cell

 

A senescent cell may or may not be better than no cell.  Senescent cells secrete pro-inflammatory signals that can damage surrounding tissue, so it's really good to get them out of there.  If there is a different stem cell with longer telomeres that could replace the senescent cell, that would be good.  Clearly, if all the stem cells are in an equal state of telomere depletion, then the only answer is to extend those stem cell telomeres in some fashion.  But how common is telomere depletion in stem cells, given that stem cells normally have competent telomerase?

[niner]

If you just get rid of senescent cells without resetting telomeres (=copy machine) senescent cells are keep coming and you still have to remove them. Why would you do just that?

 

See my previous post.
 

Michael Fossel (I know couple individuals cannot stand him for reasons I do not understand) explain very well and clear these issues.
 
I do suggest reading his posts, books and comments without any bias in mind. Myself I read like that posts of most of players in this reverse aging field:
 
His point is that resetting telomeres, is one of the most effective anti-aging therapies that are available right now (as opposed to others that will take good decades to be implemented). If done well, could lead to improved health benefits.

I wouldn't say that I "can't stand him", since I don't even know him, but I have some disagreements with his public statements.  He seems to be promoting telomere attrition as the most important cause of aging on the basis of rather thin evidence.  His promotion is largely to a lay public that is ill-equipped to judge the validity of his premises.  He has recently released a book, "The Telomerase Revolution", and has a startup, Telocyte, that promises to "cure Alzheimers" (despite the unclear relationship between telomere length and Alzheimer's pathology), so he has something to sell.  He places himself in the "evolved aging" camp, which I don't agree with, but a bigger problem is that he derives from that idea the unlikely notion that programmed aging is easy to fix, while aging that involved damage accumulation would be extremely difficult to fix.  In fact we are making qood progress on damage repair.  There is some work being done on the "de-programming" (sort of) front, like Liz Parrish's AAV HTERT experiment and Steve Perry's GDF11 self-experimentation, but this stuff is small scale and very far from the clinic.  There's little evidence that it will be both easy and truly effective.  My complaint about Fossel is that he seems like a "true believer" who has gotten a little ahead of the science.  I'd hate to see a poorly-supported but highly promoted effort fail and taint the field, and I would hate to see incorrect ideas get enough traction to divert resources into a dead end and ultimately slow the cure of aging.   

 

I have to question the idea that resetting of telomeres is available right now, and that it is an effective anti-aging technology.  Where is it available today?  (in an effective form)  How do we know it reverses the effects of aging?  It looks like Fossel's project with Telocyte is well over a decade away from availability, assuming it passes all the hurdles before it.    I think that we will see therapies like stem cell augmentation and senescent cell clearance before we see telomerase gene therapy.

 

No one should approach the literature with a bias, and most of us try not to.  On the other hand, we should always be critical of what we read.  We should ask what the evidence is for the claims being made, check the logic, and be on the lookout for conflicts of interest and ulterior motives on the part of the presenters. 

 

Since you said that you didn't understand people's reasons for being uncomfortable with Fossel, these are my reasons.  All of them are up for discussion, of course.  I just didn't want you to think that there were no reasons.

[sthira]

...There is some work being done on the "de-programming" (sort of) front, like Liz Parrish's AAV HTERT experiment ...

I hope this is on point; but here's more from Liz Parish:

http://youtu.be/vLkCF4m3wk8

[alc]

1. "See my previous post."

 

yes I have read that

 

"If short telomeres contribute to aging by creating senescent cells, would senescent cell clearance be an equally good way to fix the problem?"

 

That is why I was questioning why you want to just remove senescent cells, without replacing/resetting the telomeres?

 

 

 

2. "He seems to be promoting telomere attrition as the most important cause of aging on the basis of rather thin evidence."

 

Again, please read what he says, then post.

 

 

3. " ... and has a startup, Telocyte, that promises to "cure Alzheimers" (despite the unclear relationship between telomere length and Alzheimer's pathology), so he has something to sell."

 

Well, to be honest I would rather see something that cost me money and be developed, than commies ideas that "the technologies will be free for everybody", but with the pace they are developed will take eons ...

 

 

4. "In fact we are making qood progress on damage repair."

 

I'm very interested to see clear evidence that work in humans. Can you point out where to look at? I have looking/reading FA for good years, and all the time the poster there was talking about things like are around the corner. Also the guys from SENS are attacking everybody else, like they are holding the solution in their pocket ... but now a decade later ...

Don't be confused by the "fundamental"research that they are doing, and the big steps from there into humans. I have family and close friends that worked/working in clinical research programs for large univeristies and I know for sure that that actually is the biggest obstacle. Most of SENS work looks very good because is done at that level.

 

On the bright side:

 

NeuroPhage was mentioned (http://neurophage.com/)

Oisin Biotechnology - but there is not much on the web

 

So, I'm very, very interested to see results in humans. Seriously, I'm looking forward to some results.

 

But on the negative side, for what can be seen for past year or so, SENS guys are a lot into "defensive" position, trying to cast doubt on any study that doesn't rhyme with their plan. Not mean that all they do/say is wrong, but they have quite few issues, and are acting like in the story with the Emperor's clothes.

 

They have fragments that patch "here and there", but there is a looooooooong way from there.

 

I donated to MitoSENS to see where is goes. Same thing, I donated to SENS every time I could, hoping they understand what needs to be adjusted in their work. However, there is more and more ego on their work, that un-biased approach.

 

As a matter of fact I want to propose here on Longecity to start a monitoring program, where we 

keep track of any meaningful project/company (programmed, or wear and tear, etc.) and see exactly where they stand.

 

 

5.  "There is some work being done on the "de-programming" (sort of) front, like Liz Parrish's AAV HTERT experiment and Steve Perry's GDF11 self-experimentation, but this stuff is small scale and very far from the clinic.  There's little evidence that it will be both easy and truly effective.  My complaint about Fossel is that he seems like a "true believer" who has gotten a little ahead of the science.  I'd hate to see a poorly-supported but highly promoted effort fail and taint the field, and I would hate to see incorrect ideas get enough traction to divert resources into a dead end and ultimately slow the cure of aging."

 

 

Makes me  wonder if you really read things like I mentioned in my post? Do you really read and compute studies before posting? Or you just go ahead and post regardless?

Also, if you remember I posted before: now George Church is backing same approach like Michael Fossel

We will see where that goes, but I have a feeling that George Church and his team will have something to show.

 

 

6. "I have to question the idea that resetting of telomeres is available right now, and that it is an effective anti-aging technology.  Where is it available today? "

 

You just answer to yourself above, without realizing. Sorry, I know sounds not friendly at all, but you do really have issues with logical connection between things you post.

 

 

7. "How do we know it reverses the effects of aging?"

 

You cannot be serious asking this, are you? here are couple things (apologize for being sarcastic): step one, buy a mirror ... now seriously: you know that there are few things that determine the biological age?  ... please do a Google search for that ... if you do not know that there is "let me google it for you" ... lol ... please read here:

 

http://www.genomebio...m/2015/16/1/185

 

http://www.ncbi.nlm....les/PMC4015143/

 

http://www.biomedcen.../1741-7007/13/7

 

 

 

8. "It looks like Fossel's project with Telocyte is well over a decade away from availability, assuming it passes all the hurdles before it.    I think that we will see therapies like stem cell augmentation and senescent cell clearance before we see telomerase gene therapy."

 

That might be the case, I'm really happy to see ANYTHING that really works for reverse aging.

 

... as for your bias towards certain studies/approaches, I'll keep my comment ... I'm better off focusing on productive things, because there are so many missing things on your constructs, that it's just hard to explain ... yeah, really better focus on productive things, but it just bother me to see how you (like the FA guy) spread the "truth" in right and left, being so out of target ... or sould I use "off-target" ...

 

This is getting off-topic, so I'm stopping now - probably most important thing for you is to keep an eye on George Church's work/lab, as they will come up with things on above discussions:

 

http://arep.med.harvard.edu/gmc/

 

 

 

 

and oops forgot to mention: George Church and his team really love synthetic biology ... which is very close to programming, really programming ... and there are lots of large players that are looking into that:

 

http://www.eetimes.c...?doc_id=1325390

 

http://www.fool.com/...etic-biolo.aspx

 

http://www.autodeskr...projects/cyborg

 

 

good luck with your posts.

Edited by alc, 28 November 2015 - 04:18 AM.