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The top five telomere myths

telomeres

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#1 hplus

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Posted 22 April 2023 - 05:26 PM


I wrote an article about the language scientists use when talking about telomeres. In my view, the terminology no longer fits new empirical data about telomeres. The outdated language creates a lot of confusion which I call the top five telomere myths:

  1. Telomeres are protective caps at the end of chromosomes.
  2. Cellular replication causes telomere attrition.
  3. Telomere shortening cannot cause aging, as some short-lived animals, such as mice, have long telomeres.
  4. The Hayflick limit evolved as a cancer suppressor.
  5. Telomeres do not encode.

I am very much interested in feedback, positive and negative.

 


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#2 Mind

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Posted 22 April 2023 - 07:20 PM

As far as I have seen, #4 on the list is just a theory. I am unsure there is any data to back this up - just that it kind-of makes sense from an evolutionary perspective.


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#3 hplus

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Posted 23 April 2023 - 11:50 AM

Yeah, #4 is the only myth that is not based on the improper use of language. Most geroscientists take it for granted because it seems self-evident for them, and they don't feel the need to confirm this claim with empirical data. However, in my view, the fact that long-lived animals with a generous Hayflick-limit rarely get cancer has falsified this theory.


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#4 QuestforLife

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Posted 26 April 2023 - 11:31 AM

Yeah, #4 is the only myth that is not based on the improper use of language. Most geroscientists take it for granted because it seems self-evident for them, and they don't feel the need to confirm this claim with empirical data. However, in my view, the fact that long-lived animals with a generous Hayflick-limit rarely get cancer has falsified this theory.

 

And also the fact that cancer (by and large, I am not including childhood cancers here) increase exponentially with age, which matches what we know from cell culture, where genomic stability declines as telomeres shorten. 


Edited by QuestforLife, 26 April 2023 - 11:31 AM.


#5 QuestforLife

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Posted 26 April 2023 - 11:35 AM

You're wrong on 2. Cells' telomeres shorten inarguably with cell division (in the absence of sufficient telomerase to offset it), at least in vitro. 

 

You might argue in vivo that things are more complex, with some cell populations able to increase telomere length (for example leukocytes), but this is normally due to a reduction of telomere loss between the progenitor population and the leukocytes themselves due to changes in other factors like oxidative stress or the total number of leukocytes produced. Overall telomere length will still have declined (once you include stem cell populations).

 

Edit - ah, I see by looking at your article that you are taking issue with the word 'attrition'. I get it, but it is not relevant to life extension as everybody that matters knows this is not 'wear and tear'.


Edited by QuestforLife, 26 April 2023 - 11:42 AM.


#6 hplus

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Posted 26 April 2023 - 12:15 PM

QuestforLife, I studied the history and the philosophy of science, and I can tell you words matter a lot because they determine the paradigm. If scientists work in the wrong paradigm, progress is very slow; sometimes, there is no progress at all. This also applies to this case. Talking of "telomere attrition" allows researchers to stay in the old paradigm, which claims that the wear and tear of metabolism causes aging. If you use the theoretically correct term, which is telomere countdown, you automatically admit that telomeres play a crucial role in programmatically determining the lifespan of organisms. If scientists didn't work in the wrong paradigm for the last 20 years, we probably would have a cure for aging already.

 

As to cancer, I suggest you read the article. There is overwhelming evidence that the telomere countdown did not evolve to keep cancer in check.


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#7 QuestforLife

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Posted 26 April 2023 - 01:52 PM

QuestforLife, I studied the history and the philosophy of science, and I can tell you words matter a lot because they determine the paradigm. If scientists work in the wrong paradigm, progress is very slow; sometimes, there is no progress at all. This also applies to this case. Talking of "telomere attrition" allows researchers to stay in the old paradigm, which claims that the wear and tear of metabolism causes aging. If you use the theoretically correct term, which is telomere countdown, you automatically admit that telomeres play a crucial role in programmatically determining the lifespan of organisms. If scientists didn't work in the wrong paradigm for the last 20 years, we probably would have a cure for aging already.

 

As to cancer, I suggest you read the article. There is overwhelming evidence that the telomere countdown did not evolve to keep cancer in check.

 

I see you have an even lower opinion of the current crop of scientists than I do - touche.

 

As to the cancer comment, I do not understand, my comment was in support of your point. 



#8 CynthesisToday

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Posted 26 April 2023 - 03:18 PM

And also the fact that cancer (by and large, I am not including childhood cancers here) increase exponentially with age, which matches what we know from cell culture, where genomic stability declines as telomeres shorten. 

 

https://onlinelibrar....1111/eva.13514 "Modeling of senescent cell dynamics predicts a late-life decrease in cancer incidence" (2022) 

 

Cancer rates increase with age until they start to slow (after ~75yo) and primarily stop being a cause of death in centenarians.

 

The introduction of the above paper provides links (see Cook, et.al. 1965 as a start) and explanation rebuttals in support of this statement. 



#9 hplus

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Posted 26 April 2023 - 03:56 PM

I see you have an even lower opinion of the current crop of scientists than I do - touche.

 

As to the cancer comment, I do not understand, my comment was in support of your point. 

 

I don't have a low opinion of geroscientists. Cell biology is very complex, and contradicting theories are expected to emerge. The good news is that an increasing number of scientists are switching to the new paradigm. I just saw an interview with George Church, and he seems to support now the theory that aging is a programmed process.

 

The fact that the cancer risk increases with age is often put forward as proof that the telomere countdown has evolved to lower the cancer risk because the likelihood that cancerous mutations develop increases with the number of cell divisions. So the theory is that the Hayflick limit evolved to stop these cells from proliferating. However, as I explained in my article, this theory is wrong because animals with a much more generous Hayflick limit rarely develop cancer. After all, much simpler mechanisms exist to keep unruly cells in check. Thus, the only purpose of the Hayflick limit is to determine the optimal maximal lifespan of a species programmatically.



#10 hplus

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Posted 26 April 2023 - 04:06 PM

https://onlinelibrar....1111/eva.13514 "Modeling of senescent cell dynamics predicts a late-life decrease in cancer incidence" (2022) 

 

Cancer rates increase with age until they start to slow (after ~75yo) and primarily stop being a cause of death in centenarians.

 

The introduction of the above paper provides links (see Cook, et.al. 1965 as a start) and explanation rebuttals in support of this statement. 

 

This is expected because the Hayflick limit programmatically eliminates stem cells which are probably the major driver of cancer development. Centenarians usually suffer from stem cell elimination. However, stem cell elimination has not evolved to reduce the cancer risk. Its only purpose is to kill the organism once the maximum lifespan has been reached.



#11 QuestforLife

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Posted 27 April 2023 - 08:28 AM

https://onlinelibrar....1111/eva.13514 "Modeling of senescent cell dynamics predicts a late-life decrease in cancer incidence" (2022) 

 

Cancer rates increase with age until they start to slow (after ~75yo) and primarily stop being a cause of death in centenarians.

 

The introduction of the above paper provides links (see Cook, et.al. 1965 as a start) and explanation rebuttals in support of this statement. 

 

This isn't actually a contradiction - as decreased proliferative capacity impedes cancer development. So as telomeres shorten you get an increase in cancer rates followed by a decrease. Obviously this wouldn't apply to animals with very long telomeres like mice, but it does apply to humans. 


Edited by QuestforLife, 27 April 2023 - 08:51 AM.


#12 QuestforLife

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Posted 27 April 2023 - 08:49 AM

As to cancer, I suggest you read the article. There is overwhelming evidence that the telomere countdown did not evolve to keep cancer in check.

 

I've been reading and studying papers on aging with a particular interest in telomeres for over ten years, with much of this recorded on my thread

I am well aware of the arguments. 

I am probably the strongest proponent of telomeres being the kingpin of aging in humans on this site.  But I think the truth is more nuanced than either 'it evolved to control cancer' or 'it evolved to set lifespan'. 

 

Thus, the only purpose of the Hayflick limit is to determine the optimal maximal lifespan of a species programmatically.

 

I don't think telomeres evolved with a single purpose across all species.

Evolution is very haphazard. Look at the extreme length of telomeres in some mice species. A length that they have absolutely no use for. Most likely they need telomerase to protect them from oxidative stress in mitochondria and a side effect is long telomeres. Therefore, length of their telomeres is not relevant in mouse lifespan. 

 On the other hand humans have very short telomeres, which most likely does limit our maximum lifespan.



#13 hplus

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Posted 27 April 2023 - 10:02 AM

I've been reading and studying papers on aging with a particular interest in telomeres for over ten years, with much of this recorded on my thread

I am well aware of the arguments. 

I am probably the strongest proponent of telomeres being the kingpin of aging in humans on this site.  But I think the truth is more nuanced than either 'it evolved to control cancer' or 'it evolved to set lifespan'. 

 

 

I don't think telomeres evolved with a single purpose across all species.

Evolution is very haphazard. Look at the extreme length of telomeres in some mice species. A length that they have absolutely no use for. Most likely they need telomerase to protect them from oxidative stress in mitochondria and a side effect is long telomeres. Therefore, length of their telomeres is not relevant to mouse lifespan. 

 On the other hand, humans have very short telomeres, which most likely does limit our maximum lifespan.

 

Mice have a much higher cancer higher risk than humans. They have long telomeres, and their somatic cells even express telomerase. However, their telomere countdown timer ticks 100 times faster than in humans. Thus, their Hayflick limit is only 15–20 cycles, which is why their maximum lifespan is very short. The Hayflick limit of humans is 40–60 cycles.

 

Mice with a small Hayflick limit have a high cancer risk. This alone falsifies the theory that the Hayflick limit evolved to reduce cancer risk. You can find similar contradictions with other species where the Hayflick limit is known.

 

Please read my article for references. 

 

As far as I know, telomeres have the same function in all species. Even in yeast, the primary purpose is to cause aging and limit the lifespan.

 

I find it fascinating that many scientists are unaware of or ignore much of the empirical evidence about telomeres. Unfortunately, there are many comparable examples in the history of science. It always takes a long time until an old paradigm is replaced with a new one despite mounting evidence against the old paradigm. Many bioscientists are surprisingly conservative and have a hard time giving up their grad school knowledge.



#14 QuestforLife

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Posted 27 April 2023 - 11:43 AM

Mice have a much higher cancer higher risk than humans. They have long telomeres, and their somatic cells even express telomerase. However, their telomere countdown timer ticks 100 times faster than in humans. Thus, their Hayflick limit is only 15–20 cycles, which is why their maximum lifespan is very short. The Hayflick limit of humans is 40–60 cycles.

 

Mice with a small Hayflick limit have a high cancer risk. This alone falsifies the theory that the Hayflick limit evolved to reduce cancer risk. You can find similar contradictions with other species where the Hayflick limit is known.

 

Please read my article for references. 

 

As far as I know, telomeres have the same function in all species. Even in yeast, the primary purpose is to cause aging and limit the lifespan.

 

I find it fascinating that many scientists are unaware of or ignore much of the empirical evidence about telomeres. Unfortunately, there are many comparable examples in the history of science. It always takes a long time until an old paradigm is replaced with a new one despite mounting evidence against the old paradigm. Many bioscientists are surprisingly conservative and have a hard time giving up their grad school knowledge.

 

It is very refreshing for me to discuss this with someone who is an even more aggressive advocate for telomeres being causal in aging than I am. Please come and join the forum!

 

As for your point about mice having a lower Hayflick limit than humans, this not quite right. 

 

It is true that murine cells senescence in culture much more quickly than human ones do. But this is due to oxidative stress rather than telomere shortening due to the number of past replications (of course the two are not completely independent). Please see this excellent paper for a full explanation [1].

 

Further, we can see the effect of telomere length in mice in a brilliant experiment [2] when they bred mice with only one active copy of the mTERT gene in order to create a range of offspring. What they found was that mice inheriting two duff mTERT copies lost telomere length between generations, becoming unable to breed after multiple generations, as been reported elsewhere. Mice inheriting one good and one bad copy also experienced an inter generational telomere loss, but at a much slower rate. But what was most interesting is that when at various generational points, mice were lucky enough to get two good copies of the mTERT gene, they didn't elongate telomeres back to what their original forebears had, they just maintained it at the inherited length throughout all future generations (See Fig2 C). This speaks to my earlier point of telomere length being arbitrary in many small species.

 

In experiments with telomerase-deficient mice losing telomere lengths between generations, of which there is a wealth of literature,  you'd expect a declining lifespan, but it doesn't happen, not until the telomeres get very short after many generations. This shows that it is not the hayflick limit that is limiting mice lifespan (though as I stated previously, it probably does limit human lifespan, as it does very late generation telomerase-deficient mice).

 

 

[1] Parrinello S, Samper E, Krtolica A, Goldstein J, Melov S, Campisi J. Oxygen sensitivity severely limits the replicative lifespan of murine fibroblasts. Nat Cell Biol. 2003 Aug;5(8):741-7. doi: 10.1038/ncb1024. Erratum in: Nat Cell Biol. 2003 Sep;5(9):839. PMID: 12855956; PMCID: PMC4940195.

 

[2] Chiang YJ, Calado RT, Hathcock KS, Lansdorp PM, Young NS, Hodes RJ. Telomere length is inherited with resetting of the telomere set-point. Proc Natl Acad Sci U S A. 2010 Jun 1;107(22):10148-53. doi: 10.1073/pnas.0913125107. Epub 2010 May 17. PMID: 20479226; PMCID: PMC2890496.


Edited by QuestforLife, 27 April 2023 - 11:46 AM.


#15 hplus

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Posted 27 April 2023 - 02:43 PM

Your reference is very old. Twenty years ago, most scientists still believed in the free radical theory of aging. We now know that the situation in vivo is totally different because multicellular organisms can easily deal with ROS.

 

What we do know is that under the same conditions, human cells divide 40-60 times, and murine cells only 15-20 times. We also know that the telomeres of mouse cells shorten 100 times faster than in human cells. I also feel it is insufficient to only measure the absolute telomere length. You also have to determine the length at which the p53 switch is triggered because this is the primary function of the telomere countdown timer. We have to expect that the mechanisms here are species-dependent. 

 

And let's not forget that mice like humans with long telomeres live longer.

 

Mice with hyper-long telomeres show less metabolic aging and longer lifespans


Edited by hplus, 27 April 2023 - 02:44 PM.


#16 QuestforLife

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Posted 27 April 2023 - 04:08 PM

Your reference is very old. Twenty years ago, most scientists still believed in the free radical theory of aging. We now know that the situation in vivo is totally different because multicellular organisms can easily deal with ROS.

What we do know is that under the same conditions, human cells divide 40-60 times, and murine cells only 15-20 times. We also know that the telomeres of mouse cells shorten 100 times faster than in human cells. I also feel it is insufficient to only measure the absolute telomere length. You also have to determine the length at which the p53 switch is triggered because this is the primary function of the telomere countdown timer. We have to expect that the mechanisms here are species-dependent.


What difference does it make what scientists believe? Or how old a paper is? Evidence is evidence.

Indeed murine cells do divide less times than human ones under the same conditions. But what are those conditions? Atmospheric oxygen is the answer. A condition of high oxidative stress.

I have not seen in vitro evidence that under the 'same condtions' mouse cells' telomeres shorten 100x faster than human ones. Senesce yes. But not due to replicative arrest. Have you got that evidence?

Blasco has some data showing species specific telomere shortening rate predicts max lifespan. But that's in vivo so it's hard to say for sure it's causal. Also, there's been no replication of the paper.

I think she may be right, and I also like her other work, including the paper on hyperlong telomeres you link to. But again, it is hard to decouple telomere lifespan effects from the fact those mice were just healthier overall. Something remains to be explained.


And let's not forget that mice like humans with long telomeres live longer.

Mice with hyper-long telomeres show less metabolic aging and longer lifespans


Do you have any response on my other reference [2] re: the arbitrary length of telomeres in lab mice?

#17 hplus

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Posted 27 April 2023 - 04:35 PM

Want to experience oxidative stress? Stop breathing for a couple of minutes.

 

Yes, oxygen is a highly reactive chemical. However, this is precisely why it is so valuable. Aerobic organisms have evolved to deal with oxygen. These old studies created artificial conditions where the natural defense mechanisms against ROS don't come into play. The reason why supplementation with antioxidants decreases lifespan is that these natural defense mechanisms are then downregulated. The free radical theory of aging died long ago because of radical new theories of aging.

 

Read the Nature article I linked to. It mentions that mice telomeres shorten 100 times faster than in humans.

 

I don't know what you mean by "arbitrary length of telomeres in lab mice."



#18 QuestforLife

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Posted 27 April 2023 - 09:09 PM

The Blasco paper that samples leukocytes from mice of different ages and shows they shorten at approx 7000 bases/year is this one [1].

Still doesn't answer the question though on whether mice cells senesce more quickly than humans because of oxidative stress or the end replication problem.

If you look at my second reference 4 posts up you'll see what I'm talking about regarding the arbitrary length of telomeres in lab mice. The point is they can vary greatly without having much impact. This is not to say telomere length in humans is not important or that the rate of shortening is not important across species. Just to point out mice have lots of telomeres to spare.

Here is another paper that speaks to that point [2]. Here they show a huge variation in telomere length between mice species with no correlation between telomere length and lifespan. In fact the species with the longest lifespan had the shortest telomeres. Now perhaps that is because their short telomeres shortened at the slowest rate. But here we are going round in circles, as we don't know if that is due to lower production of ROS from mitochondria, better efficiency of the telomerase protein, or whatever.

[1] Vera E, Bernardes de Jesus B, Foronda M, Flores JM, Blasco MA. The rate of increase of short telomeres predicts longevity in mammals. Cell Rep. 2012 Oct 25;2(4):732-7. doi: 10.1016/j.celrep.2012.08.023. Epub 2012 Sep 27. PMID: 23022483.

[2] Hemann MT, Greider CW. Wild-derived inbred mouse strains have short telomeres. Nucleic Acids Res. 2000 Nov 15;28(22):4474-8. doi: 10.1093/nar/28.22.4474. PMID: 11071935; PMCID: PMC113886.

#19 CynthesisToday

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Posted 27 April 2023 - 11:17 PM

Who is the intended audience for the "5 myths..." article?

 

Within the first few paragraphs you say "...language of cell biologists..." and "...published papers..." and then quote a popular media source (Wikipedia) for the source of the language instead of the introduction portions of the peer reviewed publications from the cell biologists your article is lecturing/berating/admonishing. 

 

In the Myth #2 section this method is repeated with the use of a quote from Elizabeth Blackburn's popular science book you link from the Amazon.com website section "Health, Fitness & Dieting", the cherry-picked 4th definition from Dictionary.com ("wearing away or down by friction") instead of the 1st definition ("a reduction or decrease in number, size or strength") and then say "What I find fascinating here is that a scientist who received a Nobel Prize for her research about telomeres doesn’t bother to explain in her book about the very same topic what is actually happening here. I mean, this is the one and only thing that is really fascinating about telomeres, and this discovery would have been really worthy of a Nobel Prize."

 

(My internal monologue is saying "Gee, the Nobel Committee should have asked you". My internal monologue is also wondering what purpose telomeres serve in reproduction and development-- strong drivers of evolution.)

 

This is followed by: "I can’t go into the details in this blog post, but attrition is certainly not the reason telomeres shorten." I can agree that wear and tear as if by friction is not the reason telomeres shorten but the best and most common definition of attrition is not the one you chose. It's also not the one I read about in the original, peer-reviewed publications I read. I see the terms "telomere attrition" and "telomere length" (TL) most often (by far). It is clear within the context of the introduction portion of the research articles that attrition means loss without replacement.  If you're going to contrive definitions to drive your narrative I'm not inspired to read further (although I did read to the end of your linked article). The overall tone of chastisement and belittlement of the linked article ends my interest in continuing with feedback on the ability of the rest of the article to communicate.

 

People who regularly read the published literature are probably not your intended audience. If they are, at least one of them is not inspired to continue to read what you write. I will say that reading the link in the OP did inspire me to go read more of professionally published, peer-reviewed, original research articles on telomeres and their primary function in biology (reproduction and development... the aging thing is interesting). Thanks for that inspiration. I found this really well-written, well-researched PhD Thesis by Ye Xiong (2023): https://portal.resea...opmental-effect "What Modulates Telomere Dynamics? Inheritance, Developmental Effects and Physiological Challenges". It's free and starts with a research abstract _and_ a popular science summary. No wear and tear in the there.

 

As a reminder, in the original post you say: "I am very much interested in feedback, positive and negative." I interpreted that as feedback on the article's ability to communicate not on the accuracy of the content. If you meant something else, you should have said so.


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#20 CynthesisToday

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Posted 28 April 2023 - 01:36 AM

 

 I found this really well-written, well-researched PhD Thesis by Ye Xiong (2023): https://portal.resea...opmental-effect "What Modulates Telomere Dynamics? Inheritance, Developmental Effects and Physiological Challenges". 

 

This author participated in a paper that gives a very thorough overview of the various hypotheses of telomeres in ecology and evolution.  

 

https://onlinelibrar....1111/mec.16308 "Telomeres in ecology and evolution: A review and classification of hypotheses" (2021)

 

It seems pretty clear reviewing all of the different hypotheses that telomere involvement in aging is pretty far from a settled theory. Great diagrams and timelines. Research questions asked when gathering data drive hypotheses. These include aging, marker of quality, mediator of tradeoffs and physiological currency.


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#21 hplus

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Posted 28 April 2023 - 09:05 AM

The Blasco paper that samples leukocytes from mice of different ages and shows they shorten at approx 7000 bases/year is this one [1].

Still doesn't answer the question though on whether mice cells senesce more quickly than humans because of oxidative stress or the end replication problem.

If you look at my second reference 4 posts up you'll see what I'm talking about regarding the arbitrary length of telomeres in lab mice. The point is they can vary greatly without having much impact. This is not to say telomere length in humans is not important or that the rate of shortening is not important across species. Just to point out mice have lots of telomeres to spare.

Here is another paper that speaks to that point [2]. Here they show a huge variation in telomere length between mice species with no correlation between telomere length and lifespan. In fact the species with the longest lifespan had the shortest telomeres. Now perhaps that is because their short telomeres shortened at the slowest rate. But here we are going round in circles, as we don't know if that is due to lower production of ROS from mitochondria, better efficiency of the telomerase protein, or whatever.

[1] Vera E, Bernardes de Jesus B, Foronda M, Flores JM, Blasco MA. The rate of increase of short telomeres predicts longevity in mammals. Cell Rep. 2012 Oct 25;2(4):732-7. doi: 10.1016/j.celrep.2012.08.023. Epub 2012 Sep 27. PMID: 23022483.

[2] Hemann MT, Greider CW. Wild-derived inbred mouse strains have short telomeres. Nucleic Acids Res. 2000 Nov 15;28(22):4474-8. doi: 10.1093/nar/28.22.4474. PMID: 11071935; PMCID: PMC113886.

 

Again, you are citing very old papers. I would rather go with the latest research in the Nature paper. That oxidative stress shortens telomeres at such a breathtaking speed makes no sense from a theoretical point of view. How should this work biochemically in a living organism? Oxidative stress can damage molecules but not programmatically remove telomeres at a constant speed. You have to see these old papers in the historical context. At that time, oxidative stress was the culprit for almost everything
 
Nevertheless, what is important here is that mice have a higher cancer risk even though their cells have a lower cell cycle limit. Comparison with other animals reveals that the cell cycle limit is not linked to cancer risk.


#22 QuestforLife

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Posted 28 April 2023 - 09:35 AM

 

Again, you are citing very old papers. I would rather go with the latest research in the Nature paper. That oxidative stress shortens telomeres at such a breathtaking speed makes no sense from a theoretical point of view. How should this work biochemically in a living organism? Oxidative stress can damage molecules but not programmatically remove telomeres at a constant speed. You have to see these old papers in the historical context. At that time, oxidative stress was the culprit for almost everything
 
Nevertheless, what is important here is that mice have a higher cancer risk even though their cells have a lower cell cycle limit. Comparison with other animals reveals that the cell cycle limit is not linked to cancer risk.

 

 

I agree with you that long telomeres do not cause cancer. 

 

I just think your justification, based on hayflick limit in mice, is wrong. Let's leave it at that for now.

 

I like the old papers*. But I read all papers I can get my hands on, and have already read all the papers you've mentioned, some like the ones out of Maria Blasco's lab, many times. 

 

*ps the Nature paper you referenced for the 100x faster telomere shortening rate in mice claim, referenced as proof THE PAPER I POSTED ABOVE. So don't dismiss the old. It is what the new is built on...


Edited by QuestforLife, 28 April 2023 - 09:39 AM.


#23 hplus

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Posted 28 April 2023 - 09:40 AM

 

Who is the intended audience for the "5 myths..." article?

 

Within the first few paragraphs you say "...language of cell biologists..." and "...published papers..." and then quote a popular media source (Wikipedia) for the source of the language instead of the introduction portions of the peer reviewed publications from the cell biologists your article is lecturing/berating/admonishing. 

 

(My internal monologue is saying "Gee, the Nobel Committee should have asked you". My internal monologue is also wondering what purpose telomeres serve in reproduction and development-- strong drivers of evolution.)

 

This is followed by: "I can’t go into the details in this blog post, but attrition is certainly not the reason telomeres shorten." I can agree that wear and tear as if by friction is not the reason telomeres shorten but the best and most common definition of attrition is not the one you chose. It's also not the one I read about in the original, peer-reviewed publications I read. I see the terms "telomere attrition" and "telomere length" (TL) most often (by far). It is clear within the context of the introduction portion of the research articles that attrition means loss without replacement.  If you're going to contrive definitions to drive your narrative I'm not inspired to read further (although I did read to the end of your linked article). The overall tone of chastisement and belittlement of the linked article ends my interest in continuing with feedback on the ability of the rest of the article to communicate.

 

People who regularly read the published literature are probably not your intended audience.

 

Wikipedia just uses the language of established scientists. Everything that sounds a bit unusual is removed instantly. 

 
But to be honest, I don't understand your point. Do you want to claim that the literature is not full of phrases such as "telomeres as protective caps," "telomeres erosion," or "telomere dysfunction"? 
 
As to Blackburn, I actually like most of her work. However, I don't see a reason for worshipping a scientist just because she received a Nobel Prize. In my article, I mention two other Nobel laureates who obviously made false claims. Just because a scientist has accomplished a lot does not mean that everything she or he publishes is true or good. You would be surprised how many false claims Albert Einstein made in established peer-viewed journals. So it should be allowed that a journalist criticizes a bad book even though a Nobel laureate wrote it. 
 
And with "feedback," I meant reaction to the factual claims in my article. For instance, is there really such a thing as "telomere attrition"? And if there is, what is wrong with my claim?

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#24 osris

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Posted 08 May 2023 - 01:20 PM

I just saw this article today:

 

"Link Between Long Telomeres and Long Life Is a Tall Tale, Study Finds"
 
 
Quote:
 
"The story, as often happens in science, sounded so appealing. Cells have a molecular clock that determines how long they live. If you can just stop the clock, cells can live indefinitely. And the same should go for people, who are, after all, made from cells. Stop the cell clocks and you can remain youthful.
 
The clocks come in the form of caps on the end of chromosomes — the long twisted strings of DNA carrying the cells’ genes. The caps on chromosomes, called telomeres, are chains of short, repeated segments of DNA. Every time a cell divides, its telomeres get a little shorter, until finally they get so short that the cell dies.
 
“Short telomeres were thought to be bad — people with premature aging syndromes had short telomeres — so, by analogy, long telomeres were thought to be good,” said Dr. Mary Armanios, professor of oncology at Johns Hopkins University School of Medicine and director of the Telomere Center at the medical school’s Sidney Kimmel Comprehensive Cancer Center. “And the longer the better.”
 
But, of course, nothing in biology is so simple. And a paper published Thursday in the New England Journal of Medicine, with results of a study that Dr. Armanios led, shows that the telomere story is no exception. While short telomeres do lead to health problems, long telomeres lead to health problems of their own. Far from extending life, long telomeres appear to cause cancer and a blood disorder known as CHIP, a condition that increases the risk of blood cancers and heart disease.
 
Dr. Elizabeth Blackburn, an emerita professor at the University of California, San Francisco, who shared a Nobel Prize for the discovery of an enzyme involved in making telomeres and who was not involved in the study, said it was a “beautiful paper” that went beyond correlations to show a direct link between long telomeres and disease. She added that the research “enlightens this whole trade-off.”
 
When scientists started studying telomeres, they observed that young people had longer ones than older people. When cells are grown in the lab, their telomeres act as sort of a ticking clock, determining how long they have to live.
 
Soon, telomeres were hailed as a secret to aging — companies advertised that they could tell your biological age by measuring the length of your telomeres. Others said that you could extend your life by preserving your telomeres with supplements.
 
But Dr. Armanios and other researchers had noticed that telomere lengths seemed constrained to a narrow range, indicating there is a price to pay for very long or very short telomeres.
 
Population studies by several groups seemed to support that idea. They found correlations — not a cause and effect — with increased disease risks at either end of the normal telomere spectrum.
 
Those with shorter than average telomeres appeared to have an increased risk of immune system problems and a variety of degenerative diseases, as well as pulmonary fibrosis, a lung disease. Those with longer than average telomeres appeared to have a modestly increased risk of cancer.
 
There were, though, some puzzlements.
 
“Some organisms have crazy long telomeres, like mice,” said Dr. Benjamin Ebert, chairman of medical oncology at the Dana-Farber Cancer Institute. “And mice don’t live that long.”
 
Dr. Armanios, as a human geneticist, thought the way to get answers was to study humans. “There are things you just can’t infer from studying cells,” she said.
 
She suspected, she said, that “you just can’t elongate telomeres without a price,” and began looking for people with very long telomeres to ask what that price might be.
 
She decided to look for people with a common genetic mutation, POT1, that can result in long telomeres. It was known to increase cancer risk but most researchers thought it was for reasons other than lengthening telomeres.
 
She ended up with 17 people from five families. They ranged in age from 7 to 83 and had extraordinarily long telomeres.
 
They also had tumors, ranging from benign, like goiters and uterine fibroids, to malignant, like those from melanoma and blood cancers. During the two-year study, four patients died of a variety of cancers.
 
Harriet Brown, 73, of Frederick, Md., is one of the study participants with very long telomeres. She has had benign tumors called paragangliomas in her neck and throat, thyroid cancer and two melanomas. She also has CHIP, the blood disorder associated with heart disease and blood cancers.
 
She has frequent scans and exams but, she said, “there is really not much I can do at this point,” because there is no way to prevent more tumors from developing.
 
The effects of long telomeres on people like Ms. Brown make perfect sense, said Dr. Norman Sharpless, professor of cancer policy and innovation at the University of North Carolina School of Medicine and a former director of the National Cancer Institute.
 
“It’s not that long telomeres make cells grow,” he said. “It’s that they don’t have the brakes to make them stop growing.” And because the telomeres of people with POT1 mutations do not grow shorter with each cell division, the cells hang around, dividing regularly. The longer they are dividing in the body, the more time they have to accumulate random mutations, some of which prompt tumor growth.
 
That’s especially true in blood, where cells are constantly being produced. POT1 mutations in some of these blood cells can give them time to accumulate other mutations that give them a selective advantage in growth. Soon some of these mutated blood cells pretty much take over a person’s bone marrow. The result is CHIP.
 
That is a new view of CHIP. The thought had been that because people with CHIP were at increased risk for blood cancer, that CHIP itself was causing cancer.
 
Instead, Dr. Armanios said, it’s that long telomeres are both creating CHIP and, independently, giving cells time to develop cancer-causing mutations.
 
“Aging biology is a lot more complicated than we’d hoped,” Dr. Sharpless said.
 
Or, as Dr. Blackburn observed: Long telomeres are not the secret to eternal youth.
 
“There is no free lunch,” she said.
 
A correction was made on May 5, 2023: An earlier version of this article misstated why Dr. Elizabeth Blackburn shared a Nobel Prize. She and other scientists discovered an enzyme involved in making telomeres, they did not discover telomeres."
 

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#25 hplus

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Posted 08 May 2023 - 04:25 PM

 

I just saw this article today:

 

"Link Between Long Telomeres and Long Life Is a Tall Tale, Study Finds"
 
 
Quote:
 
"The story, as often happens in science, sounded so appealing. Cells have a molecular clock that determines how long they live. If you can just stop the clock, cells can live indefinitely. And the same should go for people, who are, after all, made from cells. Stop the cell clocks and you can remain youthful.

 

I am curious. Did you actually read my article?



#26 hplus

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Posted 08 May 2023 - 04:27 PM

I mean this one: The (new) telomere theory of aging



#27 osris

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Posted 08 May 2023 - 04:30 PM

No, I'll read it now. The new one you just linked to. 

 


Edited by osris, 08 May 2023 - 04:53 PM.


#28 hplus

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Posted 08 May 2023 - 04:38 PM

 

Short telomeres were thought to be bad — people with premature aging syndromes had short telomeres — so, by analogy, long telomeres were thought to be good,” 

 

After reading a statement like this, it becomes apparent that the individual lacks an understanding of the correlation between the telomere countdown and the aging process. Read my article first, then we can talk. There's no point in discussing statements like the one mentioned above.

 

 


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#29 osris

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Posted 08 May 2023 - 04:53 PM

Yes, I will read your new article.

 

I just read the article you linked to in your OP, and found it interesting. You seem to be an outlier in this area. How have your ideas been received in the scientific community?


Edited by osris, 08 May 2023 - 04:54 PM.

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#30 osris

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Posted 08 May 2023 - 05:27 PM

I've read it now. I liked it. It makes sense. Here's a quote from it that is interesting:
 
"Somatic cells that no longer receive pro-geronic time signals from senescent cells adapt their epigenome by expressing rejuvenation factors and start to behave like young cells."






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