Bret Weinstein discusses this more fully in Evolutionary Trade-Offs: Emergent Constraints and Their Adaptive Consequences (chapter 2). Lab mice have been unintentionally selected for long telomere lengths which Weinstein argues has created skewed results compared to wild mice (or humans). Lab mice have better tissue repair capacity and greater susceptibility to tumours/cancer due to their longer telomeres.
Lab mice have better tissue repair capacity and greater susceptibility to tumours/cancer due to their longer telomeres.
There is no empirical evidence that longer telomeres increase cancer risks, and quite a bit of evidence to the contrary.
RADsays:
Read the paper, Daniel (or the original 2002 “The reserve-capacity hypothesis”). Please don’t dismiss the paper based on my quick and dirty one sentence description. In certain stages of cell growth/maintenance/repair, longer telomeres result in larger tumours. My description was not carefully worded but your counter-claim also lacks rigour.
I suspect that anyone interested in the Nature paper that you linked to will find the explanatory power of Weinstein’s paper relevant. It is not contradictory.
Yes, I know of the hypothesis that Weinstein alludes to, that senescence protects against cancer. This is a well known theory, not unique to Weinstein. What happens to this hypothesis in the lab when you test it out? Which experiments, if any, did Weinstein conduct to test it out?
We do not find that therapies to elongate telomeres increase cancer risks: the opposite is true. In this instance (link in my post), we have mice engineered to have hyper long telomeres, and again, they do not have increased cancer risks.
This appears to invalidate Weinstein’s theory.
That is, his theory would predict that the mice engineered to have really long telomeres would be more cancer prone, not less.
Weinstein’s arguments are not based on falsification but rather on hand-picked narrow examples. That is, his theory properly stated is that senescence (and telomere shortening) is anti-cancer. He points out that progeria does not lead to cancer as evidence, yet many other things might explain the protection against cancer that progeria patient enjoy, beyond senescence. That is, you need to demonstrate the progeria patients are immune to cancer because of their short telomeres.
RADsays:
Yes, I know of the hypothesis that Weinstein alludes to, that senescence protects against cancer.
That is not my understanding of Weinstein’s hypothesis. The overarching hypothesis is that many variables have tradeoffs, often antagonistic, when studied in different contexts. The different context I had in mind with telomere length involves the types of cancers that impact young(er) vertebrates (vs. senescence). Mutagens cause pre-cancerous tumour formation and telomere length limits the size. Larger pre-cancerous tumours have a higher probability of a second mutation that causes cancer. Weinstein claims that long telomere lab mice (a side-effect of breeding protocols) live in highly controlled environments that limit mutagen exposure. The theory predicts that wild mice with normal telomere length exposed to mutagens will have smaller pre-cancerous tumours and a lower incidence of cancer. The flip-side predicts that the wild mice have a lower capacity to repair tissue damaged by toxins or other factors.
I have read his chapter 2 and it is not limited to wild vs. lab mice. He makes a general prediction about short telomeres being protective against cancer.
He even makes his prediction explicit:
In any case, we predict that these cloned calves with long telomeres
will have increased cancer rates compared to sexually produced calves
raised in a similar environment (…)
He refers to calves in this passage but he means the statement to be general.
That is, he is predicting that longer telomeres translate into higher cancer rates. That simply does not pan out in reality. To my knowledge, Weinstein did not go in the lab to run the experiments. But other people have, and they get results that disagree with his prediction. Maybe more critically, the opposite appears to be true. That is, engineering animals with longer telomeres tend to reduce cancer rates. Engineering animals with short telomeres does not lead to fewer cancers.
The anti-cancer properties of telomeres are largely unproven. That is, I do not know of any effective anti-cancer therapy based on a shortening of telomeres.
This may turn out to be correct, of course… but we simply do not have the experimental evidence.
RADsays:
Ahhh…. I don’t think Weinstein emphasizes the different contexts and different cancer modes enough. In my mind, the cloned calf is exposed to real-world mutagens that the lab models are not. The long telomere cloned calf is more susceptible to mutagen induced pre-senescence cancers, compared to “normal” calves, while being less susceptible to senescence in general and senescence associated cancers. He should have qualified the cancer types and I think its important to emphasize the tradeoffs rather than a prediction about mortality overall. It is plausible that a population of long telomere calves will have lower mortality overall but I agree that empirical data is needed.
Regardless, I think the model has interesting predictive power and provides a useful perspective on the limits of lab based longevity experiments and the general problem with lab mice as models due to unintentional telomere lengthening.
Maynard Handleysays:
All that Uber data tells us is how many people tip THROUGH THE UBER APP.
Since I (and every person I know) tips in cash specifically so that the driver can keep it all …
The whole thing is a perfect example of lamppost “science”, searching where the light is strong rather than where the data is actually located.
Sean O'Connorsays:
I see the forum software messed up the indexing of the assembly language code.
Anyway you can use haddps and hsubps to do the out of place WHT in register and then some in place in register until you end up with an array of multiple 16-point WHTs, the you complete the calculation with the in place algorithm.
Anyway you should really do the code on a GPU but even buying a $100 Jetson Nano board would be an issue for me.
On a specialized chip the WHT would be extremely efficient and fast. All you need are patterns of addition and subtraction circuits and some bit shifts. Basically you would end up with a memory bandwidth problem where you calculate results faster than you can move them to and from memory.
Er, your NASA link (#10) is from 2014.
Lazarus Long must have had gigantic telomeres.
Are there any commercial services to measure telomere lengths?
“Mine is longer than yours!”
Yes, there are commercial services for measuring telomere length.mHowever, we have no evidence that measuring your telomere lengths can be a good way to predict your longevity.
Mice and telomere length
Bret Weinstein discusses this more fully in Evolutionary Trade-Offs: Emergent Constraints and Their Adaptive Consequences (chapter 2). Lab mice have been unintentionally selected for long telomere lengths which Weinstein argues has created skewed results compared to wild mice (or humans). Lab mice have better tissue repair capacity and greater susceptibility to tumours/cancer due to their longer telomeres.
Lab mice have better tissue repair capacity and greater susceptibility to tumours/cancer due to their longer telomeres.
There is no empirical evidence that longer telomeres increase cancer risks, and quite a bit of evidence to the contrary.
Read the paper, Daniel (or the original 2002 “The reserve-capacity hypothesis”). Please don’t dismiss the paper based on my quick and dirty one sentence description. In certain stages of cell growth/maintenance/repair, longer telomeres result in larger tumours. My description was not carefully worded but your counter-claim also lacks rigour.
I suspect that anyone interested in the Nature paper that you linked to will find the explanatory power of Weinstein’s paper relevant. It is not contradictory.
Yes, I know of the hypothesis that Weinstein alludes to, that senescence protects against cancer. This is a well known theory, not unique to Weinstein. What happens to this hypothesis in the lab when you test it out? Which experiments, if any, did Weinstein conduct to test it out?
We do not find that therapies to elongate telomeres increase cancer risks: the opposite is true. In this instance (link in my post), we have mice engineered to have hyper long telomeres, and again, they do not have increased cancer risks.
This appears to invalidate Weinstein’s theory.
That is, his theory would predict that the mice engineered to have really long telomeres would be more cancer prone, not less.
Weinstein’s arguments are not based on falsification but rather on hand-picked narrow examples. That is, his theory properly stated is that senescence (and telomere shortening) is anti-cancer. He points out that progeria does not lead to cancer as evidence, yet many other things might explain the protection against cancer that progeria patient enjoy, beyond senescence. That is, you need to demonstrate the progeria patients are immune to cancer because of their short telomeres.
That is not my understanding of Weinstein’s hypothesis. The overarching hypothesis is that many variables have tradeoffs, often antagonistic, when studied in different contexts. The different context I had in mind with telomere length involves the types of cancers that impact young(er) vertebrates (vs. senescence). Mutagens cause pre-cancerous tumour formation and telomere length limits the size. Larger pre-cancerous tumours have a higher probability of a second mutation that causes cancer. Weinstein claims that long telomere lab mice (a side-effect of breeding protocols) live in highly controlled environments that limit mutagen exposure. The theory predicts that wild mice with normal telomere length exposed to mutagens will have smaller pre-cancerous tumours and a lower incidence of cancer. The flip-side predicts that the wild mice have a lower capacity to repair tissue damaged by toxins or other factors.
I have read his chapter 2 and it is not limited to wild vs. lab mice. He makes a general prediction about short telomeres being protective against cancer.
He even makes his prediction explicit:
He refers to calves in this passage but he means the statement to be general.
That is, he is predicting that longer telomeres translate into higher cancer rates. That simply does not pan out in reality. To my knowledge, Weinstein did not go in the lab to run the experiments. But other people have, and they get results that disagree with his prediction. Maybe more critically, the opposite appears to be true. That is, engineering animals with longer telomeres tend to reduce cancer rates. Engineering animals with short telomeres does not lead to fewer cancers.
The anti-cancer properties of telomeres are largely unproven. That is, I do not know of any effective anti-cancer therapy based on a shortening of telomeres.
This may turn out to be correct, of course… but we simply do not have the experimental evidence.
Ahhh…. I don’t think Weinstein emphasizes the different contexts and different cancer modes enough. In my mind, the cloned calf is exposed to real-world mutagens that the lab models are not. The long telomere cloned calf is more susceptible to mutagen induced pre-senescence cancers, compared to “normal” calves, while being less susceptible to senescence in general and senescence associated cancers. He should have qualified the cancer types and I think its important to emphasize the tradeoffs rather than a prediction about mortality overall. It is plausible that a population of long telomere calves will have lower mortality overall but I agree that empirical data is needed.
Regardless, I think the model has interesting predictive power and provides a useful perspective on the limits of lab based longevity experiments and the general problem with lab mice as models due to unintentional telomere lengthening.
All that Uber data tells us is how many people tip THROUGH THE UBER APP.
Since I (and every person I know) tips in cash specifically so that the driver can keep it all …
The whole thing is a perfect example of lamppost “science”, searching where the light is strong rather than where the data is actually located.
I see the forum software messed up the indexing of the assembly language code.
Anyway you can use haddps and hsubps to do the out of place WHT in register and then some in place in register until you end up with an array of multiple 16-point WHTs, the you complete the calculation with the in place algorithm.
Anyway you should really do the code on a GPU but even buying a $100 Jetson Nano board would be an issue for me.
On a specialized chip the WHT would be extremely efficient and fast. All you need are patterns of addition and subtraction circuits and some bit shifts. Basically you would end up with a memory bandwidth problem where you calculate results faster than you can move them to and from memory.