We do have mechanisms to repress transposon activity, most notably epigenetic mechanisms. Most DNA is usually tightly coiled up around little cylindrical proteins (called histones), where it can’t be easily transcribed. “Epigenetics” typically refers to modifications of the DNA and/or histones which make the coils tighter or looser, making the DNA difficult or easy to access. Most transposons are epigenetically tagged so that they’re kept tightly coiled most of the time.
These mechanisms are small interfering RNAs (siRNAs) and Piwi-interacting RNAs (piRNAs), that increase methylation of the histones associated with transposons, making them ‘tighter’, or harder to access. According to the Wikipedia page for transposon silencing, these siRNAs and piRNAs are most active in the gonads. This makes sense, as it would avoid germline transmission of active transposons, allowing offspring to be born with a lower active transposon count than their parents.
After reading that, I wondered why on earth we don’t have these transposon-suppressing RNAs coursing through our bloodstream in the same concentration as we do in our gonads. According to this paper, suppressing transposons also has the effect of suppressing neighboring genes, leading to a possible reduction in the organism’s fitness. The same paper claims that having transposons could have beneficial effects on genome evolution, as transposons create regions of suppressed recombination around them, although I don’t fully understand the reasoning behind this being good for organism fitness. Also, if suppressing transposons does have negative effects on the genome, that doesn’t at all explain why it happens more in the gonads. Perhaps aging just wasn’t selected against enough in the ancestral environment.
If nothing else, these siRNAs and piRNAs seem to be effective at making babies have fewer active transposons than their parents. If someone has injected old mice with a bunch of copies of these RNAs (probably wrapped in viruses first) and observed the results, then I can’t find their paper published anywhere. On the off chance that the transposon model is correct, and that the cure for transposon proliferation really is as simple as an RNA injection, this is one experiment we can’t afford not to do.
A couple minor expansions on this (you might know these already, but I want to make sure it’s clear to everyone else):
siRNAs and piRNAs don’t quite make babies have fewer transposons than their parents. The babies have the same number of transposons as the parents’ egg/sperm. The piRNA/siRNA activity in the egg/sperm is just higher than in other (somatic) cells to make extra sure that the transposons don’t copy before the genome is passed on.
There is a little more to it than just injecting RNAs. The RNAs would have to get into at least the cells and possibly the nucleus somehow, and also RNAs turn over quickly so the effect would not last very long. Conceptually, though, the idea is basically viable, modulo some technical hurdles.
piRNAs/siRNAs repress transposon activity, but they don’t remove existing transposons outright. So this would effectively put aging on pause, and clear up symptoms of aging, but not reverse aging. Once the administration stopped, things would bounce right back to normal.
There are some similar approaches. For instance, we could try to upregulate expression of the repression mechanisms, rather than add more RNA directly. Another approach is to directly interfere with the reverse transcription via antiretroviral drugs, e.g. lamivudine. (Retroviruses are viruses which reverse-transcribe themselves into the genome—HIV is the most notable example). This paper tested lamivudine in aged mice, and indeed found that it improved a bunch of age-related problems. (Though note that we would not expect this to remove existing transposons or even prevent damage from the endonuclease snipping the DNA if transposon count is already high; it just interferes with the reverse transcription step.)
I’m still confused. My biology knowledge is probably lacking, so maybe that’s why, but I had a similar thought to dkirmani after reading this: “Why are children born young?” Given that sperm cells are active cells (which should give transposons opportunity to divide), why do they not produce children with larger transposon counts? I would expect whatever sperm divide from to have the same accumulation of transposons that causes problems in the divisions off stem cells.
Unless piRNA and siRNA are 100% at their jobs, and nothing is explicitly removing transposons in sperm/eggs better than in the rest of the body, then surely there should be at least a small amount of accumulation of transposons across generations. Is this something we see?
I vaguely remember that women are born with all the egg cells they’ll have, so, if that’s true, then maybe that offers a partial explanation (only half the child genome should be as infected with transposons?). I’m not sure it holds water, because since egg cells are still alive, even if they aren’t dividing more, they should present opportunities for transposons to multiply.
Another possible explanation I thought of was that, in order to be as close to 100% as possible, piRNA and siRNA work more than normal in the gonads, which does hurt the efficacy of sperm, but because you only need 1 to work, that’s ok. Still, unless it is actually 100%, there should be that generational accumulation.
This isn’t even just about transposons. It feels like any theory of aging would have to contend with why sperm and eggs aren’t old when they make a child, so I’m not sure what I’m missing.
My understanding is that transposon repression mechanisms (like piRNAs) are dramatically upregulated in the germ line. They are already very close to 100% effective in most cells under normal conditions, and even more so in the germ line, so that most children do not have any more transposons than their parents.
(More generally, my understanding is that germ line cells have special stuff going to make sure that the genome is passed on with minimal errors. Non-germ cells are less “paranoid” about mutations.)
Once the rate is low enough, it’s handled by natural selection, same as any other mutations.
Unless piRNA and siRNA are 100% at their jobs, and nothing is explicitly removing transposons in sperm/eggs better than in the rest of the body, then surely there should be at least a small amount of accumulation of transposons across generations. Is this something we see?
Increase of transposons is evolutionary disadvantageous so there’s selection pressure against increased active transposon count and for reduced active transposon count.
My impression is that DNA repair mechanisms get dramatically less effective with age, and that piRNA and siRNA (and other such transposon repression mechanisms) are effective but not 100% effective even in germ cells. Since germ cells in males continue to divide through the entire lifespan, my naive expectation would be that the children of very old men to age faster than the children of younger men (not just “have worse health outcomes in general” but specifically “express the specific marks of senescence earlier”).
Is that a valid prediction of the “transposons make more transposons and eventually the exponential increase in the number of transposons kills the cell” hypothesis?
Since germ cells in males continue to divide through the entire lifespan, my naive expectation would be that the children of very old men to age faster than the children of younger men (not just “have worse health outcomes in general” but specifically “express the specific marks of senescence earlier”).
Yes, but likely a few days or months and not years.
Let’s think through a scenario.
Imagine that each human has 100 active transposons. Then imagine each additional transposon reduces the amount of raised children by 0.01. If left alone this process would reduce the active transposon count to zero. If we assume the amount of transposons that exists is in equilibirum, the amount of new transposons produced in the germline because the transposon suppression systems aren’t perfect, is exactly the amount that’s needed to keep the active transposon count on average at 100 active transposons.
Given that most of the effect of aging happen a lot later then when humans get children, it would be surprising to me when a single additional transposon would reduce the amount of raised children by 0.01. I haven’t run the numbers myself but I wouldn’t be surprised if on average there’s only one or less additional transposon per generation (at normal childbearing age).
If transposons don’t produce aging you also need to present a different mechanism of how increased transposon count produces a problem that’s big enough for evolution to keep the amount of transposons at their current level. I can’t think of a different mechanism of how transposons create the evolutionary pressure to keep their numbers in check in a organism like humans where there seems to be more transposon activity in non-germline cells.
Thanks! I changed “transposons” to “active transposons” to be more accurate. Much of my knowledge in this domain comes from a genetics course I took in the 10th grade, so it’s not super comprehensive.
piRNAs/siRNAs repress transposon activity, but they don’t remove existing transposons outright. So this would effectively put aging on pause, and clear up symptoms of aging, but not reverse aging. Once the administration stopped, things would bounce right back to normal.
My understanding was that methylated DNA stayed methylated (silenced), and methyltransferases made sure that copies of the methylated DNA sequences were also themselves methylated. If all transposons in a cell were methylated by piRNAs and siRNAs, wouldn’t all descendants of the cell also have methylated transposons, making those transposons effectively removed? (Of course, that assumes that methyltransferases and transposon-suppressing RNAs have 100% success rates, which I’m sure they don’t. This would explain why babies have a few active transposons, but not nearly as many as their parents.)
This paper asserts that piRNAs both methylate transposons, and also cleave the RNA transcripts of transposons in a cell’s cytoplasm, and that doing so guards the germline against transposons. Cleaving the transcripts of transposons would repress transposon replication in the short term, but, as I understand it, methylation of transposons would silence them in the long term, including in daughter cells. Therefore, even if there’s a one-time transposon-methylating event (as opposed to a permanent epigenetic upregulation in transposon-suppression mechanisms, which seems to be a promising idea as well), the number of active transposons in the genome should still be reduced, pushing the growth trajectory of transposons backward.
So, DNA methylation. This is another area where the things-people-typically-say seem to be completely wrong. I had also heard that methylation was long-lived (making it a natural candidate for a root cause of aging), but at one point I looked for experimental evidence on the turnover time of epigenetic methyl groups. And it turns outthat most methyl groups turn over on a timescale of ~weeks. The mechanism is enzymatic—i.e. there are enzymes constantly removing and replacing epigenetic methyl groups, so they’re in equilibrium.
I’m glad this came up, in hindsight I probably should have mentioned it in the post.
The first steps are (probably) to come up with an estimate of both material and labor costs for all 3 of the above options. The labor costs might be mostly nullified if you can find altruistic biologists, or biologists that are status-seeking and have sufficient confidence that the transposon hypothesis is true. Or if a motivated person who isn’t a biologist takes a crack at it.
The Transgenic Core guarantees that at least 300 fertilized mouse eggs will be microinjected with CRISPR/Cas9 reagents. Microinjected eggs will be transferred to pseudoopregnant female mice. Tail tip biopsies will be provided to the Investigator’s laboratory for genotyping. Mouse pups will be transferred to the investigator at weaning.
This is the service for C57BL/6 (C57 black 6) mice, the mice most commonly used as disease models, and the best-selling mice from mouse-breeding laboratories. For another $1,100, UMich will also “build CRISPR/Cas9 reagents to target a specific location in the mouse or rat genome”. So, for $7,000, one can get a founder population of transgenic mice, targeting any genome location the customer desires. Another transgenic mouse service from UMich, also for $5,800, guarantees at least 3 transgenic founder mice will be produced. ‘Founder’ implies that the actual experimental subjects will be the children of the transgenic mice you get, so you’d need to head down to PetStop and buy a few dozen hamster cages, some rodent chow, and a mouse-breeding manual.
Jackson Labs, the primary provider of experimental mice, sells C57BL/6 mice for $90 per mouse at 25 weeks old, and at $430 per mouse at 90 weeks old, with cost per mouse growing roughly linearly in between. At 25 weeks old, that’s $2,700 for 30 mice (enough for a pilot study’s control group).
There’s also the cost of shipping and handling live mice, which will vary depending on where the experiment is conducted. There are probably a bunch of auxiliary costs I haven’t considered yet as well. My main point is, as far as the Crispr route goes at least, I don’t anticipate material costs over $50,000, meaning an unofficial pilot study is probably quite doable by a small group of motivated individuals / one crazy person in a shed / crowdfunding.
In terms of experimental endpoints, would this mainly just be an experiment to see how long the mice live? If so, that does seem like a high-upside experiment which even someone with relatively little domain knowledge could just go do. The main investment would be time—it would take at least a couple years of mouse-care, and hopefully longer.
If the project were undertaken by someone with more domain expertise, the main value-add (relative to the bare-minimum version of the experiment) would probably be in checking more endpoints, especially as a debugging tool. For instance, since the CRISPR/CAS targets would presumably have very high copy number, it might be hard to get it to actually remove all the live transposons and not be saturated by dead copies which share a lot of the sequence. Checking that it actually worked would require sequencing, and special tools are needed to get accurate transposon counts from sequencing data. Also, it might require some nontrivial design to find CRISPR/CAS targets which actually work. Then there’s the possibility that CRISPR/CAS9 themselves trigger transposon derepression (they involve snipping then repairing DNA, after all), which probably wouldn’t be a game-breaker but could throw some general weirdness into things. There’s also the question of which transposons to target, since there’s a few major families and presumably a long tail of minor families...
Anyway, point is, there’s a lot of potential failure points which could be addressed with some effort and expertise. The bare-minimum version of the experiment would be huge if it worked, but if it failed, it would be hard to tell whether the theory was wrong or the experiment was flawed in some way. That said, the chance of success and the potential upside are high enough that it seems worthwhile even for the bare-minimum version.
I could imagine Constantin being interested in this—it’s not exactly the thing she set up LRI for, but it’s not a huge number of steps removed, and she’d probably at least have useful advice on how to make it happen and what to watch out for in terms of execution.
I’m also curious if anyone knows of existing groups already running this kind of experiment; I would not be surprised if it were already underway and we saw results published in another year or two (since the mice take a while to age). (More generally, do people have advice on searching for projects which have started but not published yet? I frequently stumble on them on the “projects” pages of the websites for particular labs, but I don’t know a good way to search for them.)
But new experiments are planned. For example, the team will purposely encourage expression of transposable elements to see if that undermines health and lifespan. Another approach could be to use the powerful CRISPR gene editing technique to specifically disable the ability of transposable elements to mobilize within the genome. If that intervention affected lifespan, it would be telling as well, Helfand said.
The wording is a little ambiguous as to whether the CRISPR approach is merely being contemplated, or whether they’re just floating the idea. Working with flies first makes sense, since it gives you a faster feedback loop on whether transposon elimination affects lifespan.
Stephen Helfand, the researcher quoted in the article, seems not to have published a new article since 2016, when the report I linked was published appears not to have updated his publication page since 2016, but you can find his later works on Google Scholar by searching his name (SL Helfand).
I’ve emailed him to ask whether this idea has been acted upon. I’ll post back here if I hear from him. In the meantime, I’m going to investigate the work of the followup project and the leaders associated with it.
It does look like this cluster of researchers is making progress.
Treatment of aged mice with the nucleoside reverse transcriptase inhibitor lamivudine downregulated IFN-I activation and age-associated inflammation (inflammaging) in several tissues.
Lamivudine is also called 3TC, and it’s already approved for use against HIV. A clinical trial on its efficacy against Alzheimer’s is underway and scheduled to be complete in June 2022.
(I made an account to post this)
These mechanisms are small interfering RNAs (siRNAs) and Piwi-interacting RNAs (piRNAs), that increase methylation of the histones associated with transposons, making them ‘tighter’, or harder to access. According to the Wikipedia page for transposon silencing, these siRNAs and piRNAs are most active in the gonads. This makes sense, as it would avoid germline transmission of active transposons, allowing offspring to be born with a lower active transposon count than their parents.
After reading that, I wondered why on earth we don’t have these transposon-suppressing RNAs coursing through our bloodstream in the same concentration as we do in our gonads. According to this paper, suppressing transposons also has the effect of suppressing neighboring genes, leading to a possible reduction in the organism’s fitness. The same paper claims that having transposons could have beneficial effects on genome evolution, as transposons create regions of suppressed recombination around them, although I don’t fully understand the reasoning behind this being good for organism fitness. Also, if suppressing transposons does have negative effects on the genome, that doesn’t at all explain why it happens more in the gonads. Perhaps aging just wasn’t selected against enough in the ancestral environment.
If nothing else, these siRNAs and piRNAs seem to be effective at making babies have fewer active transposons than their parents. If someone has injected old mice with a bunch of copies of these RNAs (probably wrapped in viruses first) and observed the results, then I can’t find their paper published anywhere. On the off chance that the transposon model is correct, and that the cure for transposon proliferation really is as simple as an RNA injection, this is one experiment we can’t afford not to do.
Nice comment!
A couple minor expansions on this (you might know these already, but I want to make sure it’s clear to everyone else):
siRNAs and piRNAs don’t quite make babies have fewer transposons than their parents. The babies have the same number of transposons as the parents’ egg/sperm. The piRNA/siRNA activity in the egg/sperm is just higher than in other (somatic) cells to make extra sure that the transposons don’t copy before the genome is passed on.
There is a little more to it than just injecting RNAs. The RNAs would have to get into at least the cells and possibly the nucleus somehow, and also RNAs turn over quickly so the effect would not last very long. Conceptually, though, the idea is basically viable, modulo some technical hurdles.
piRNAs/siRNAs repress transposon activity, but they don’t remove existing transposons outright. So this would effectively put aging on pause, and clear up symptoms of aging, but not reverse aging. Once the administration stopped, things would bounce right back to normal.
There are some similar approaches. For instance, we could try to upregulate expression of the repression mechanisms, rather than add more RNA directly. Another approach is to directly interfere with the reverse transcription via antiretroviral drugs, e.g. lamivudine. (Retroviruses are viruses which reverse-transcribe themselves into the genome—HIV is the most notable example). This paper tested lamivudine in aged mice, and indeed found that it improved a bunch of age-related problems. (Though note that we would not expect this to remove existing transposons or even prevent damage from the endonuclease snipping the DNA if transposon count is already high; it just interferes with the reverse transcription step.)
I’m still confused. My biology knowledge is probably lacking, so maybe that’s why, but I had a similar thought to dkirmani after reading this: “Why are children born young?” Given that sperm cells are active cells (which should give transposons opportunity to divide), why do they not produce children with larger transposon counts? I would expect whatever sperm divide from to have the same accumulation of transposons that causes problems in the divisions off stem cells.
Unless piRNA and siRNA are 100% at their jobs, and nothing is explicitly removing transposons in sperm/eggs better than in the rest of the body, then surely there should be at least a small amount of accumulation of transposons across generations. Is this something we see?
I vaguely remember that women are born with all the egg cells they’ll have, so, if that’s true, then maybe that offers a partial explanation (only half the child genome should be as infected with transposons?). I’m not sure it holds water, because since egg cells are still alive, even if they aren’t dividing more, they should present opportunities for transposons to multiply.
Another possible explanation I thought of was that, in order to be as close to 100% as possible, piRNA and siRNA work more than normal in the gonads, which does hurt the efficacy of sperm, but because you only need 1 to work, that’s ok. Still, unless it is actually 100%, there should be that generational accumulation.
This isn’t even just about transposons. It feels like any theory of aging would have to contend with why sperm and eggs aren’t old when they make a child, so I’m not sure what I’m missing.
My understanding is that transposon repression mechanisms (like piRNAs) are dramatically upregulated in the germ line. They are already very close to 100% effective in most cells under normal conditions, and even more so in the germ line, so that most children do not have any more transposons than their parents.
(More generally, my understanding is that germ line cells have special stuff going to make sure that the genome is passed on with minimal errors. Non-germ cells are less “paranoid” about mutations.)
Once the rate is low enough, it’s handled by natural selection, same as any other mutations.
Increase of transposons is evolutionary disadvantageous so there’s selection pressure against increased active transposon count and for reduced active transposon count.
My impression is that DNA repair mechanisms get dramatically less effective with age, and that piRNA and siRNA (and other such transposon repression mechanisms) are effective but not 100% effective even in germ cells. Since germ cells in males continue to divide through the entire lifespan, my naive expectation would be that the children of very old men to age faster than the children of younger men (not just “have worse health outcomes in general” but specifically “express the specific marks of senescence earlier”).
Is that a valid prediction of the “transposons make more transposons and eventually the exponential increase in the number of transposons kills the cell” hypothesis?
Yes, but likely a few days or months and not years.
Let’s think through a scenario.
Imagine that each human has 100 active transposons. Then imagine each additional transposon reduces the amount of raised children by 0.01. If left alone this process would reduce the active transposon count to zero. If we assume the amount of transposons that exists is in equilibirum, the amount of new transposons produced in the germline because the transposon suppression systems aren’t perfect, is exactly the amount that’s needed to keep the active transposon count on average at 100 active transposons.
Given that most of the effect of aging happen a lot later then when humans get children, it would be surprising to me when a single additional transposon would reduce the amount of raised children by 0.01. I haven’t run the numbers myself but I wouldn’t be surprised if on average there’s only one or less additional transposon per generation (at normal childbearing age).
If transposons don’t produce aging you also need to present a different mechanism of how increased transposon count produces a problem that’s big enough for evolution to keep the amount of transposons at their current level. I can’t think of a different mechanism of how transposons create the evolutionary pressure to keep their numbers in check in a organism like humans where there seems to be more transposon activity in non-germline cells.
Thanks! I changed “transposons” to “active transposons” to be more accurate. Much of my knowledge in this domain comes from a genetics course I took in the 10th grade, so it’s not super comprehensive.
My understanding was that methylated DNA stayed methylated (silenced), and methyltransferases made sure that copies of the methylated DNA sequences were also themselves methylated. If all transposons in a cell were methylated by piRNAs and siRNAs, wouldn’t all descendants of the cell also have methylated transposons, making those transposons effectively removed? (Of course, that assumes that methyltransferases and transposon-suppressing RNAs have 100% success rates, which I’m sure they don’t. This would explain why babies have a few active transposons, but not nearly as many as their parents.)
This paper asserts that piRNAs both methylate transposons, and also cleave the RNA transcripts of transposons in a cell’s cytoplasm, and that doing so guards the germline against transposons. Cleaving the transcripts of transposons would repress transposon replication in the short term, but, as I understand it, methylation of transposons would silence them in the long term, including in daughter cells. Therefore, even if there’s a one-time transposon-methylating event (as opposed to a permanent epigenetic upregulation in transposon-suppression mechanisms, which seems to be a promising idea as well), the number of active transposons in the genome should still be reduced, pushing the growth trajectory of transposons backward.
So, DNA methylation. This is another area where the things-people-typically-say seem to be completely wrong. I had also heard that methylation was long-lived (making it a natural candidate for a root cause of aging), but at one point I looked for experimental evidence on the turnover time of epigenetic methyl groups. And it turns out that most methyl groups turn over on a timescale of ~weeks. The mechanism is enzymatic—i.e. there are enzymes constantly removing and replacing epigenetic methyl groups, so they’re in equilibrium.
I’m glad this came up, in hindsight I probably should have mentioned it in the post.
Wow, I had no idea that methylation was that impermanent, thank you for the belief update. I guess that leaves upregulation (via acetylation?) of transposon-suppressing RNA, extending lifespan by varying expression of other genes that alter chromatin structure to be more transposon-hostile, or as this comment says, using Crispr/CAS9 to incapacitate transposons. I wonder if anyone has done/will soon do an experiment like this in mammals.
The first steps are (probably) to come up with an estimate of both material and labor costs for all 3 of the above options. The labor costs might be mostly nullified if you can find altruistic biologists, or biologists that are status-seeking and have sufficient confidence that the transposon hypothesis is true. Or if a motivated person who isn’t a biologist takes a crack at it.
UMichigan offers a transgenic mouse service for $5,800. From the item description:
This is the service for C57BL/6 (C57 black 6) mice, the mice most commonly used as disease models, and the best-selling mice from mouse-breeding laboratories. For another $1,100, UMich will also “build CRISPR/Cas9 reagents to target a specific location in the mouse or rat genome”. So, for $7,000, one can get a founder population of transgenic mice, targeting any genome location the customer desires. Another transgenic mouse service from UMich, also for $5,800, guarantees at least 3 transgenic founder mice will be produced. ‘Founder’ implies that the actual experimental subjects will be the children of the transgenic mice you get, so you’d need to head down to PetStop and buy a few dozen hamster cages, some rodent chow, and a mouse-breeding manual.
Jackson Labs, the primary provider of experimental mice, sells C57BL/6 mice for $90 per mouse at 25 weeks old, and at $430 per mouse at 90 weeks old, with cost per mouse growing roughly linearly in between. At 25 weeks old, that’s $2,700 for 30 mice (enough for a pilot study’s control group).
There’s also the cost of shipping and handling live mice, which will vary depending on where the experiment is conducted. There are probably a bunch of auxiliary costs I haven’t considered yet as well. My main point is, as far as the Crispr route goes at least, I don’t anticipate material costs over $50,000, meaning an unofficial pilot study is probably quite doable by a small group of motivated individuals / one crazy person in a shed / crowdfunding.
In terms of experimental endpoints, would this mainly just be an experiment to see how long the mice live? If so, that does seem like a high-upside experiment which even someone with relatively little domain knowledge could just go do. The main investment would be time—it would take at least a couple years of mouse-care, and hopefully longer.
If the project were undertaken by someone with more domain expertise, the main value-add (relative to the bare-minimum version of the experiment) would probably be in checking more endpoints, especially as a debugging tool. For instance, since the CRISPR/CAS targets would presumably have very high copy number, it might be hard to get it to actually remove all the live transposons and not be saturated by dead copies which share a lot of the sequence. Checking that it actually worked would require sequencing, and special tools are needed to get accurate transposon counts from sequencing data. Also, it might require some nontrivial design to find CRISPR/CAS targets which actually work. Then there’s the possibility that CRISPR/CAS9 themselves trigger transposon derepression (they involve snipping then repairing DNA, after all), which probably wouldn’t be a game-breaker but could throw some general weirdness into things. There’s also the question of which transposons to target, since there’s a few major families and presumably a long tail of minor families...
Anyway, point is, there’s a lot of potential failure points which could be addressed with some effort and expertise. The bare-minimum version of the experiment would be huge if it worked, but if it failed, it would be hard to tell whether the theory was wrong or the experiment was flawed in some way. That said, the chance of success and the potential upside are high enough that it seems worthwhile even for the bare-minimum version.
I could imagine Constantin being interested in this—it’s not exactly the thing she set up LRI for, but it’s not a huge number of steps removed, and she’d probably at least have useful advice on how to make it happen and what to watch out for in terms of execution.
I’m also curious if anyone knows of existing groups already running this kind of experiment; I would not be surprised if it were already underway and we saw results published in another year or two (since the mice take a while to age). (More generally, do people have advice on searching for projects which have started but not published yet? I frequently stumble on them on the “projects” pages of the websites for particular labs, but I don’t know a good way to search for them.)
It does sound like this research is already planned or underway.
The wording is a little ambiguous as to whether the CRISPR approach is merely being contemplated, or whether they’re just floating the idea. Working with flies first makes sense, since it gives you a faster feedback loop on whether transposon elimination affects lifespan.
Stephen Helfand,
the researcher quoted in the article, seems not to have published a new article since 2016, when the report I linked was publishedappears not to have updated his publication page since 2016, but you can find his later works on Google Scholar by searching his name (SL Helfand).I’ve emailed him to ask whether this idea has been acted upon. I’ll post back here if I hear from him. In the meantime, I’m going to investigate the work of the followup project and the leaders associated with it.
It does look like this cluster of researchers is making progress.
Lamivudine is also called 3TC, and it’s already approved for use against HIV. A clinical trial on its efficacy against Alzheimer’s is underway and scheduled to be complete in June 2022.
Bingo, thanks.
Have you thought of https://www.vium.com/ to reduce labor costs?