12 ms·

Telomere lengthening via gene therapy in a human individual

287 points by mkagenius 11y ago

reasonattlm 11y ago
From BioViva: http://bioviva-science.com/2016/04/21/first-gene-therapy-successful-against-human-aging/ http://bioviva-science.com/2016/04/21/first-gene-therapy-suc... They are a startup in their funding-press-funding-doing-things-press-funding cycle, so expect a certain amount of positioning. This is all serious work, however. Deep Knowledge Life Sciences recently took a position, so BioViva is within the circle that includes the reputable In Silico Medicine, Biogerontology Research Foundation, and other for- and non-profit groups in life science and aging research and advocacy: http://www.eurekalert.org/pub_releases/2016-04/brf-dkl041916.php http://www.eurekalert.org/pub_releases/2016-04/brf-dkl041916... Take a look at the BioViva board of advisors, and note the presence of George Church, who is essentially the center of the network of connections for all gene therapy activities these days, and a luminary in the field. The nature of the BioViva press here is that they did a thing, and the thing worked as expected based on the only available way to take a short-term measurement. That seems quite a reasonable thing to announce when you are a young company working on traction. It doesn't really imply rejuvenation without more useful data, such as DNA methylation assays of biological age, for example, and the details on that front are complicated, see below. Telomerase gene therapies to treat aging are heading for human trials one way or another. Look at this position paper for example, from one of the groups to have demonstrated improved health, stem cell function, and longevity in mice using telomerase gene therapies in past years: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4815611/ http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4815611/ BioViva's principals are taking the stance that present regulation and talk of moratoriums are ridiculous given the fact that so much good might be done, and that new gene therapy technologies such as CRISPR are now making it cheap and easy to run these sorts of edits in humans. I agree with this. So telomerase gene therapy in mice extends life modestly: there are years of pretty robust results to demonstrate that. Average telomere length appears to be a reflection of aging, most likely not a significant contributer to aging. It is a poor measure, as the trend downward with age is statistical over populations. Average telomere length is some function of stem cell activity (delivering new cells with long telomeres) and cell division rates (shortening telomeres with each division). Stem cell activity declines with aging. Average telomere length is presently measured in white blood cells, which are going to have a whole lot of influences on cell division and replacement rates that don't exist in other tissues, due to immune system reactions to circumstances. Telomerase is clearly doing a lot of other things beyond telomere lengthening. Look at the work suggesting it is acting as a mitochondrial antioxidant, for example, or other cryptic activities. The present consensus is that telomerase therapies in mice extend life through increased stem cell and/or immune activity. Mice have very different telomere dynamics, however, and there are concerns regarding cancer risk in humans. Trying it in dogs or primates would be the next safe thing to do - move to a mammalian species with telomere/telomerase dynamics that are closer to ours. There is an argument that runs along these lines: telomerase gene therapy is just (primarily) another way of triggering old stem cells to get back to work, and therefore vis a vis cancer and risk should fall in the same ballpark as stem cell therapies carried out over the past fifteen years, and therefore full steam ahead because all of that work produced far less cancer that was feared. Prudence would suggest trying it out in something other than mice first, but I suspect the sudden ease of gene therapy means that this will be bypassed by the adventurous. I'm totally in favor of adventure when it comes to gene therapies for follistatin/myostatin - I think the risk situation there is pretty much as low as it can get prior to hundreds or thousands of enhanced human patients. I'm more cautious on the cancer and telomerase front; I think more data there would be desirable before I stepped up to try it out. Other people can have other viewpoints, and that is the point - it should be the patient's informed decision, not that of a bunch of self-interested bureaucrats.
- forloop 11y ago
  They fixed their RSS feed—for their blog—a few days ago, so I ended up on the site (having previously subscribed). It was interesting to see they're looking at using the therapy for other conditions. Do you know if there's any scope for doing something to reduce cancer risk, with this tech? Such as enhancing P53, or something like that (if that doesn't damage the individual).
  - reasonattlm 11y ago
    One of the GRG regulars raised the suggestion that perhaps we don't see increased cancer risk in mice following telomerase therapy - and that's after the research group in question dropped the addition of tinkering with P53, and moved to straight telomerase overexpression, interestingly - because the immune system improvement means that there is more and better cancer immunosurveillance going on. I'm not aware of any earnest data to support or contradict that hypothesis, however.
    - forloop 11y ago
      Thanks!
    - lunula 11y ago
      What's GRG? Do you have a link to the comment?
      - reasonattlm 11y ago
        The Gerontology Research Group, originally organized by the late Stephen Coles. The mailing list is a watering hole of sorts for the gerontology community and some of the surrounding advocates and entrepreneurs, though much less so now than used to be the case. It is a closed list, so no link, I'm afraid.
- forloop 11y ago
  There's a vid of George Church talking at length on edge.org[0]. As with all edge.org vids, it's profound. [0] https://www.edge.org/conversation/george_church-the-augmented-human-being https://www.edge.org/conversation/george_church-the-augmente...
deleted 11y ago
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charlesism 11y ago
Thanks to mkagenius for using a reasonable title. Sadly, the actual article went with the tabloid-style "First Gene Therapy Successful Against Human Aging."
- meeper16 11y ago
  "... Successful Against Aging in White Cells in a Human" would be more accurate while also preserving the informative aspect. Most people don't know that Telomeres directly connect to human aging.
  - charlesism 11y ago
    "Most people don't know that Telomeres directly connect to human aging." As far as I know, it isn't entirely settled that they do ...which is why the title is misleading. I guess it will be hard to argue against if Elizabeth Parish pulls a Benjamin Button.
  - blater 11y ago
    Not sure about that with the HN audience. I have only the most passing interest in biology and aging research but I automatically made the association.
  - rasengan 11y ago
    Anyone that watched Gundam Seed Destiny does. :)
ozborn 11y ago
A good article, but if you take a look at the 7 problems that SENS "Strategies for Engineered Negligible Senescence" identifies as needing to be solved to address ageing the telomere length issue is just one subset of single issue (cellular senescence). Furthermore they appear to have fixed this only for a single cell type - white blood cells which are easy to obtain and do gene therapy on. Nonetheless it is still encouraging progress...
- patall 11y ago
  I disagree. This is not a good article, it does not state anything (what kind of genetherapy, what kind of gene, how was it administered) but wants to tell a personal story. You can not even say how they achieved longer telomeres in white blood cells. Have they transduced hematopoetic stem cells? Or just transplanted (some kind of) white blood cells, that will be gone from the body in a few months? That would not be progress.
zavi 11y ago
Hats off to brave Elizabeth Parrish who put her life at risk to push humanity forward. People were dismissing her as a lunatic at the time of treatment administration. Now independently verified results speak for themselves.
- patall 11y ago
  If it is true what is written in this pr articel, she is an even bigger lunatic then previously thought. You do not treat someone with two experimental treatments at the same time, that is unscientific to the power of five. How would you determine which treatment was successfull and which was not (well, Phase I is about side effects, but you still need to distinguish)? Highly controversal.
  - CuriouslyC 11y ago
    It doesn't matter how many hypotheses you test at one time, as long as they are all orthogonal. The problem arises when attempting to test multiple hypotheses that have some co-linearity in the solution.
    - SCHiM 11y ago
      But you don't know that going in do you? If you knew exactly what was going to happen you wouldn't need to experiment in the first place.
    - aidenn0 11y ago
      And it's not always possible to tell which hypotheses are orthogonal; if you test two hypotheses at once that you believe to be orthogonal, but it turns out that there is some underlying connection between them, you will get bogus results.
    - lunula 11y ago
      Here the co-linearity is that of them being applied to the same body. Now, I think it is still useful. At the first you always have N of one, and obviously there is no control. We at least know you don't die right away when your WBCs are upgraded.
meeper16 11y ago
I wonder what Google's CalicoLabs http://calicolabs.com http://calicolabs.com thinks about this...
tosseraccount 11y ago
Two thoughts .. #1 No details of the "gene therapy". Did they paste telomerase genes into a virus, infect white blood cells and re-inject them? #2 Telomeric lengthening can be a double edge sword. You don't want all your cells to live forever ... particularly in things like cancer cells.
- crusso 11y ago
  On #2, they're lengthening telomeres, not disabling the telomere mechanism. I'd think that one of the first mutations a cell needs to undergo on the road to being considered "cancerous" is to completely disable the telomere mechanism so that it will become immortal.
  - dghughes 11y ago
    Long telomeres are necessarily better in fact it increases the risk of cancers. Too short is bad, too long is bad.
- reasonattlm 11y ago
  There are some details in the AMA that Parrish hosted, but not the specific technique or vector used. One can probably make educated guesses based on who was involved and their past work. It was a whole-body approach, not targeted to any specific tissue. Telomere length was measured in white blood cells because that is the present standard assay in the scientific community, not because immune cells were targeted specifically: https://www.reddit.com/r/Futurology/comments/3ocsbi/ama_my_name_is_liz_parrish_ceo_of_bioviva_the/ https://www.reddit.com/r/Futurology/comments/3ocsbi/ama_my_n... "The genes targeted are human telomerase reverse transcriptase (hTERT) and follistatin (FST). In animal models neither FST nor hTERT have increased the risk of cancer. We expect to see the same result on myself, and to that effect we are measuring all known cancer biomarkers. The gene therapies on my body are to measure the effects on humans. There is plenty of animal research to support these gene therapies but no one was conducting human tests. We are using both visual biomarkers, MRI and a panel of blood and tissue testing including work on telomere length and epigenetic testing. We are collecting as much data as we can, but unfortunately we currently don't have the coverage rate for this therapy, how much of the tissue of the body is affected. Depending on the tissue and vector used we ultimately expect to see similar rates of transfection as seen in mice, which is somewhere between 5 to 60%."
bitL 11y ago
The link between telomere shortening and age was proved just a typical correlation recently; in fact telomere can expand naturally as well. Might not be as useful as she thought... By the way, is there any attempt for a programming language of human body on biochemical level? Programming protein/DNA/RNA interactions as a form of language? Currently all our efforts seem to be like hacking by shooting blanks, or as if you changed/inserted/deleted a few lines of code randomly and observed what that does (typically on animals).
- ganeumann 11y ago
  > By the way, is there any attempt for a programming language of human body on biochemical level? Not quite, but there are languages that allow you to create organisms using known proteins, etc. https://moleculamaxima.com/ https://moleculamaxima.com/ for example.
- nickthemagicman 11y ago
  We don't really understand the "hardware" enough to create a legit programming language for life yet. We're basically reverse engineering biology and that's pretty hard. Believe it or not DNA/RNA knowledge is just the tip of the iceberg in how life works. There's so many other factors that influence DNA expression like DNA folding/compaction, enzyme up/down regulation, the genes environment, all in a vary complex interacting system that creates life as we know it. If you want to skip the DNA and jump straight to proteins and just start assembling amino acids then you run into an NP hard problem that the most advanced supercomputers and GPU clusters can't decipher. So that's a brief summary into the challenges that are faced. If we ever do reverse engineer life I think we would become what historic literature classifies as "Gods".
  - megalodon 11y ago
    Yep, and most interactions are non-deterministic. I think we can safely say it won't happen in our lifetime. On the bright side, we have a lot to learn and learning is life :)
    - 11y ago
deleted 11y ago
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seanwilson 11y ago
> Telomeres are short segments of DNA which cap the ends of every chromosome, acting as 'buffers' against wear and tear. They shorten with every cell division, eventually getting too short to protect the chromosome, causing the cell to malfunction and the body to age. Can anyone explain what happens to telomere length when a new human is born? Presumably the telomere length is reset? Is there a beneficial reason for telomeres shortening with time?
- 8note 11y ago
  > Is there a beneficial reason for telomeres shortening with time? So that people die instead of reproducing when they're old
  - nanofortnight 11y ago
    It is also the final defense against unrestrained cell divison; a natural protection against diseases such as cancer.
  - estefan 11y ago
    There were cultures where the oldest men in the tribe got exclusivity over the teenage girls to reproduce with. Also, since men can reproduce in old age, that sounds questionable to me.
  - dsjoerg 11y ago
    So that people die when they're no longer reproductively viable / relevant, rather than using up valuable resources. Wouldn't telomere shortening have some selection-pressure advantage?
- maxander 11y ago
  Indeed, in gametes (sperm and egg cells) the cells use enzymes that rebuild telomeres. Telomeres "shorten" when DNA is copied for cell replication; the benefit of this is that it means telomeres quickly whittle down to nothing, and kill the resulting cells, when a rogue cell line has started replicating an unnecessary number of times- e.g., in cancer.
kumarski 11y ago
I've gotten about 60 messages about Liz Parrish's outfit and the test on herself to lengthen her telomeres. I don't think there's any substance to any of her claims and life extension. A few very critical questions: 1/ What if anything does telomere lengthening have to do with life extension? (It's multi-factorial) Correlation is not causation.. See: https://www.ncbi.nlm.nih.gov/pubmed/25862531 https://www.ncbi.nlm.nih.gov/pubmed/25862531 2/ Why did she use a lab that's on quackwatch to do the tests? (http://www.quackwatch.org/01QuackeryRela…/…/nonstandard.html http://www.quackwatch.org/01QuackeryRela…/…/nonstandard.html) 3/ Haven't we already proven telomere lengthening and muscle hacks in animal models? 4/ What type of AAV is she using to transfect her cells with telomerase? (Take a look at the animal studies: http://www.nature.com/mt/journal/v18/n3/full/mt2009286a.html http://www.nature.com/mt/journal/v18/n3/full/mt2009286a.html, http://virologyj.biomedcentral.com/…/10.1186/1743-422X-10-74 http://virologyj.biomedcentral.com/…/10.1186/1743-422X-10-74) 5/ How many cells had their telomeres lengthened? (I bet you it was a petty amount.....100 to 1 says they're not all that good at actually delivering genes) There's actual chemists/biologists busting their ass at places like genentech and top research universities to solve missing mendelian inheritance the long difficult way. They're true pioneers staring down the barrel of a gun loaded with the world's most difficult NP-Hard problems. This Parrish outfit steals their thunder. Aging isn't something you can simply disrupt with a silicon valley mindset. I've met organic chemists who have spent upwards of 30 years developing drugs and haven't put a single drug on the market. Their work was still super valuable.
- blazespin 11y ago
  Nah, it's all good. These random people have their place. I think the problem isn't so much Liz and her friends but rather that people take them too seriously. I think for the most part, they're doing great work and the world would be less of a place without them. Just we shouldn't expect so much. It's like VC. Only about 1 in 100 actually go somewhere big.
- fthssht 11y ago
  #3 actually seems positive.
- imaginenore 11y ago
wavesum 11y ago
I'd be suspicious of an article written by a Company about a study the Company conducted about a miracle cure developed by the Company and tested by the CEO of the Company. http://bioviva-science.com/2016/04/21/first-gene-therapy-successful-against-human-aging/ http://bioviva-science.com/2016/04/21/first-gene-therapy-suc...
pamelabuck 11y ago
There's little causality but just correlation in telomere and lifespan.
kumarski 11y ago
My molecular biologist friend's comment on this is pretty on-point, so I though it was worth sharing: This is one of the first gene therapy studies I've seen that didn't end with "but we accidentally gave our subjects aggressive leukemias, whoops". Extending telomeres is interesting! And there's a lot of good data that critically short telomeres can lead to and cause cellular senescence and death. But telomeres are just end-caps of entire chromosomes worth of DNA. They are interesting with regards to aging partly just because they are measurable and quantifiable, but aging is so much more complicated and multifactorial than just telomere length, that manipulating telomere length and saying this solves aging is an overstatement. Cancers can express telomerase and immortalize themselves just fine, for example. Manipulating telomeres to investigate aging reminds me of this classic joke. A cop pulls up late at night to a biologist slowly walking a spiral around a streetlight, staring at the ground intently. "Uh, sir," says the cop, "what are you doing?" "Looking for my keys," replies the biologist. "I dropped them somewhere on this street. "I see," says the cop. "But why are you just looking around this light?" "Light's better here", he replies.
- joeyspn 11y ago
  > My molecular biologist friend's comment on this [...] Manipulating telomeres to investigate aging reminds me of this classic joke [...] What's your friend speciality? Any link to his telomeres/telomerase papers, or any chance you can point him to Maria Blasco's [0] work (top researcher in the field with 200+ papers [1]) for comments?: It'd be interesting to see science-backed rebuttals. [0] https://en.wikipedia.org/wiki/Mar%C3%ADa_Blasco_Marhuenda https://en.wikipedia.org/wiki/Mar%C3%ADa_Blasco_Marhuenda [1] https://scholar.google.es/scholar?q=MA+blasco&hl=en&as_sdt=0 https://scholar.google.es/scholar?q=MA+blasco&hl=en&as_sdt=0
jstewartmobile 11y ago
It's Theranos all over again, with lower stakes.

287 points by mkagenius 11y ago

From BioViva: http://bioviva-science.com/2016/04/21/first-gene-therapy-successful-against-human-aging/ http://bioviva-science.com/2016/04/21/first-gene-therapy-suc... They are a startup in their funding-press-funding-doing-things-press-funding cycle, so expect a certain amount of positioning. This is all serious work, however. Deep Knowledge Life Sciences recently took a position, so BioViva is within the circle that includes the reputable In Silico Medicine, Biogerontology Research Foundation, and other for- and non-profit groups in life science and aging research and advocacy: http://www.eurekalert.org/pub_releases/2016-04/brf-dkl041916.php http://www.eurekalert.org/pub_releases/2016-04/brf-dkl041916... Take a look at the BioViva board of advisors, and note the presence of George Church, who is essentially the center of the network of connections for all gene therapy activities these days, and a luminary in the field. The nature of the BioViva press here is that they did a thing, and the thing worked as expected based on the only available way to take a short-term measurement. That seems quite a reasonable thing to announce when you are a young company working on traction. It doesn't really imply rejuvenation without more useful data, such as DNA methylation assays of biological age, for example, and the details on that front are complicated, see below. Telomerase gene therapies to treat aging are heading for human trials one way or another. Look at this position paper for example, from one of the groups to have demonstrated improved health, stem cell function, and longevity in mice using telomerase gene therapies in past years: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4815611/ http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4815611/ BioViva's principals are taking the stance that present regulation and talk of moratoriums are ridiculous given the fact that so much good might be done, and that new gene therapy technologies such as CRISPR are now making it cheap and easy to run these sorts of edits in humans. I agree with this. So telomerase gene therapy in mice extends life modestly: there are years of pretty robust results to demonstrate that. Average telomere length appears to be a reflection of aging, most likely not a significant contributer to aging. It is a poor measure, as the trend downward with age is statistical over populations. Average telomere length is some function of stem cell activity (delivering new cells with long telomeres) and cell division rates (shortening telomeres with each division). Stem cell activity declines with aging. Average telomere length is presently measured in white blood cells, which are going to have a whole lot of influences on cell division and replacement rates that don't exist in other tissues, due to immune system reactions to circumstances. Telomerase is clearly doing a lot of other things beyond telomere lengthening. Look at the work suggesting it is acting as a mitochondrial antioxidant, for example, or other cryptic activities. The present consensus is that telomerase therapies in mice extend life through increased stem cell and/or immune activity. Mice have very different telomere dynamics, however, and there are concerns regarding cancer risk in humans. Trying it in dogs or primates would be the next safe thing to do - move to a mammalian species with telomere/telomerase dynamics that are closer to ours. There is an argument that runs along these lines: telomerase gene therapy is just (primarily) another way of triggering old stem cells to get back to work, and therefore vis a vis cancer and risk should fall in the same ballpark as stem cell therapies carried out over the past fifteen years, and therefore full steam ahead because all of that work produced far less cancer that was feared. Prudence would suggest trying it out in something other than mice first, but I suspect the sudden ease of gene therapy means that this will be bypassed by the adventurous. I'm totally in favor of adventure when it comes to gene therapies for follistatin/myostatin - I think the risk situation there is pretty much as low as it can get prior to hundreds or thousands of enhanced human patients. I'm more cautious on the cancer and telomerase front; I think more data there would be desirable before I stepped up to try it out. Other people can have other viewpoints, and that is the point - it should be the patient's informed decision, not that of a bunch of self-interested bureaucrats.

forloop 11y ago
They fixed their RSS feed—for their blog—a few days ago, so I ended up on the site (having previously subscribed). It was interesting to see they're looking at using the therapy for other conditions. Do you know if there's any scope for doing something to reduce cancer risk, with this tech? Such as enhancing P53, or something like that (if that doesn't damage the individual).
- reasonattlm 11y ago
  One of the GRG regulars raised the suggestion that perhaps we don't see increased cancer risk in mice following telomerase therapy - and that's after the research group in question dropped the addition of tinkering with P53, and moved to straight telomerase overexpression, interestingly - because the immune system improvement means that there is more and better cancer immunosurveillance going on. I'm not aware of any earnest data to support or contradict that hypothesis, however.
  - forloop 11y ago
    Thanks!
  - lunula 11y ago
    What's GRG? Do you have a link to the comment?
    - reasonattlm 11y ago
      The Gerontology Research Group, originally organized by the late Stephen Coles. The mailing list is a watering hole of sorts for the gerontology community and some of the surrounding advocates and entrepreneurs, though much less so now than used to be the case. It is a closed list, so no link, I'm afraid.
forloop 11y ago
There's a vid of George Church talking at length on edge.org[0]. As with all edge.org vids, it's profound. [0] https://www.edge.org/conversation/george_church-the-augmented-human-being https://www.edge.org/conversation/george_church-the-augmente...

deleted 11y ago

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charlesism 11y ago

Thanks to mkagenius for using a reasonable title. Sadly, the actual article went with the tabloid-style "First Gene Therapy Successful Against Human Aging."

meeper16 11y ago
"... Successful Against Aging in White Cells in a Human" would be more accurate while also preserving the informative aspect. Most people don't know that Telomeres directly connect to human aging.
- charlesism 11y ago
  "Most people don't know that Telomeres directly connect to human aging." As far as I know, it isn't entirely settled that they do ...which is why the title is misleading. I guess it will be hard to argue against if Elizabeth Parish pulls a Benjamin Button.
- blater 11y ago
  Not sure about that with the HN audience. I have only the most passing interest in biology and aging research but I automatically made the association.
- rasengan 11y ago
  Anyone that watched Gundam Seed Destiny does. :)

ozborn 11y ago

A good article, but if you take a look at the 7 problems that SENS "Strategies for Engineered Negligible Senescence" identifies as needing to be solved to address ageing the telomere length issue is just one subset of single issue (cellular senescence). Furthermore they appear to have fixed this only for a single cell type - white blood cells which are easy to obtain and do gene therapy on. Nonetheless it is still encouraging progress...

patall 11y ago
I disagree. This is not a good article, it does not state anything (what kind of genetherapy, what kind of gene, how was it administered) but wants to tell a personal story. You can not even say how they achieved longer telomeres in white blood cells. Have they transduced hematopoetic stem cells? Or just transplanted (some kind of) white blood cells, that will be gone from the body in a few months? That would not be progress.

zavi 11y ago

Hats off to brave Elizabeth Parrish who put her life at risk to push humanity forward. People were dismissing her as a lunatic at the time of treatment administration. Now independently verified results speak for themselves.

patall 11y ago
If it is true what is written in this pr articel, she is an even bigger lunatic then previously thought. You do not treat someone with two experimental treatments at the same time, that is unscientific to the power of five. How would you determine which treatment was successfull and which was not (well, Phase I is about side effects, but you still need to distinguish)? Highly controversal.
- CuriouslyC 11y ago
  It doesn't matter how many hypotheses you test at one time, as long as they are all orthogonal. The problem arises when attempting to test multiple hypotheses that have some co-linearity in the solution.
  - SCHiM 11y ago
    But you don't know that going in do you? If you knew exactly what was going to happen you wouldn't need to experiment in the first place.
  - aidenn0 11y ago
    And it's not always possible to tell which hypotheses are orthogonal; if you test two hypotheses at once that you believe to be orthogonal, but it turns out that there is some underlying connection between them, you will get bogus results.
  - lunula 11y ago
    Here the co-linearity is that of them being applied to the same body. Now, I think it is still useful. At the first you always have N of one, and obviously there is no control. We at least know you don't die right away when your WBCs are upgraded.

meeper16 11y ago

I wonder what Google's CalicoLabs http://calicolabs.com http://calicolabs.com thinks about this...

tosseraccount 11y ago

Two thoughts .. #1 No details of the "gene therapy". Did they paste telomerase genes into a virus, infect white blood cells and re-inject them? #2 Telomeric lengthening can be a double edge sword. You don't want all your cells to live forever ... particularly in things like cancer cells.

crusso 11y ago
On #2, they're lengthening telomeres, not disabling the telomere mechanism. I'd think that one of the first mutations a cell needs to undergo on the road to being considered "cancerous" is to completely disable the telomere mechanism so that it will become immortal.
- dghughes 11y ago
  Long telomeres are necessarily better in fact it increases the risk of cancers. Too short is bad, too long is bad.
reasonattlm 11y ago
There are some details in the AMA that Parrish hosted, but not the specific technique or vector used. One can probably make educated guesses based on who was involved and their past work. It was a whole-body approach, not targeted to any specific tissue. Telomere length was measured in white blood cells because that is the present standard assay in the scientific community, not because immune cells were targeted specifically: https://www.reddit.com/r/Futurology/comments/3ocsbi/ama_my_name_is_liz_parrish_ceo_of_bioviva_the/ https://www.reddit.com/r/Futurology/comments/3ocsbi/ama_my_n... "The genes targeted are human telomerase reverse transcriptase (hTERT) and follistatin (FST). In animal models neither FST nor hTERT have increased the risk of cancer. We expect to see the same result on myself, and to that effect we are measuring all known cancer biomarkers. The gene therapies on my body are to measure the effects on humans. There is plenty of animal research to support these gene therapies but no one was conducting human tests. We are using both visual biomarkers, MRI and a panel of blood and tissue testing including work on telomere length and epigenetic testing. We are collecting as much data as we can, but unfortunately we currently don't have the coverage rate for this therapy, how much of the tissue of the body is affected. Depending on the tissue and vector used we ultimately expect to see similar rates of transfection as seen in mice, which is somewhere between 5 to 60%."

bitL 11y ago

The link between telomere shortening and age was proved just a typical correlation recently; in fact telomere can expand naturally as well. Might not be as useful as she thought... By the way, is there any attempt for a programming language of human body on biochemical level? Programming protein/DNA/RNA interactions as a form of language? Currently all our efforts seem to be like hacking by shooting blanks, or as if you changed/inserted/deleted a few lines of code randomly and observed what that does (typically on animals).

ganeumann 11y ago
> By the way, is there any attempt for a programming language of human body on biochemical level? Not quite, but there are languages that allow you to create organisms using known proteins, etc. https://moleculamaxima.com/ https://moleculamaxima.com/ for example.
nickthemagicman 11y ago
We don't really understand the "hardware" enough to create a legit programming language for life yet. We're basically reverse engineering biology and that's pretty hard. Believe it or not DNA/RNA knowledge is just the tip of the iceberg in how life works. There's so many other factors that influence DNA expression like DNA folding/compaction, enzyme up/down regulation, the genes environment, all in a vary complex interacting system that creates life as we know it. If you want to skip the DNA and jump straight to proteins and just start assembling amino acids then you run into an NP hard problem that the most advanced supercomputers and GPU clusters can't decipher. So that's a brief summary into the challenges that are faced. If we ever do reverse engineer life I think we would become what historic literature classifies as "Gods".
- megalodon 11y ago
  Yep, and most interactions are non-deterministic. I think we can safely say it won't happen in our lifetime. On the bright side, we have a lot to learn and learning is life :)
  - 11y ago

deleted 11y ago

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seanwilson 11y ago

> Telomeres are short segments of DNA which cap the ends of every chromosome, acting as 'buffers' against wear and tear. They shorten with every cell division, eventually getting too short to protect the chromosome, causing the cell to malfunction and the body to age. Can anyone explain what happens to telomere length when a new human is born? Presumably the telomere length is reset? Is there a beneficial reason for telomeres shortening with time?

8note 11y ago
> Is there a beneficial reason for telomeres shortening with time? So that people die instead of reproducing when they're old
- nanofortnight 11y ago
  It is also the final defense against unrestrained cell divison; a natural protection against diseases such as cancer.
- estefan 11y ago
  There were cultures where the oldest men in the tribe got exclusivity over the teenage girls to reproduce with. Also, since men can reproduce in old age, that sounds questionable to me.
- dsjoerg 11y ago
  So that people die when they're no longer reproductively viable / relevant, rather than using up valuable resources. Wouldn't telomere shortening have some selection-pressure advantage?
maxander 11y ago
Indeed, in gametes (sperm and egg cells) the cells use enzymes that rebuild telomeres. Telomeres "shorten" when DNA is copied for cell replication; the benefit of this is that it means telomeres quickly whittle down to nothing, and kill the resulting cells, when a rogue cell line has started replicating an unnecessary number of times- e.g., in cancer.

kumarski 11y ago

I've gotten about 60 messages about Liz Parrish's outfit and the test on herself to lengthen her telomeres. I don't think there's any substance to any of her claims and life extension. A few very critical questions: 1/ What if anything does telomere lengthening have to do with life extension? (It's multi-factorial) Correlation is not causation.. See: https://www.ncbi.nlm.nih.gov/pubmed/25862531 https://www.ncbi.nlm.nih.gov/pubmed/25862531 2/ Why did she use a lab that's on quackwatch to do the tests? (http://www.quackwatch.org/01QuackeryRela…/…/nonstandard.html http://www.quackwatch.org/01QuackeryRela…/…/nonstandard.html) 3/ Haven't we already proven telomere lengthening and muscle hacks in animal models? 4/ What type of AAV is she using to transfect her cells with telomerase? (Take a look at the animal studies: http://www.nature.com/mt/journal/v18/n3/full/mt2009286a.html http://www.nature.com/mt/journal/v18/n3/full/mt2009286a.html, http://virologyj.biomedcentral.com/…/10.1186/1743-422X-10-74 http://virologyj.biomedcentral.com/…/10.1186/1743-422X-10-74) 5/ How many cells had their telomeres lengthened? (I bet you it was a petty amount.....100 to 1 says they're not all that good at actually delivering genes) There's actual chemists/biologists busting their ass at places like genentech and top research universities to solve missing mendelian inheritance the long difficult way. They're true pioneers staring down the barrel of a gun loaded with the world's most difficult NP-Hard problems. This Parrish outfit steals their thunder. Aging isn't something you can simply disrupt with a silicon valley mindset. I've met organic chemists who have spent upwards of 30 years developing drugs and haven't put a single drug on the market. Their work was still super valuable.

blazespin 11y ago
Nah, it's all good. These random people have their place. I think the problem isn't so much Liz and her friends but rather that people take them too seriously. I think for the most part, they're doing great work and the world would be less of a place without them. Just we shouldn't expect so much. It's like VC. Only about 1 in 100 actually go somewhere big.
fthssht 11y ago
#3 actually seems positive.
imaginenore 11y ago

wavesum 11y ago

I'd be suspicious of an article written by a Company about a study the Company conducted about a miracle cure developed by the Company and tested by the CEO of the Company. http://bioviva-science.com/2016/04/21/first-gene-therapy-successful-against-human-aging/ http://bioviva-science.com/2016/04/21/first-gene-therapy-suc...

pamelabuck 11y ago

There's little causality but just correlation in telomere and lifespan.

kumarski 11y ago

My molecular biologist friend's comment on this is pretty on-point, so I though it was worth sharing: This is one of the first gene therapy studies I've seen that didn't end with "but we accidentally gave our subjects aggressive leukemias, whoops". Extending telomeres is interesting! And there's a lot of good data that critically short telomeres can lead to and cause cellular senescence and death. But telomeres are just end-caps of entire chromosomes worth of DNA. They are interesting with regards to aging partly just because they are measurable and quantifiable, but aging is so much more complicated and multifactorial than just telomere length, that manipulating telomere length and saying this solves aging is an overstatement. Cancers can express telomerase and immortalize themselves just fine, for example. Manipulating telomeres to investigate aging reminds me of this classic joke. A cop pulls up late at night to a biologist slowly walking a spiral around a streetlight, staring at the ground intently. "Uh, sir," says the cop, "what are you doing?" "Looking for my keys," replies the biologist. "I dropped them somewhere on this street. "I see," says the cop. "But why are you just looking around this light?" "Light's better here", he replies.

joeyspn 11y ago
> My molecular biologist friend's comment on this [...] Manipulating telomeres to investigate aging reminds me of this classic joke [...] What's your friend speciality? Any link to his telomeres/telomerase papers, or any chance you can point him to Maria Blasco's [0] work (top researcher in the field with 200+ papers [1]) for comments?: It'd be interesting to see science-backed rebuttals. [0] https://en.wikipedia.org/wiki/Mar%C3%ADa_Blasco_Marhuenda https://en.wikipedia.org/wiki/Mar%C3%ADa_Blasco_Marhuenda [1] https://scholar.google.es/scholar?q=MA+blasco&hl=en&as_sdt=0 https://scholar.google.es/scholar?q=MA+blasco&hl=en&as_sdt=0

jstewartmobile 11y ago

It's Theranos all over again, with lower stakes.