8 ms·

tldr for biologists out there. They made a transgenic mouse line of doxycycline inducible Yamanaka factors in progeria (LAKI) background. Too high induction lea

by daemonk 10y ago

tldr for biologists out there. They made a transgenic mouse line of doxycycline inducible Yamanaka factors in progeria (LAKI) background. Too high induction lead to mortality and teratomas, which is known. They cyclicly induced the Yamanaka factors and found it reversed signs of aging (prolong lifespan by ~30%)

leereeves 10y ago
They didn't test this (or haven't yet) against normal aging in mice, only mice with progeria (unusually rapid aging)?
- deleted 10y ago
  [deleted]
JohnJamesRambo 10y ago
Why did they use the mice with the progeria gene? Wouldn't the results be more impressive in wild-type mice? Were they just trying to get around the 2-3 year lifespan of a lab mouse faster?
- lvs 10y ago
  Oh they did, in fact, but the results in WT mice were not as easy to overhype. The effects were extremely minor to nonexistent in aged wild-type animals (Fig S7 from the paper). Unfortunately, press releases and the subsequent news articles -- as usual -- have totally oversold what this paper means.
  - deleted 10y ago
    [deleted]
  - RushAndAPush 10y ago
    So what you're saying is that the mice that didn't have their genome edited didn't have a drastic life extension? I assume the improvements only occurred in the mice that had their genomes edited to reduce Yamanaka factors because they then artificially replaced the Yamanaka factors?
    - lvs 10y ago
      No. That's not quite what I'm saying. There was no particularly interesting effect of inducing transient expression of the Yamanaka factors on normal mice reported in this paper. It is effectively a negative result that's being reported, as it pertains to wild-type mice. The paper primarily reports results that pertain to mice with a genetic defect that causes progeria. Mice with this defect have a shorter-than-normal lifespan.
      - return0 10y ago
        so its more a treatment for progeria than general aging reversal
- sparky_ 10y ago
  I had the same thought. This puts an asterisk on the integrity of the report IMHO. Doxycycline has also been shown to greatly increase life expectancy! Of patients currently suffering from bacterial infection.
  - tominous 10y ago
    Yes and tetracyclines like doxycycline affect mitochondrial function and may confound the research in that way too. http://dx.doi.org/10.1016/j.celrep.2015.02.034 http://dx.doi.org/10.1016/j.celrep.2015.02.034
anigbrowl 10y ago
Thanks so much. I don't know why news headline writers are so insistent on bullshit, when they could have taken a cue from you and said 'gene therapy increases mouse lifespans by 30%,' which would have been just as short and interesting but vastly more honest.
- tn13 10y ago
  But very bad clickbait. The problems of media relying to eyeballs and ad clicks :)
  - srcreigh 10y ago
    Clickbait title to support the media business (marketing, journalist salaries), Hacker News for the summary.
- lvs 10y ago
  Not quite. The actual article title is far more correct than either the clickbait headline or your headline: "In Vivo Amelioration of Age-Associated Hallmarks of Progeria by Partial Reprogramming" (my addition)
  - bjelkeman-again 10y ago
    But that is really hard to understand for a non-specialist. Means nothing at all for me.
    - lvs 10y ago
      Well, I'm quite sorry to hear that, but the paper was written for specialists, and its results are primarily interpretable by and relevant to specialists. Why exactly it made it into a press release and news articles is completely inexplicable when analyzed within the bounds of the work.
      - ptero 10y ago
        A popular science, or even general news type reviews of current research are very valuable. However, in the unavoidable simplifications, they do need to keep the main findings correct, not expand into outlandish claims for clickbait
taneq 10y ago
Pop-science-journalism headline is predictably overblown... I guess "scientists reduce impact of progeria in mice" doesn't have the same ring to it.
yread 10y ago
So they had mice with a disease that caused early aging and managed to fix that. But there was almost no effect on mice who do not have this disease. Makes me wonder how overhyped this whole "our children will live for hundreds of years" thing really is.

by daemonk 10y ago

leereeves 10y ago

They didn't test this (or haven't yet) against normal aging in mice, only mice with progeria (unusually rapid aging)?

deleted 10y ago
[deleted]

JohnJamesRambo 10y ago

Why did they use the mice with the progeria gene? Wouldn't the results be more impressive in wild-type mice? Were they just trying to get around the 2-3 year lifespan of a lab mouse faster?

lvs 10y ago
Oh they did, in fact, but the results in WT mice were not as easy to overhype. The effects were extremely minor to nonexistent in aged wild-type animals (Fig S7 from the paper). Unfortunately, press releases and the subsequent news articles -- as usual -- have totally oversold what this paper means.
- deleted 10y ago
  [deleted]
- RushAndAPush 10y ago
  So what you're saying is that the mice that didn't have their genome edited didn't have a drastic life extension? I assume the improvements only occurred in the mice that had their genomes edited to reduce Yamanaka factors because they then artificially replaced the Yamanaka factors?
  - lvs 10y ago
    No. That's not quite what I'm saying. There was no particularly interesting effect of inducing transient expression of the Yamanaka factors on normal mice reported in this paper. It is effectively a negative result that's being reported, as it pertains to wild-type mice. The paper primarily reports results that pertain to mice with a genetic defect that causes progeria. Mice with this defect have a shorter-than-normal lifespan.
    - return0 10y ago
      so its more a treatment for progeria than general aging reversal
sparky_ 10y ago
I had the same thought. This puts an asterisk on the integrity of the report IMHO. Doxycycline has also been shown to greatly increase life expectancy! Of patients currently suffering from bacterial infection.
- tominous 10y ago
  Yes and tetracyclines like doxycycline affect mitochondrial function and may confound the research in that way too. http://dx.doi.org/10.1016/j.celrep.2015.02.034 http://dx.doi.org/10.1016/j.celrep.2015.02.034

anigbrowl 10y ago

Thanks so much. I don't know why news headline writers are so insistent on bullshit, when they could have taken a cue from you and said 'gene therapy increases mouse lifespans by 30%,' which would have been just as short and interesting but vastly more honest.

tn13 10y ago
But very bad clickbait. The problems of media relying to eyeballs and ad clicks :)
- srcreigh 10y ago
  Clickbait title to support the media business (marketing, journalist salaries), Hacker News for the summary.
lvs 10y ago
Not quite. The actual article title is far more correct than either the clickbait headline or your headline: "In Vivo Amelioration of Age-Associated Hallmarks of Progeria by Partial Reprogramming" (my addition)
- bjelkeman-again 10y ago
  But that is really hard to understand for a non-specialist. Means nothing at all for me.
  - lvs 10y ago
    Well, I'm quite sorry to hear that, but the paper was written for specialists, and its results are primarily interpretable by and relevant to specialists. Why exactly it made it into a press release and news articles is completely inexplicable when analyzed within the bounds of the work.
    - ptero 10y ago
      A popular science, or even general news type reviews of current research are very valuable. However, in the unavoidable simplifications, they do need to keep the main findings correct, not expand into outlandish claims for clickbait

taneq 10y ago

Pop-science-journalism headline is predictably overblown... I guess "scientists reduce impact of progeria in mice" doesn't have the same ring to it.

yread 10y ago

So they had mice with a disease that caused early aging and managed to fix that. But there was almost no effect on mice who do not have this disease. Makes me wonder how overhyped this whole "our children will live for hundreds of years" thing really is.