The transposon thesis is really interesting. If the problem is about those transposons, then aging might be more tractible then we currently assume.
With siRNA there’s an established way of silencing RNA that gets expressed in a cell. When it comes to retrotransposons you would create siRNA for every specific retrotransposon. For DNA transpopons you can create siRNA against Transposase.
From a research standpoint you would synthesie a chain of DNA that codes for siRNA for all the retrotransposons and transposase and CISPER it into mice. Then you wait and see whether the mice have extended lifespan. That’s relatively easy if you do it on the embryo level.
If it works with the mice it will be harder to do gene therapy on all the types of stem cells we have to nuke their siRNA but it’s a clear engineering challenge.
Modern DNA sequencing involves breaking the DNA into little pieces, sequencing those, then computationally reconstructing which pieces overlap with each other. That’s a lot more difficult when the pieces you’re interested in have millions of near-copies filling most of the genome. Also, the copy-events we’re interested in will vary from cell to cell.
While it’s true that most DNA sequencing is based on the approach of Sanger where you get a lot of short reads (~100 basepairs windows) and use the computer to puzzle them together, Long-Read Sequencing technology is emerging.
One interesting observation about transposons is that they were likely more plentiful millions of years ago given that our DNA is full with mutated transposons. If transposons are a major factor in aging across species then there’s evolutionary pressure as organisms have longer lifespan to reduce the transposon count. It would be very interesting to see whether active transposon count correlates with lifespan across different organisms.
Eric Weinstein argues that given that we chose to bread lab mice in a way that makes them get children at a younger age then wild mice there’s there are evolutionary forces that radically changed their telomere length.
If that mechanism holds we should expect that’s there’s also less evolutionary pressure to keep active transposon count in lab mice that we breed the standard way low and lab mice should have more active transposons then wild mice.
One interesting observation about transposons is that they were likely more plentiful millions of years ago given that our DNA is full with mutated transposons.
I don’t think this follows. Transposons are parasitic; they’re detrimental to their host. If our ancestors millions of years ago had many more active transposons than we do now, they would not have survived to reproduce.
The mutated transposons are better explained by occasional lapses of control in the germline that accumulated gradually over time.
The transposon thesis is really interesting. If the problem is about those transposons, then aging might be more tractible then we currently assume.
With siRNA there’s an established way of silencing RNA that gets expressed in a cell. When it comes to retrotransposons you would create siRNA for every specific retrotransposon. For DNA transpopons you can create siRNA against Transposase.
From a research standpoint you would synthesie a chain of DNA that codes for siRNA for all the retrotransposons and transposase and CISPER it into mice. Then you wait and see whether the mice have extended lifespan. That’s relatively easy if you do it on the embryo level.
If it works with the mice it will be harder to do gene therapy on all the types of stem cells we have to nuke their siRNA but it’s a clear engineering challenge.
While it’s true that most DNA sequencing is based on the approach of Sanger where you get a lot of short reads (~100 basepairs windows) and use the computer to puzzle them together, Long-Read Sequencing technology is emerging.
One interesting observation about transposons is that they were likely more plentiful millions of years ago given that our DNA is full with mutated transposons. If transposons are a major factor in aging across species then there’s evolutionary pressure as organisms have longer lifespan to reduce the transposon count. It would be very interesting to see whether active transposon count correlates with lifespan across different organisms.
Eric Weinstein argues that given that we chose to bread lab mice in a way that makes them get children at a younger age then wild mice there’s there are evolutionary forces that radically changed their telomere length.
If that mechanism holds we should expect that’s there’s also less evolutionary pressure to keep active transposon count in lab mice that we breed the standard way low and lab mice should have more active transposons then wild mice.
I don’t think this follows. Transposons are parasitic; they’re detrimental to their host. If our ancestors millions of years ago had many more active transposons than we do now, they would not have survived to reproduce.
The mutated transposons are better explained by occasional lapses of control in the germline that accumulated gradually over time.