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.
(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.