What I'm saying is that it looks like there's an effect and that effect is visible as a change in expression vs length but that I wouldn't expect it to be too related to length in a meaningful way biologically. If you take one population of transcripts and another and you measure the lengths, it's likely that you'll see a shift in the median - regardless of whether length is important, particularly due to the specific ways in which length relates to sequencing depth. And on top of that, comparing across genes requires compensating in some way for the length of the gene and it's not obvious how to do that correctly - could they be finding an artifact of how they normalized for length? (Eg: a "gene" actually doesn't have a single length, it's multiple possible variations in transcripts of different lengths and most reads from the sequencer is ambiguous as to which it came from. Quantify the different transcripts incorrectly - and it's impossible to do it correctly - and you may be mis-estimating the effective length and mis-normalizing.) It's a starting point of an investigation, not an end point.

(And they do try to take the next step to make that investigation and they report that they see a further decrease in a gene related to transcribing long transcripts. However it's 27th in their list of related genes and I'm not sure how unlikely having one of the top N genes has a reported connection to transcription. Hopefully they will follow up with a biological experiment involving knock-down of this gene and seeing an accelerated aging phenotype or something of that sort.)

The most compelling piece of evidence in my mind here is that the effects they report are consistent in direction across conditions. The most worrisome is that they tested a bunch of factors and the only ones they report as consistently informative are the ones that confound technical aspects the most and therefore are confounded with any number of underlying biological changes.

I think it's actually a poorly worded sentence and it's saying that there's an anticorrelation between gene length and the relative expression levels between healthy people and those with ALS (and also between healthy people and those with Alzheimer's). This means that ALS and Alzheimer's both have similar effects as aging does and decrease expression of longer genes, according to their study. The sentence before it seems to be specifying the "anticorrelation" that they're talking about and the sentence in question is saying it holds in ALS and Alzheimer's as well as in aging.

Thanks AstralStorm!

There's such a thing as gene over-expression to artificially increase the number of transcripts of a gene expressed. It's generally less easy or reliable than gene under-expression where you interfere with the expression. Doing it to get all of the affected genes back to their "healthy" levels at once would be very challenging. There's about ~30,000 genes total and at one point the study was looking at the top and bottom 5% by length of those genes so you'd be looking to over-express 1500 genes - I've never heard of a study doing anything like that but it might be possible.

On top of that, there are also feedback loops so if you put more of a certain transcript in it may induce more/less of another or get the cell to stop production of that transcript and therefore counter-act what you've done. So it would be extremely hard to get to the desired levels in all of them.