Aging is associated with a systemic length-driven transcriptome imbalance
1–10 of 18 posts
Re: Aging is associated with a systemic length-driven transcriptome imbalance
#2My understanding of the text, is that there is a reduced expression in long genes (or locus) when people age.
Is this correct?
The text mentions an ALS gene (FUS) and contains this sentence which I have problem to understand (I am not an English native): Furthermore, we observe an anticorrelation among neurodegenerative disorders such as amyotrophic lateral sclerosis (ALS) and Alzheimer’s disease.
Please, what does those findings mean for Amyotrophic lateral sclerosis (ALS) and Alzheimer’s disease?
Re: Aging is associated with a systemic length-driven transcriptome imbalance
#3My understanding of the text, is that there is a reduced expression in long genes (or locus) when people age. Is this correct? The text mentions an ALS gene (FUS) and contains this sentence which I have problem to understand (I am not an English native): Furthermore, we observe an anticorrelation among neurodegenerative disorders such as amyotrophic lateral sclerosis (ALS) and Alzheimer’s disease. Please, what does t…
It means people with ALS don't get Alzheimer's according to a correlation. Now, how is the inherent lifetime and lifestyle difference bias corrected? No idea.
Re: Aging is associated with a systemic length-driven transcriptome imbalance
#4Yes, so longer genes are more likely to be impacted as expected given genomic damage theories and random damage model. (Likewise if transcription cellular machinery starts to introduce more random errors longer proteins would be impacted more.)
What to do about it? Edit whole genomes so they're more stable somehow? You cannot reasonably expect to remove all environmental insults.
Re: Aging is associated with a systemic length-driven transcriptome imbalance
#5My understanding of the text, is that there is a reduced expression in long genes (or locus) when people age. Is this correct? The text mentions an ALS gene (FUS) and contains this sentence which I have problem to understand (I am not an English native): Furthermore, we observe an anticorrelation among neurodegenerative disorders such as amyotrophic lateral sclerosis (ALS) and Alzheimer’s disease. Please, what does t…
It means people with ALS don't get Alzheimer's according to a correlation. Now, how is the inherent lifetime and lifestyle difference bias corrected? No idea.
Thanks AstralStorm!
Re: Aging is associated with a systemic length-driven transcriptome imbalance
#6A reason to take this with a grain of salt: transcript length is the biggest technical effect in RNA sequencing. Longer transcripts get broken into more fragments and get sequenced more deeply. What this means is that if you perform any experiment you tend to get a "length effect" of some sort. The second feature they mention in the GTEx data is GC-content, which is probably the second biggest technical bias in RNA sequencing and again basically any experiment has a "GC-content effect" of some sort. But I don't interpret those as meaning that there is something directly acting on long transcripts or high-GC transcripts, rather that whatever is happening biologically ends up appearing as a length or GC effect after sequencing. It's a little fishy that the only features they find are features that I would expect to always find.
The most compelling reason to think that's not simply the case here is that seem to be noticing a consistent downward trend across all long transcripts with age which is more compelling than merely noting that long transcripts change (some up and some down).
Re: Aging is associated with a systemic length-driven transcriptome imbalance
#7Yes, so longer genes are more likely to be impacted as expected given genomic damage theories and random damage model. (Likewise if transcription cellular machinery starts to introduce more random errors longer proteins would be impacted more.) What to do about it? Edit whole genomes so they're more stable somehow? You cannot reasonably expect to remove all environmental insults.
In theory couldn't we introduce fresh copies of longer genes via crispr or a similar process? How many long encoding genes are there?
Re: Aging is associated with a systemic length-driven transcriptome imbalance
#8Yes, so longer genes are more likely to be impacted as expected given genomic damage theories and random damage model. (Likewise if transcription cellular machinery starts to introduce more random errors longer proteins would be impacted more.) What to do about it? Edit whole genomes so they're more stable somehow? You cannot reasonably expect to remove all environmental insults.
In theory couldn't we introduce fresh copies of longer genes via crispr or a similar process? How many long encoding genes are there?
[deleted]
Re: Aging is associated with a systemic length-driven transcriptome imbalance
#9Yes, so longer genes are more likely to be impacted as expected given genomic damage theories and random damage model. (Likewise if transcription cellular machinery starts to introduce more random errors longer proteins would be impacted more.) What to do about it? Edit whole genomes so they're more stable somehow? You cannot reasonably expect to remove all environmental insults.
In theory couldn't we introduce fresh copies of longer genes via crispr or a similar process? How many long encoding genes are there?
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.
Re: Aging is associated with a systemic length-driven transcriptome imbalance
#10My understanding of the text, is that there is a reduced expression in long genes (or locus) when people age. Is this correct? The text mentions an ALS gene (FUS) and contains this sentence which I have problem to understand (I am not an English native): Furthermore, we observe an anticorrelation among neurodegenerative disorders such as amyotrophic lateral sclerosis (ALS) and Alzheimer’s disease. Please, what does t…
It means people with ALS don't get Alzheimer's according to a correlation. Now, how is the inherent lifetime and lifestyle difference bias corrected? No idea.
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.