> The research team discovered that the aging, senescent cells stopped producing a class of chemicals called nucleotides, which are the building blocks of DNA. When they took young cells and forced them to stop producing nucleotides, they became senescent, or aged.
^ From the article. Yet, when I check the linked journal entry:
> Inhibition of nucleotide synthesis promotes replicative senescence of human mammary epithelial cells
^ journal article title, which seems somewhat the reverse of the article claim.
> To test whether cellular immortalization would reverse these observations, we expressed telomerase in HMECs. In addition to preventing senescence, telomerase expression maintained metabolic flux from glucose into nucleotide synthesis pathways. Finally, we investigated whether inhibition of nucleotide synthesis in proliferating HMECs is sufficient to induce senescence.
^ From the journal article abstract. This states NONE of the "took young cells and..." claims from the article, but rather the opposite.
> Taken together, our results suggest that nucleotide synthesis inhibition plays a causative role in the establishment of replicative senescence in HMECs.
Umm...unless I'm missing something, this is literally taking correlation and determining causation.
TL;DR: This looks like an exploratory data point in the "how does the telomere clock actually cause senescence in a cell". While this COULD lead to some "new" treatment, vast issues remain, including both "is this the sole cause", "is this actually relevant", and "if this is the Big Cause, what could we do about it anyway?"
"Umm...unless I'm missing something, this is literally taking correlation and determining causation."
Yes. But when you're in a machine as complex as a cell and trying to figure out how to stop some process, if you can find a correlation, it's at least worth a try to treat that as causation. It's much better than picking a random answer.
Where we go wrong is when the game of telephone gets played and the correlation gets locked in as the official causation answer. But technically, "I see a correlation between A and B, therefore I hypothesize that the cause of the correlation is that A causes B" is at least a good first hypothesis. (The moreso when "B causes A" is not plausible for some reason.)
> if you can find a correlation, it's at least worth a try to treat that as causation. It's much better than picking a random answer.
No, it isn't. Or if it is, it's barely better, not much better. See my lengthier reply above.
The reason why this is false is because in biology, there is an enormous correlation structure in which, to a good approximation, everything is correlated with everything. If you take a random gene, its expression will be significantly correlated or anticorrelated with well over half of all other genes. Probably over 80% if I remember correctly. Depends on the number of samples, if you get into 10K+ samples it approaches 100%.
In an area like aging, skin wrinkling is correlated with sarcopenia is correlated with atherosclerosis is correlated with number of senescent cells is correlated with all kinds of gene and metabolite expression levels etc ... you get the idea.
In genetics a SNP will be correlated with hundreds of thousands of other SNPs.
I guess you can go so far as to say correlations can generate hypotheses. People certainly do this all the time. But "a correlation is tentative evidence of direct causation" is just wrong. Technically it is evidence, it's just that in my experience in biology it is such weak evidence as to be useless without other evidence.
"The reason why this is false is because in biology, there is an enormous correlation structure in which, to a good approximation, everything is correlated with everything."
Yes, but not all at the same ratios; it is not the case that literally everything is correlated to everything else to 99.9%. When people say "everything is correlated with everything" they mean that 60%s and 70% and 80%s show up in a large number of places, it does not literally mean that for every two possible processes the correlation is 99.9%. It's not practical to set up a large correlation net with that strong a correlation everywhere unless it really is all the same thing. (It might be mathematically possible, but it's not something you're going to encounter naturally.)
You're still better off choosing something that is very strongly correlated, because you have still shaved off huge swathes of the possibility space to start with which is much less likely to be directly involved. Yes, you still have a decent chance of being wrong, but you also have to remember that in the process of being wrong, you will gather more data. (Well... assuming that you actually listen to the data and don't hide behind some scientific dogma, but that's another discussion.) You're better off choosing something and probing than sitting there, agog at the net of correlations, and being paralyzed by the possibilities. Get in there and start shaving them off, and start with your best guesses, even if they're only your best guesses by a little bit.
All true - my complaint here was that the article went from "Here's a correlation that might indicate causation" to "This is the cause". Science journalism, I know, but still, if we don't call it out, will it ever improve?
I don't think the study was a bad thing at all (from my limited understanding), but the article was...a poor representation of it.
You're not wrong. But the point of the press release was not to convey understanding. It was likely a PR vehicle for the scientists and thus for the university. The ultimate goal is for all of them to make more money.
Paul Graham's essay "The Submarine" is quite instructive here.
> Finally, we investigated whether inhibition of nucleotide synthesis in proliferating HMECs is sufficient to induce senescence. In proliferating HMECs, both pharmacological and genetic inhibition of ribonucleotide reductase regulatory subunit M2 (RRM2), a rate-limiting enzyme in dNTP synthesis, induced premature senescence with concomitantly decreased metabolic flux from glucose into nucleotide synthesis.
This is the part where they took young cells and stopped them from producing nucleotides, and it's also what's described in the paper title.
^ From the article. Yet, when I check the linked journal entry:
> Inhibition of nucleotide synthesis promotes replicative senescence of human mammary epithelial cells
^ journal article title, which seems somewhat the reverse of the article claim.
> To test whether cellular immortalization would reverse these observations, we expressed telomerase in HMECs. In addition to preventing senescence, telomerase expression maintained metabolic flux from glucose into nucleotide synthesis pathways. Finally, we investigated whether inhibition of nucleotide synthesis in proliferating HMECs is sufficient to induce senescence.
^ From the journal article abstract. This states NONE of the "took young cells and..." claims from the article, but rather the opposite.
> Taken together, our results suggest that nucleotide synthesis inhibition plays a causative role in the establishment of replicative senescence in HMECs.
Umm...unless I'm missing something, this is literally taking correlation and determining causation.
TL;DR: This looks like an exploratory data point in the "how does the telomere clock actually cause senescence in a cell". While this COULD lead to some "new" treatment, vast issues remain, including both "is this the sole cause", "is this actually relevant", and "if this is the Big Cause, what could we do about it anyway?"