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Comment by pkilgore | Hacker News Reader

Now granted I only have a undergraduate degree in Chemistry, but to me, the statement "the lack of nucleotides causes cells to age" is akin to saying "the lack of steel causes a car factory to stop". Of course if a cell lacks the basic components to divide its DNA it... won't divide? The more interesting question is _why_ are there no nucleotides in cells that are aging.

My sense is that this summary of the underlying article is missing something (not uncommon in scientific journalism), or this really isn't all that revolutionary.

I'd love for a better explanation of why this matters, or a better link?

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I love your statement "the lack of steel causes a car factory to stop". You might not realize this but there is a lovely pair of articles comparing the approaches of genetics and biochemistry to understanding how car factories make cars. http://www2.biology.ualberta.ca/locke.hp/dougandbill.htm

The more biology you learn, the cleverer the jokes get:

"""Emboldened by his successes, the next morning the geneticist tied of the hands of an individual dressed in a suit and carrying a briefcase in one hand and a laser pointer in the other (he was a vice president). That evening the geneticist, and Doug (although he would not openly admit it), anxiously awaited to see the effect on the cars. They speculated that the effect might be so great as to prevent the production of the cars entirely. To their surprise, however, that afternoon the cars rolled off the assembly line with no discemible effect.

The two scientists conversed late into the evening about the implications of this result. The geneticist, always having had a dislike for men in suits, concluded that the vice president sat around drinking coffee all day (much like geneticists) and had no role in the production of the automobiles. Doug, however, held the view that there was more than one vice president so that if one was unable to perform, others could take over his duties."""

(in biology, many processes have redundant components)

This joke is only funny if it's taken as fact that authoritarian management hierarchies are necessary for industrial production. You take that notion for granted.

the joke leaves the role of the VP as undefined.

Fun link, thanks!

Of course a lack of steel causes the car factory to stop, but it would still be quite the discovery that car factories are regularly stopping because of a lack of steel.

In fact I wouldn't believe you if you told me that was in fact the case.

This is an exceptionally insightful point, thank you.

"... but it would still be quite the discovery that car factories are regularly stopping because of a lack of steel ..."

What if you dug deeper and found that the steel-lacking factories were the ones which made the worst cars ?

I think that's the default analogy you should be making when you see cells "stopping".

This idea that cells that stop processing, or that undergo apoptosis (cell death) or are incapacitated by free-radical damage / oxidation should be "saved" is probably a mistaken one.

It's probably a much better outcome that they die.

When you go off into analogies it can become difficult to determine whether the paralleled are insightful or worthless.

For what it’s worth though, I think there are plenty of examples of car factories closing down because they are unable to secure a supply of raw materials. The machinery and the workers are all still there, but for whatever reason the owner stops sending steel to the plant and it shuts down.

Make of that analogy what you will.

>>Of course if a cell lacks the basic components to divide its DNA it... won't divide?

The big thing here is that now they know that it is a lack of this particular substance causing the problem. Nobody could have guessed that this was the case. It is part of the debugging process. It provides a path for further discovery. Now they know where to focus their efforts.

Thanks for a great answer. I suppose it's rather quite like discovering a program isn't entering a code path. Knowing that is the first step to figuring out why it doesn't create a side effect at the end. (Metaphors all suck, but...yeah).

Here's the original article: https://viterbischool.usc.edu/news/2019/07/fighting-back-aga...

And the primary source/study: http://www.jbc.org/content/early/2019/05/28/jbc.RA118.005806

Thank you.

A better analogy is, you're given a broken car. The car barely runs. Why? You're also a caveman, you've never seen a car before.

No gas, that's why. How long will it take your cave man brain to figure that out?

Going into a PhD in genetics this fall. I think it's a good analogy, but it's more akin to say, "Factories that are closing don't have steel." To which, I think we'd all say, "Of course."

Don't we already have general knowledge about the molecular machinery that can stop cellular replication?

Wouldn't inhibiting nucleotide production already be explored well for cancer targets?

Isnt the only new thing here that they profiled and used senescent HMEC cells?

It seems they already had pharmaceutical and genetic means to target the protein already.

no steel => factory stops

does not imply

factory stops => no steel

Seeing that the factory has stopped, you need to determine whether it is because factory is lacking steel; or whether the effects of lack of steel consistent with current outage. This study seems to do this.

Excellent line of inquiry. I'll have to dig but I know I've read that senesence has an important function. Like most things in the body, it happens for a reason but there are often downsides.

It was probably something Dr. Judith Campesi, a pre eminent senesence scholar, wrote.

> I've read that senesence has an important function

Unless you're a water bear your DNA accrues continuous and irreversible damage throughout life. End of the road is either cancer or senesence as an attempt to arrest cancer.

Thank you. That was it. Senesence > cancer

Edit: Can't believe I forgot the third option, cell death.

Here's some info from Dr. Rhonda Patrick and Dr. Judith Campisi when they got together for an interview.

> As our cells accumulate damage, which naturally happens as we age (even as a consequence of energy-generating processes and immune cell activation), there are only so many outcomes that we can expect. The first possibility is that the cells can die. The second is that they can become senescent – where they stop dividing, but stay alive, all-the-while secreting molecules that influence surrounding tissue. Or, the worst of all possible outcomes, the cells can go off the rails and become malignant.

> "Anything that persistent damage to the genome will drive cells into senescence. It makes sense because that puts you at risk for mutations. Mutation puts you at risk for cancer, so the cells want to shut that damaged cell down." - Dr. Judith Campisi

https://www.foundmyfitness.com/episodes/59

Is it irreversible or simply at a greater rate than DNA repair? I thought there were DNA repair mechanisms.

It's irreversible because it's at a greater rate than DNA repair. At least, it is in mammalian non-germ cells.

Also, there isn't just one kind of DNA damage or DNA repair. Different kinds of damage have different orders of badness of effects and have different priors of happening by our cellular machinery.

It seems to me that they would now do studies to find out what increases or decreases nucleotide production in cells. If, for example, you found out that capsaicin in chilli peppers increased nucleotide production, then that could be useful.

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