Selection Has A Quality Ceiling

Nice point. I wanted to note that the converse is also true and seems like an example of Berkson's Paradox. If you only see individuals who passed the test, it will look like teachability is anti-correlated with the other two factors even though this may purely be a result of the selection process.

This may seem pedantic but the point I'm making is that it's equally important not to update in the other direction and assume less alignment between past experience and current skillset is better, since it may not be once you correct for this effect.

Daniel Kokotajlo's Shortform

This is basically a souped up version of TagTime (by the Beeminder folks) so you might be able to start with their implementation.

Core Pathways of Aging

Good point, this also suggests that Genome Project-Write is an important project.

Core Pathways of Aging

As a funny aside, a few months ago, I had the thought "removing all transposons would be a nice somewhat pointless but impressive demonstration of a civilization's synthetic biology mastery." I guess the "pointless" part may have been very wrong!

Core Pathways of Aging

As a thought experiment mostly for testing my own understanding, suppose we could do a bulk culling of transposons in all of an elderly human's stem cells (or all cells). If I understand correctly, this post's main hypothesis (DNA damage <-> ROS feedback loop) would imply the following should happen:

  • Senescent cell fraction quickly (within days or months) starts reverting to its healthy level.
  • Atherosclerosis heals on its own because ROS production reduces to its healthy level meaning the plaque equilibrium returns to the young level.
  • Similarly, vascular stiffening reverses for the same reason AG works temporarily.
  • Alzheimer's remains unclear without further understanding but we can guess this might help.
  • Sarcopenia same story as atherosclerosis and stiffening.
  • Lens and elastin fibers continue to build up, so we'll all be blind and wrinkly but otherwise healthy...

The one thing I'm less clear on is where immune system aging fits into this. I feel pretty confident that a treatment like this wouldn't cause the thymus to spontaneously grow for example but am more uncertain about some of the other aged immune system phenotypes. It seems plausible that reducing the load on the immune system would allow it to regain some of its ability to deal with infectious diseases for example.

Does this fit with your understanding?

Core Pathways of Aging

In principle, we could test it by looking for an age-related increase in transposon count in non-senescent cells, but that turns out to be actually-pretty-difficult in practice. (Modern DNA sequencing involves breaking the DNA into little pieces, sequencing those, then computationally reconstructing which pieces overlap with each other. That’s a lot more difficult when the pieces you’re interested in have millions of near-copies filling most of the genome. Also, the copy-events we’re interested in will vary from cell to cell.)

I wonder if something like single cell ATAC-seq could help here? There's still the problem of aligning near-copies but it seems like there's already some work trying to deal with this problem. (I haven't read either of these papers in detail but the second specifically mentions transposons as a use-case.)

Core Pathways of Aging

I've seen this claim about naked mole rats thrown around a bunch but it's left me with the question of what naked mole rats do die of? If their mortality likelihood truly doesn't increase, we'd expect there to be some very long-lived naked mole rats. Is the issue just we haven't held them in captivity for long enough to see them die of natural causes? I vaguely remember reading somewhere that eventually they stop eating or die in other ways but can't seem to find the reference now.

If you've learned from the best, you're doing it wrong

I agree that I'd want to learn physics from him, I'm just not sure he was an exceptional physicist. Good, but not Von Neuman. He says as much in his biographies (e.g. pointing out one of his big contributions came from randomly point to a valve on a schematic and getting people to think about the schematic).

(Disclaimer: not a physicist). From what I understand, Feynman was a really really good physicist. Besides winning a Nobel Prize for his work on quantum electrodynamics, he also contributed to several other areas during his career. Also, if you look at what other eminent mathematicians of the time say about him, you get the sense that he was exceptional even amongst the exceptional.

For example, Mark Kac, an eminent mathematician of the time, said:

There are two kinds of geniuses: the ‘ordinary’ and the ‘magicians.’ an ordinary genius is a fellow whom you and I would be just as good as, if we were only many times better. There is no mystery as to how his mind works. Once we understand what they’ve done, we feel certain that we, too, could have done it. It is different with the magicians... Feynman is a magician of the highest caliber.

Hans Bethe (another Nobel Prize winning physicist of the time) shared similar sentiments:

As the late, great Nobel Laureate physicist Hans Bethe remarked: "Feynman was a magician. With a magician, you just do not know how he does it."

I don't have the time to find more quotes like this right now but I think there are a bunch more like them if you look for them.

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