All of William Walker's Comments + Replies

Look at how declining NAD+ levels in age shut down the cellular innate immunity system... it automatically kills off the old during epidemics.

And yes, this is another attempt by me to get you to pay attention to the recent developments in NAD+ boosting vs. coronavirus... there's finally a human trial on this in Denmark. Everyone please try to live long enough to worry about aging ;)

https://clinicaltrials.gov/ct2/history/NCT04407390?V_1=View#StudyPageTop

Those are all good points. One problem is that when the parasitic class prints itself a few trillion, it justifies it by also doing tax-supported "rescues" of obsolete companies, a terrible idea as your second paragraph implies.

You could say the same about WW2... and a lot of idiots have. Trillions of dollars worth of destruction (mostly from the "recovery programs", aka bailout opportunities grabbed by the upper-class twits) does not help anyone achieve any legitimate goals.

Those who talk about "less materialism" while supporting transfer programs from my barely solvent self to them can stuff it.

I'd accept the "practice for a more serious pandemic" one... that's true. Problem is that there is no sign of anyone working on stopping FDA and... (read more)

1bfinn
With the big exception of the reduced existential risk, I'm not claiming an overall net benefit. Though even existential risk aside, perhaps there is one (would need to do the calculations). E.g. it seems to me the long-term changes in work and work-life balance could be a huge permanent benefit; such as reductions in commuting and office usage, which seem a vast waste of time & money. It's a shame it takes a disaster like this to make it happen, but that seems to be the way the world works. The status quo has to be stretched to breaking point. Also not all the destruction is bad in itself - 'creative destruction' is a real thing. Some organisations really are just a waste of time & money, and are better off closed down so people & capital can find more productive use. Many were in a 'zombie' state before coronavirus. The UK department store chain Debenhams for example, which went bankrupt last month only a year after the previous time it had gone bust and been rescued. An outdated retail model for which there is no longer enough demand. I also know lots of classical musicians who barely scrape a living, and really there are too many chasing too little work. It can take decades for people to realise they're fighting a losing battle; a crisis can accelerate that.

(?) This is LessWrong... I thought everyone was either rich enough to sub to the big papers, or clever enough to get around the paywalls? If I had known that this club was going to accept me as a member, I shouldn't have joined!

Answer by William Walker20

Yes, I've been working from home since March, so have "ramped up physical training" in the sense that the borderline-personality collie demands that I run 20 miles per day now ;)

Although vaccines won't be available, there are other strategies available now that can reduce severity. One is NAD+ boosting, that ameliorates the single biggest defect in old cells, the downregulation of PARP10:

https://www.ispot.tv/ad/nq4g/tru-niagen-immense-energy

You girls all seem like normal nerds, what's the issue ;)

I get the "need equipment the right size" thing, our gun range keeps some short LOP stocks around for any women that wants to take up shooting.

BTW, I was told to learn to cook so I didn't starve to death... not sure that was actually some kind of gender abuse ;)

I did not know that... I can't spare many neurons, I'd better check it out.

2[anonymous]
To be clear, the work I am speaking of is on enhancing the NAD salvage pathway preventing NAD depletion in stressed neurons. This treatment seems to drastically decrease neuron programmed cell death in response to brain injury, neurodegenerative diseases, and hypoxia. The mose work showed great promise in brain injury and hypoxia and while it doesn't stop the neurodegeneration from ALS and the like (the underlying damage is being done) the threshold for individual neurons dying is raised, so the mice are healthy for a long time before suddenly falling apart rather than slowly declining. This is work being done by Calico and by Dr. McKnight. I will provide links when I'm no longer on my phone

The apoptosis pathway requires the mitochondria to be on... this has been noted since Warburg in 1935 (look up Warburg Effect).

More likely that NR would enable apoptosis to work correctly. Most of the time. Anything can happen with freakin' aneuploid cells, but that's how I would bet. Also, try to stop cells from going aneuploid in first place... this came up in the early days of telomerase research. Lengthening telomeres "sounds" like it would increase cancer, but it doesn't, if it's just from temporary activation (and I dun... (read more)

3[anonymous]
There is a whole bunch of work on boosting NAD levels to suppress PARP effects on NAD depletion triggering neuron apoptosis...

Thanks for clearing that up for me, I've read LessWrong for years but haven't tried to post much before the virus gave me some free time, I'm still getting used to the format.

You're right, you can overlap Phases if the FDA cooperates.

Answer by William Walker10

In 1957 they put together a flu vaccine in four months.


Of course, in 1969 we had flight-ready NERVA nuclear rocket engines. In 1962, Orion was ready for nuclear flight... progress doesn't always go in a straight line.

Least of all in biotech, where our incentives are so twisted that we use the most dangerous treatments first.

Moderna says they'll have their RNA vaccine in production by July, BTW. And there are safer treatments under study:

https://www.biorxiv.org/content/10.1101/2020.04.17.047480v1

Look up how much vitamin D you get from an hour of full-body sun exposure... if Vitamin D weakened defense against SARS-CoV-2 (instead of helping, as it does against other viruses), the Australians and Indians would have trouble ;)

...when actually they're doing much better than the US.

3philh
You're asking me to do a significant amount of work here, and it's not clear you understand the actual claims being made. "Vitamin D weakens defenses against SARS-CoV-2" is not a good summary of them. Edit: oh, to be fair that was somewhat my fault, apologies. I linked to the old version, and to a part of the page below where it says it's the old version. http://reasonableapproximation.net/2020/04/28/chris-masterjohn-on-coronavirus-part-2.html has more.

One thing we can do is eliminate inventory taxes... this is one reason that companies were forced into just-in-time. We currently punish people for being prepared for any emergency ;)

Sure, that's why he disclosed. (Although you're incorrect about "profitable", so far ;)

But the Sinclair lab at Harvard hates Brenner, Iowa, and apple pie, yet came to similar conclusions:

https://www.preprints.org/manuscript/202004.0548/v1

As far as lung health goes, tuberculosis prevalence is inversely correlated with B3 (of any kind, not just NR). This isn't some $@#! malaria drug or Ebola has-been, there's no side-effect downside.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3825668/

6ErickBall
Thank you, lots of good info in those links.

As someone who was immortalizing various cells with telomerase vectors in 2001 in the Shay-Wright lab, it's shocking to see the lack of study of telomerase activation. In 2020, you can either take Centella asiatica and astragalus like a Taoist monk, or you can use AAV-vector telomerase with no idea what it will do (it's probably not a great idea, since only rodents keep their telomerase on...)

Where are all the billionaires into cryonics that we see on Futurama (which is itself getting old...)

Answer by William Walker50

Agree with the Vitamin D, C, and zinc. Also take nicotinamide riboside (a B3 variant) to raise PARP10 levels. (Recent paper on this):

https://www.biorxiv.org/content/10.1101/2020.04.17.047480v2


And don't forget to stagger around the neighborhood biting everyone... millions of movie fans have been waiting for this for decades.

Is anyone using the short school day /two classes method? Given how the Finnish system works, it sounds promising.

Re susceptibility to SARS-CoV-2, I think this paper has a lot of the answer, especially for older people:

https://www.biorxiv.org/content/10.1101/2020.04.17.047480v2

5ErickBall
I would like to call attention to the conflict of interest statement at the end, where the senior author Charles Brenner is identified as chief scientific adviser of ChromaDex, maker of Tru Niagen, a profitable nicotinamide riboside supplement. I'm not saying the theory is necessarily wrong--NAD+ is implicated in many aspects of aging, and aging is obviously a risk factor for Covid mortality. But the effects of NR supplementation in humans have been a bit over-hyped in the past. Again, I don't mean to imply that it does nothing, but it has been pushed as an anti-aging supplement without good evidence for improvement of biomarkers other than NAD+. For instance this study found no effect on insulin sensitivity or other metabolic measures.

Agree that sending young people back first makes sense. Dr. Brenner's recent paper may explain why older people are at more risk, and how to fix the problem:

https://www.biorxiv.org/content/10.1101/2020.04.17.047480v2

LA Times article mentions the nicotinamide riboside/PARP10 connection from Brenner's paper. Taking NR is probably important and certainly safe.

https://www.latimes.com/california/story/2020-05-01/promises-covid-19-vaccine-therapeutics-cure

Except that in the real world, only regulations can enforce monopolies.... without force, there's no way to stop other firms entering and providing services for less.

The current "health care" in the US has the disadvantages of both top-down control systems AND the profit motive, of course.... so again, we already have top-down enforced monopoly.

http://www.strike-the-root.com/51/walker/walker6.html

You mine in space to build in space, mostly. But removing the ecological stress of deep mining, sea mining, and processing oxides instead of pure metals is not minor.

He-3 is certainly worth shipping back to Earth (for space nuts to use to fuel He-3 mining ships, obviously).

We've gotten too used to politically generated stagnation, with resources burned up in phony wars and competition for corporate welfare... people in 1910, with 6% economic growth rates, were a lot more able to understand that it was time to start thinking about Tsiolovsky's ideas.

I agree with CellBioGuy. Coincidentally I was a Cell Bio Guy... guess we were hardened by the Incubator Space Wars and their bitter aftermath ;)

Start with the truths applicable to biological aging, or you'll never get to the rest of them.

You forgot to check the old lady for a suicide belt before helping her across the street...

Ethics is more complicated than it looks. And it's way too complex and expensive to do much of it before you're independently wealthy. Get on your feet first.

Now we can launch into the "I could fix this in ten seconds if you'd stop lamenting it for ten seconds" discussion ;)

Never did understand why that Cimmerian would hang around listening to the lamenting for hour after hour... barbarians are strange.

NAD+ boosting (NR now, keep an eye on NRH for future).

CoQ10, NAC, keep D levels up in winter.

Telomerase activation (Centella asiatica, astragalus, eventually synthetics if Sierra Sciences gets its TRAP screen funded again or if the Chinese get tired of waiting on US technology...)

NR, C, D, Zinc for SARS-CoV-2 right now, if you're not already.

Become billionaire, move out of FDA zone, have some AAV-vector gene modifications... maybe some extra p53 copies, like the Pachyderms? Fund more work on Bowhead Whale comparative genetics. Fund a company to com... (read more)

I'd emphasize going back in logical order, e.g. people with positive antibody tests, under 30, that don't live with old people first, and so on.

A lot of Third World people are going to die from lack of food, medicine, and the rest of poverty, while we try to keep a few people in nursing homes "alive" for another month.

I'm FOR putting MUCH more effort into actually stopping SARS and the flu, but it has to be done effectively, not just as some new excuse for bailing out Freddie and Fannie..

Answer by William Walker00

Let's just save time by jumping to to the place where the AI in charge of AI Safety goes Foom and takes us back to the Stone Age "for safety" ;)

Answer by William Walker30

No. We should be re-assessing the idea of allowing the FDA to stop the Mayo Clinic, Co-Diagnostics, Roche, et al from producing PCR test kits during epidemics. Shutting down the Principle Of Comparative Advantage is not an option.

We should all personally re-assess our basement stockpiles, as well... going to the grocery to fight over toilet paper on the first day of the Zombie Apocalypse or some nuclear tiff, is not a reasonable plan. (My own stockpile had me on Planet Smug until I ran out of canned fruit... ;)