PeterMcCluskey

PeterMcCluskey's Comments

Homeostasis and “Root Causes” in Aging

I wasn't trying to describe the root causes of aging. I was trying to distinguish between diseases that are avoidable via lifestyle changes, and age-related diseases that are sufficiently determined by our genes that we'll need major new technology to avoid them. The latter include things that impair our immune system and repair mechanisms.

My best guess is that the root causes of aging involve some clock-like processes that have been actively selected for different metabolism at different ages. See Josh Mitteldorf's writings if you want more on that topic.

Homeostasis and “Root Causes” in Aging

Alzheimer's, and several other age-related diseases, seem to be related to lifestyle, since they're rare enough in hunter-gatherer tribes that they can't be detected.

The kinds of age-related deaths that are common to all environments are mainly due to frailty, susceptibility to infectious diseases, and cancer.

Dec 2019 gwern.net newsletter

Gwern, thank you for your excellent coverage of hydrocephalus and the implications for intelligence.

The Thyroid Madness : Core Argument, Evidence, Probabilities and Predictions

I've had some large fluctuations in my thyroid levels, which have prompted me to develop a better understanding of thyroid problems than I had when this post was published.

I agree with a fair amount of this post, and I'm uncertain about a few of the claims it makes.

I agree that hypothyroidism is undertreated, and likely overlaps with CFS.

I think our prior should be that CFS has multiple causes, and that we shouldn't expect to find a single solution to all CFS. It's easy to find other conditions that have multiple causes. E.g. depression can be caused by hypothyroidism, hating your boss, Alzheimer's, etc. I expect that the less successful we've been at treating a syndrome, the more likely it is that it has multiple causes that we're poor at diagnosing.

So this seems plausible:

(2.1) CFS/FMS/Hypothyroidism are extremely similar diseases which are nevertheless differently caused.

I wouldn't even say that hypothyroidism is a single disease - it can clearly be caused by several unrelated underlying problems (too little iodine, too much iodine, autoimmune problems, etc).

I'm unclear on the extent to which conventional medicine disagrees with your position in claims 2.2, 3, and 4, or whether most of the disagreement is over the cost/benefit ratio of treating people who have normal TSH.

  1. TSH seems to be a pretty good measure of whether T4 levels need fixing. The main problem here is the confusion over what threshold to use to decide whether T4 levels are too low. I'm guessing there are two factors contributing to that confusion:
  • doctors are too eager to classify test results so that 95% of patients are considered normal, and to conclude that anything that's normal shouldn't be treated.
  • patients often have trouble detecting the problems associated with hypothyroidism. The symptoms are easy to confuse with aging, depression, etc, and treatment is typically designed to take effect slowly enough that improvements are subtle.

I felt a significant improvement in mood/energy/muscle comfort when I increased my T4 dosage to levels that dropped my TSH from 2.34 to 1.72. But I'm unsure whether I would have noticed, and connected the change to the thyroid levels, if I hadn't previously experienced some large, rapid changes in my thyroid levels.

OTOH, I definitely wasn't aware of the earlier changes associated with the initial rise in my TSH levels from 2.58 to 4.69, which I assume happened gradually over many months.

  1. I'm unclear whether many people deny the existence of problems with T3 levels. There's plenty of disagreement over related issues - maybe because suffering is hard to measure, maybe because of risks associated with T3 treatment, maybe because it's better to find and fix the underlying causes of the problem; I don't have a good idea what's going on here.

The AACB report of 2012 concluded that the normal range was so narrow that huge numbers of people with no symptoms would be outside it, and this range is not widely accepted for obvious reasons

He estimated its prevalence at 40% in the American population

I'm suspicious of these so-called "obvious reasons". I find it quite possible that nearly 40% of the U.S. population has mild to moderate problems due to low T4 (high TSH) levels. A TSH of 2.5 may be normal in the sense of being fairly common, but I consider it too high to be healthy. I think I would have described myself as having no thyroid symptoms during the first few years that I had what, in hindsight, were clearly moderate problems from hypothyroidism.

We also have evidence that, before iodized salt, thyroid problems were pervasive enough that people had little reason to think of them as abnormal. So it seems like we shouldn't assume away additional problems of this nature.

Such catastrophic failures of the body's central control system CANNOT be evolutionarily stable unless they are extremely rare or have compensating advantages.

I'm not too clear on how much of these effects qualify as "catastrophic failures". The widespread problems with low T4 and high TSH seem to qualify, and I suspect they're due to some moderately recent environmental (dietary?) changes.

The low T3 cases that I'm familiar seem like deliberate decisions that our body needs to conserve resources. Sometimes it looks like a reaction to calorie restriction or trauma, either of which imply that our body should prepare for a famine, or minimize the burden that a person places on the tribe when trauma impairs ones' ability to procure food.

It's unclear to me whether it's better to treat the low T3 levels, or to find and treat the underlying cause, but it seems pretty likely that doing one of those things is better than doing nothing.

Might humans not be the most intelligent animals?

My point is that the advantage to bigger brains existed long before humans.

This paper suggests that larger brains enable a more diverse diet.

Another AI Winter?

I think Robin implied at least a 50% chance, but I don't recall any clear statement to that effect.

Here is the Metaculus page for the prediction.

Should I floss?

After I started using a water pik, my dentist switched from recommending I return every 4 months, to every 6 months, without me telling the dentist that I was using the water pik.

I observe a clear difference in my gums, which appears to be due to the water pik, but I don't know whether it affects cavities.

Might humans not be the most intelligent animals?

The increase in human brain size seems more due to increased ability to get enough calories to fuel it than it does to the benefits of intelligence. See Suzana Herculano-Houzel's book The Human Advantage for evidence.

We run the Center for Applied Rationality, AMA

It's at least as important for CFAR to train people who end up at OpenAI, Deepmind, FHI, etc.

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