For those who are interested in this topic, I'm just wondering what longevity research today looks most promising to you and why.  Whether that's SENS, cryonics, nanotech, brain uploading, etc is fine with me.  Any links to actual research papers would also be greatly appreciated.  I'm very interested in longevity, and am curious to see if anyone else would like to offer some thoughts on the current state of the art.

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Plastination. It has substantial plausibility and seems to be objectively testable (eg. ), and seems to be testable relatively soon with very small investments - so it is even more worth researching than it would initially seem because we can become certain quickly and either benefit quickly or move on to other strategies.

Is it wrong/biased to believe we should prioritize extending the longevity of our current bodies over "life extension" projects that can only work with brain emulation/simulation? It strikes me as far more likely to gain public support, or at least gain mainstream approval.

Plastination and brain scanning already has a great deal of mainstream approval, with large projects underway at mainstream places like Harvard, because the scientific benefits for neuroscience are so compelling & obvious.

Oh, did you mean support for the emulation part? Well, the nice thing about your brain being plastinated is that you can afford to wait a few decades/centuries in a way you can't if you're cryopreserved and organizational continuity is a serious problem.

Or did you mean expected value? I don't expect much from mainstream medicine since it has failed to extend old-age longevity much, and even if SENS or caloric restriction was surprisingly successful and extends life by a few decades, you still die in a few decades. Background reading:

Yes, that's basically my concern. I'm aware of the value of tissue preservation for other, "conventional" fields of medicine and science, but developing perfect preservation is just the first step in actually extending human lives. The second step - reanimation or emulation - strikes me as far more controversial and far more difficult as well. I understand the argument that we can postpone this step indefinitely once we've got preservation figured out, but, as I was saying, most people tend to think of their current bodies when they think "life extension".

I'm with you; of the items that christina originally listed, SENS is the really important one. Nonbiological nanodevices or nanoconstructs might be useful as delivery systems or probes, but mostly we should be interested in biology all the way, e.g. designer bacteria as "medical nanobots". Full-spectrum nanotechnology, and techniques for storing brain information, are really about opening the abyss of posthuman possibilities, and that's a severe challenge whose resolution ought to be intimately involved with however the human attempt at coexistence with artificial intelligence works out. But human rejuvenation is comparatively :-) straightforward and should be on everyone's to-do list.

Cryonics is still my favorite. Some reasons:

  1. They've vitrified a rabbit kidney. We know tissue can go through this and come out alive. A brain is just a few more steps.
  2. It preserves a lot of biological information in addition to dendrite connections. This information may or may not turn out irrelevant, but if it is relevant that could be a game-ender for plastination that would not be so bad for cryonicists.
  3. You can test for cellular viability and organ function as a way to see if what you try is working. With chemopreservation you are stuck with sterile microscope readings (and simulations based on them) as the only form of feedback. More forms of feedback is better.
  4. Unlike an anti-aging intervation, freezing the brain or kidney is something that can be tested in young animals with immediate results.
  5. Cryonics appears to be inexpensive if done on a significant scale. Even a few thousand patients at a time reduces costs considerably.
  6. Cryonics be used on people dying today. This applies to chemopreservation as well (if anyone gets around to offering the service), but not to anti-aging treatments.

The second most interesting to me is whole body replacement or "brain in a jar" technology. Since it would be a less complex system than the whole body and designed more according to human intuitions, I would expect such a system to be easier to maintain indefinitely than the body itself. The brain itself is a less complex system than the body as a whole, so neural aging seems like it should be less complex than whole-body aging.

It is also easier to perform cryonics on an isolated brain than a whole body, for physical and biological reasons. The exact concentrations of cryoprotectant can be fine-tuned to the brain, and the cooling rate is better for a detached head or brain than a body. Removing cryoprotectants and rewarming at the optimal rate should also be easier. Thus when it happens, it is reasonable to expect the first successful reanimations to be not of whole bodies but individual brains.

The interplay between microRNA induced pluripotency, transcriptome research, and regenerative medicine. The idea is that different states of the cell are characterized by different populations of RNA transcripts, and that by introducing RNAs appropriately, you can cause cellular de-differentiation.

Here is a list of compounds being tested by the National Institute on Aging (part of the NIH) to see if they will "prevent disease and extend lifespan in mice."

Oxaloacetate looks promising. (Lots of citations in the middle of the linked page.) It's also for sale here.

Citric acid directly metabolizes to oxaloacetate in the body. This guy is selling you fruit juice at $50 bucks an orange.

I asked BenaGene, a company that also sells Oxaloacetate, why, if citric acid directly metabolize to oxaloacetate, I should take its product rather than having a bit of lime juice every day. I received the following response:

Back when the "antioxidant" theory was big, there were several lifespan studies done with various antioxidants including Citric Acid (citrate) and ascorbic acid. There was no increase in lifespan.

While under certain conditions oxaloacetate can convert to citrate, and vice versa, it does not create the conditions we want. We want to flood the cellular system with oxaloacetate so that it converts to malate.

So why not just take a bunch of malate? (found in apples). It's because during the conversion of oxaloacetate to malate, NADH also converts to NAD+. This increase in the NAD+/NADH ratio is the key to activating AMPK which leads to similar genomic changes similar to a calorie restricted state. These changes then lead to increases in lifespan.

On the other hand, lime juice is very helpful for making margaritas.....

This is an interesting line of reasoning, which is not easily refuted. It seems quite plausible biochemically, and my strongest attack on it would probably be through the conjunction fallacy - while each of these steps seems reasonable, perhaps the entire chain is faulty.

However, there is one thing that seems blatantly out of place - and that's the scale of the process. The citric acid cycle as a whole operates at a catalytic concentration of 1-5 millimolar, in just about every cell of the body. Multiplied by 70 kg of weight per person, that would equal 70-350 millimoles, or roughly 10-50g of CAC intermediates in the body. If this pill is really hoping to dump enough oxaloacetate into the system in order to temporarily force the cycle to run backwards, a 100mg daily dose seems small. I would think you'd need at least 1g daily before it actually affects the citric acid cycle.

Do they teach science in school nowadays? I feel like the analysis that I'm doing should be doable by most scientifically literate people.

Resurrecting a long dead topic here. I have a BS in Chemistry and only learned about the citric acid cycle in my last semester as an undergrad. I doubt many physics, math or comp. sci. people are ever exposed to it so it may be that the analysis can be done fairly easily, but that most people don't have the prior information to flag this as improbable.

It's been 25 years since I took chemistry.

In what quantity? How much citric acid would you have to take to get 100 mg of Oxaloacetate? Plus, all supplements sold without a prescription in the U.S. have to naturally exist within the body or be in "normal" foods. If resveratrol had proved to have anti-aging properties buying it wouldn't be a ripoff even though resveratrol is in red wine.

47 grams per liter of lemon/lime juice. That converts to ~25 g oxaloacetate per liter. Oranges apparently have less citric acid, to the tune of perhaps 500mg oxaloacetate equivalent per liter of juice.

Food-grade citric acid (also sold under the name "sour salt", usually shelved with spices) is FDA-classified as GRAS. Looking at Amazon, the Spicy World Citric Acid in the 5-pound bag is $19.23 (free shipping for me, since I have Amazon Prime).

At the ~2g of citric acid metabolizing into ~1g of oxaloacetate you suggest, that translates to a price of $0.05 per three grams of oxaloacetate, or three orders of magnitude cheaper than buying a bottle of 30 100-mg capsules for $49.

Looks like the person peddling this stuff is basing it on mice studies.

There appears to have been clinical human trials which "show an average reduction in fasting glucose levels of 25% in Type I and Type II diabetics".

Didn't catch that, thanks. Might be worth a shot for people with elevated blood glucose (above 85mg/dl), very expensive though.

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