Recent Debate Aubrey de Grey & Charles Brenner

I have now listened twice to this debate and it felt like eating cotton candy. What do you think?

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This was a pointed, entertaining, and informative debate on whether a longevity escape velocity can ever be achieved.

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Charles Brenner dismissed rapamycin as worthless too easily for my taste.

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Yes, he is extremely negative on pretty much everything except NR

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Brenner is only in it for money. Takes consultantes fees from Chromadax. Always hawking there products. In my mind Sinclair is in the same boat. de Grey, has sexual charges overhanging him and no one will will ask him to speak except for desperate. I personally was not impressed with him, but to his credit he has promoted longevity when there were very few around.

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Here are Brenner’s comments on rapamycin:

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For me, the essence of the debate was that de Grey maintained that there is a 50% chance of achieving longevity escape velocity within 15 years through breakthroughs that would repair damage, extending lives until the next breakthrough.

On the other hand, Brenner said that de Grey’s 7 Causes of Aging were not being tested for their falsifiability, there were no animal models to test them, and there were no technologies that had been shown to extend maximum life span. Therefore, there is a 99%+ chance that longevity escape velocity will not be achieved. Using the Wright Brothers analogy, de Gray responded, basically, the proof of the pudding will be in the tasting.

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I’ve been disappointed almost the whole time. I found it was a very limited debate: only what de Grey is trying or has tried, which is not the whole picture. And only in a critical (for Brenner) and defensive (for de Grey) attitude.

Not a word on this, for example: In vivo partial reprogramming alters age-associated molecular changes during physiological aging in mice | Nature Aging

And almost nothing on the basic theories of aging. That de Grey sticks with his accumulated damage theory is comprehensible, but Brenner then flips flops constantly: he is for repairing damages, that’s what he does, but he also insists that we have a genetic time limit (so the “programmed” theory). The latter would be good news, because such a genetic mechanism should be relatively easy to overcome with present technologies. But no, not a word, let’s jump back in this pool of almost petty criticism.

On the whole, I think that de Grey won the debate, at least on the sympathy meter, but I can’t shake the feeling that the momentum and maybe even the knowledge on the aging debate has lost ground here.

Some people now hope that there will be another such debate with Sinclair et Brenner. Frankly I hope not: I found that Brenner is much too negative to foster a fruitful debate. I see him already constantly bringing the mixed to poor results of resveratrol in humans trials as some sort of proof that aging research is at best a fad. And I would have to listen to this nevertheless :frowning:

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Interesting questions related to this debate:

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At 50 minutes Bremner infers that rapamycin causes muscle loss… I didn’t go further.

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de Grey’s longevity program is based on damage repair, and though this makes theoretical sense (the car repair analogy), Brenner is right that there has been little progress on this front, and no proven repair therapy that extends life. I also suspect de Grey’s estimate of 50% of LEV in 15 years is far too optimistic, though of course I hope I’m wrong.

Is there a thread that discusses progress in repair therapies?

For now, we have rapamycin to slow aging, and the usual ways to increase healthspan.

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LEV doesn’t need that much of an achievement: it is enough to gain one year of health/lifespan in one year of R&D. But the definitive proof would take decades to gather, at least. A proof with model organisms would not be accepted as such. So I don’t know what de Grey really means with this. But he can point to progress in several domains, and it sure is a very good thing that this research is done. So thank you Mr. de Grey!
He gave a brief about that here (sept. 2021:

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The thing with repair pharmaceuticals or supplements or even other lifestyle factors related to damage repair on a micro level is that they have to all be done together to really see the effects, but they have a special potential for robust anti-aging.

People may wonder why single target things like rapamycin work so well alone. Its because its mainly reducing the burn rate by bottlenecking the mtor pathway. This slows all forms of damage without directly repairing.

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Albeit it looks like cocktails with rapamycin also are promising:

The latest study with rapamycin:

https://www.nature.com/articles/s41598-022-11229-1

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Scientists have shown that a combination of rapamycin, acarbose, and phenylbutyrate has a synergetic rejuvenation effect when administered to 20-month-old mice for three months

Doesn’t it seem as if rapamycin with a ketogenic diet would produce similar results? Acarbose blocks starch digestion, and that starch might then be consumed by the gut microbiome or simply expelled. This is similar to a ketogenic diet, particularly one that includes fiber or resistant starch. Phenylbutyrate acts as an inhibitor of histone deacetylase (HDAC). Beta Hydroxybutyrate, a common ketone produced by the ketogenic diet, also acts as an endogenous inhibitor of HDAC.

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