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Nov 2Liked by Max More

Nice article, thank you. However, something often missed in these discussions is to assess risks when you *already* do have specific diseases and you typically start doing when 60, 70 or 80. Take metformin for example which while generally antitumoral has some evidence of accelerating indirectly the growth of BRAF positive melanoma. Even Barzilai told me privately and informally once to exercise caution in these circumstances, maybe also for NMN. Felt literally on my skin(!)… BTW that would also imply your Plan B should become Plan A 😉 I look fwd to your coming book.

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Thank you. Your comment makes sense. Although being older should overall make it more sensible to take experimental treatments (those with substantial evidence), it definitely makes sense to consider known existing conditions. I had not heard that about metformin but I had heard that it could worsen/increase the likelihood of dementia. (I haven't looked into that enough to know how seriously to take it.)

If you are talking about cryonics/biostasis, that IS my plan A!

https://biostasis.substack.com/p/biostasis-longevity-plan-a

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Nice article here Max.

I think the timing is important. I especially would not want younger people to take life extension drugs if the potential, long term, side effects are unknown.

The calculus changes with older people, however.

Humanity has went through two main stages of “life extension.” The first raised average lifespans from about 35 to 70, mainly achieved by (cheaply) improving infant and child mortality.

The second wave came later, raising average lifespans from 70-80, but at great cost. This involves truly allowing people to live longer.

Those extra 10 years, however, are not spent in great health.

If a drug can be proven to make those 10 years more enjoyable and perhaps add a few more, it would be game changing. I see such a drug coming in my lifetime.

I added you on X, by the way.

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May I ask how old you are? That would give me an idea of your timeframe for expecting such a drug.

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He also says in his article "Either way, I would be taking a drug for decades without ever knowing that I was experiencing the benefits, while exposing myself to the possible harms."

Well, that's also the case with sport: in any case, you can play sports for decades, without knowing if it really had an impact on your longevity in the end, while exposing yourself to the possible risks of sport (injuries, accidents, and even risk of death).

Yet studies show that, generally speaking, it's better for our longevity to do sport than not to do it.

So why not apply the same reasoning to rapamycin?

I understand that its effects on humans are less proven than for sport, but I'm just reacting here to the fact that even for sport it's not possible to know definitively whether having done some makes you live to 88 rather than 80, so I don't think it is such a good argument to make.

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Food for thought Max (pun intended)

Being something of a contrarian, I tend to look at Life Extension (LE) from “avoiding an early death” point of view, the other end of the telescope, if you will. In that respect a newborn has the potential of living to say 125-years (our Hayflick limit) assuming we start with ideal genes and though our life manage to avoid any acceleration of our aging by an ideal diet, exercise, harm avoidance, pathogens and stressors etc, of course humanity still has an incomplete understanding of what represents ideal, which is why contradicting answers still abound in this space on what an ideal diet or exercise programme, for example, might be.

None of us live an ideal life and the majority of humanity who fail to die early start to prematurely pick up chronic diseases of mid life, which health conscious individuals attempt to mitigate with food supplement interventions and others that you list in your essay. I don’t think of an intervention as a “life extending” intervention but like a seat belt of a car, attempts at mitigating having a bad day. In that respect it’s not the gaining of 10% extra LE but not loosing what you already had in the first place.

As you point out, the risk-reward calculation of any intervention changes with remaining life expectancy.

Are we there with Rapamycin? The LE effects on standard small laboratory animals is encouraging, but cannot be considered definitive simply because the mechanisms of death tend to be different in even mice than humans. For a sixty plus year old the risk looks small for not loosing 10% years of life. However Rapamycin isn’t in any way a food supplement, not something found on Amazon or your local drug store, so not a practical intervention for most of us.

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