I fully agree, a cyclical approach may be in order. If you train during the week, taking a IGF-1 inhibitor with a short half life during the weekend could be a good approach.
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Just wanted to note, Rapamycin, which inhibits mTOR, also inhibits IGF-1 further down the pathway. So you get both with rapamycin.
This is why you see that the animals that are dosed rapamycin early in life are smaller than otherwise (and they probably have other developmental problems so you’d never want to use rapamycin on any young mammals)… But the point here is that its not clear to me that, in adults, you’d get additional benefit with both rapamycin and an IGF-1 inhibitor.
And, more importantly, if we’re taking rapamycin we’re probably already getting a significant amount of the benefit of IGF-1 reduction, and the longevity benefits that flow from it.
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AnUser
#11
Frailty and decrease in muscle mass is so “easy” to detect and reverse, while aging is hard to detect and hard to reverse. If there is side effects from decreasing IGF-1 like that, it can be stopped.
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Neo
#12
Seems like this makes the tracking of IGF-1 (and perhaps related markers?) extra important as part of the core rapa blood work battery!
(eg before and after start over time and also when changing dose size, interval, etc).
Does anyone have blood work on how IGF-1 changed (or did not change) pre vs post rapa or change in rapa dosing?
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jakexb
#14
Meanwhile in humans, it seems growth hormone, at least done in a certain way, can reverse epigenetic age:
Its interesting… there is some significant disagreement about the TRIIM-X trial interpretation (and previous trial) in terms of what the epigenetic changes actually mean. Eric Verdin of the Buck institute thinks that the change actually just could be a change in the distribution of the type of cell being measured in the epigenetic test - so there was no actual rejuvenation.
See the full video of the presentation here if you want to understand this: The Longevity Drugs Pipeline and Biomarkers of Aging
Neo
#16
Think that it was the thymus generation that could help reverse aspects of aging “despite” the growth hormone, not necessarily the short duration of growth hormone itself.
Davin8r
#17
For sure. Peter Attia is really pushing the protein/resistance training angle these days, with the correct idea that it will reduce frailty in older age. I suspect, however, that it comes at a trade-off of speeding up the underlying aging process itself. It requires some nuanced thinking to understand that both can be true. The crucial question to me is still how much extra real-world muscle am I gaining/holding onto, with resistance training constant but high vs moderate vs lower protein intake? I know it makes a difference, but how much real-world difference? For instance, IF I could still get 90-95% of the benefits of resistance training with lower protein intake (while replacing those calories with healthy carbs/fats), it doesn’t seem worth the trade off. Or perhaps cycling high-protein with low-protein phases, or full fasting, or fasting-mimicking phases might provide similar muscle benefits without the downsides.
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The current state of the Loyal effort from their company blog.
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The source of their in-licensed drug candidate:
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Absolutely. Peter Attia is currently emphasizing the protein/resistance training approach, rightly emphasizing its potential to reduce frailty in older age. However, my suspicion is that this approach may come with a trade-off of accelerating the underlying aging process itself. It requires nuanced thinking to recognize that both perspectives can hold true. The key question, in my opinion, is still related to the tangible real-world impact on muscle gain and retention, keeping resistance training constant while varying protein intake between high, moderate, and low levels. While I acknowledge that protein intake does make a difference, the critical consideration is how much practical difference it makes. For instance, if I could achieve 90-95% of the benefits of resistance training with a lower protein intake (while replacing those calories with healthy carbs/fats), the trade-off may not seem worthwhile. Alternatively, exploring cycles of high-protein and low-protein phases, or incorporating full fasting or fasting-mimicking phases, might offer comparable muscle benefits without the associated downsides.
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Bicep
#22
I couldn’t help it, when I saw this at first it looked like the dog was announcing his partnership with Crinetics. Good dog. Smart dog.
Neo
#23
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Beth
#24
My VERY uneducated guess has been that he is probably fine consuming high levels of protein because he is on rapamycin. I have wondered if he would still do it to the same level if he weren’t, and if he wasn’t fasting to make up for effects he’s not getting on rapamycin. No idea but this is what has occurred to me…
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Neo
#25
And
Read here:
Full (unpaywalled) story: https://archive.ph/U3EQY
From:
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Davin8r
#26
[johney12] is some kind of bot, right? He/it has just been regurgitating my posts with slightly different wording.
AnUser
#27
Yes it is a GPT bot, I’ve told it to RapAdmin.
We should leave it be and see what it does, unless it will post a lot until revealing its hand and true purpose…
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This bit of humor as we start getting long-lived pets…
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This makes me wonder if anyone has seen a study showing IGF-1 levels before and after rapamycin? In theory, rapamycin might reduce IGF-1 levels because it influences it indirectly, but I’m not sure the effect amounts to anything significant at normal oral intakes.
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