Yes - IGF-1 is a well known target for life extension. It sounds like Loyal is just doing another version of Somavert, then coming out with a tablet version of the drug. See these discussions:
Here: Another (likely) Longevity Drug - Somavert / Pegvisomant
Totally. Just interesting in that it fits with that one more reason for why we may have to be careful with Peter Attia approaches to amounts of protein in our diets.
See also
There’s no evidence that (plant) protein intake is even associated with an increase in all-cause mortality in humans. While there are drugs being researched for IGF-1 reduction in animal models, it’s not even clear whether they will actually improve lifespan.
There is a ton of evidence on IGF-1 for longer lifespan and healthspan. Look into the research on Laron syndrome … people with very low growth hormone levels are tiny, but never get cancer and all live a long time…
Also - read this thread: Another (likely) Longevity Drug - Somavert / Pegvisomant
This is a very interesting case report, thanks for linking it. If it does pan out in larger dogs in the planned clinical trial, IGF-1 inhibitors can be considered the real deal. And just like with rapamycin, one should not take them until the age of 25.
Edit:
From a quoted study
Moreover, these IGHD individuals are partially protected from cancer and some of the common effects of aging and can attain extreme longevity, 103 years of age in one case. We think that low, but detectable, residual GH secretion combined with life-long reduction of circulating IGF-1 and with some tissue levels of IGF-1 and/or IGF-2 preserved may account for the normal longevity and apparent extension of healthspan in these individuals.
Longevity of these subjects with IGHD is apparently normal whereas various symptoms of aging are attenuated and/or delayed and healthspan seems to be extended in comparison with unaffected siblings
Growth Hormone Deficiency: Health and Longevity - PMC (nih.gov)
So lifespan is not extended but chances of developing cancer are significantly lower. It does appear that inhibiting IGF-1 only targets two causes of death (cancer and diabetes) but maybe the increased fraility leads to no changes on all-cause mortality?
You bring up a good point here. Many of us here who exercise a lot (including myself) probably have a bias towards exercise and strength training (and higher protein intake). We like feeling strong, and being very active and higher protein probably helps that.
But - the Laron Syndrome people seem to show that even extremely low levels of IGF1/growth hormone (which you would see with a low protein diet) don’t translate directly to extreme frailty. These people don’t seem extremely frail, though also don’t seem to be extremely strong / fit. But living in rural, mountainous Ecuador they do seem to get quite a bit of exercise.
But - in addition to not getting cancer or diabetes, they also don’t get Alzheimers. So, perhaps there is a bit of a trade-off here that needs to be recognized. And perhaps the risk of frailty from lower IGF-1/ protein is not as significant as some like to think?
Valter Longo suggests (in video below) that you get about 50% of the longevity benefits of lower IGF-1 when started later in life, compared to childhood, like in the Laron people.
Perhaps the best balance is pulsed IGF-1; mostly low, but occasionally high for recovery/healing/muscle growth?
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.
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.
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.
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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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
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.
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.
The current state of the Loyal effort from their company blog.
The source of their in-licensed drug candidate:
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.
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.
Good mainstream coverage by NYT and leading people like Eric Topol too
https://twitter.com/erictopol/status/1729961958122963125?s=46&t=zJMJ1xVdRJYEDYz-DHipTw
