Thank you! Next step would be to determine optimal levels and modulation.
Just side note regarding that rapamycin seems to work better in elderly than fasting is something Mikail Blagosklonny points out in one of his papers.
“Notably, rapamycin more potently inhibits mTOR than does fasting, especially in old age”
Source: Fasting and rapamycin: diabetes versus benevolent glucose intolerance - PubMed
He refers to three papers regarding this.
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I’m very happy to see a discussion about this podcast. I listened to this episode and I found it so frustrating to see how much the need for patents is slowing down progress into this field.
It also seems that whatever is available won’t be available for aging straight away but rather “typical illnesses” which I just find frustrating!
I am sure when / if the new mTOR inhibitors are made available for a specific disease indications, that there will be doctors that will be willing to prescribe it off-label, just as rapamycin is. So it will be available. The bigger issue is how many people can afford the $10,000 to $20,000 per month that the medicine will likely cost if you are paying out of pocket for it.
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Reality, not many if any.
Members on this forum purchase overseas as the cost for generic rapamycin out of pocket is too high, a few dollars {less than a hundred]
How many on here would spend $4,000 a month out of pocket if it where available?
I think nobody on this forum.
Problem I have with this for profit model is that safety and efficacy is not the primary objective… money is… I think the incentive is in the wrong place. How can we trust that they are not gaming the system to get a defective drug approve because of… well… money…
Would not be the first time it happens… The entire research infrastructure is corrupt… my level of trust is low…
This is perhaps one of the key dilemmas in health research. Private investors will only invest if they think they might get more money back. However, governments are spectacularly bad at investing and it is best that don’t have a monopoly on investment. Where the balance lies is another issue.
When it comes to longevity private investors will invest if they think they personally may benefit. That is a helpful thing because it does create a limited amount of progress.
However, an underlying problem is the tendency (by the state or private investors) to fund research that they think has a good chance of coming up with a positive result. Hence the tendency to fund fads such as cellular reprogramming with the Yamanaka factors.
I am personally lucky in that like Bryan Johnson (but not to the same extent) I can invest in my own research where things like weekly blood tests have a material cost.
Oddly enough, like Bryan Johnson, I think I am making some progress, but only time will tell.
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A honest company such as “Pfizer”
Justice Department Announces Largest Health Care Fraud Settlement in Its History
Wednesday, September 2, 2009
Pfizer to Pay $2.3 Billion for Fraudulent Marketing
And they still made profit in 2009 after paying $2.3 billion.
Group orders of a synthesis and lab testing. In a Cyberpunk world where they would cost that much, most of us would have to go underground/black market for it.
Sounds interesting in theory, but has this ever actually been done? There are many expensive drugs out there, and many motivate sick people, but have you ever seen people actually doing a work-around like this to get access to a new drug? If it possible, you’d think someone have done it, and something would have been written about about it.
There has been plenty of group buys on Longecity, I’ve seen them over the years there. It’s all on the forum. A bunch of people get together and get a price quote from a chemist, buy the synthesis for ‘research purposes’, and then one person gets the order and ships it to everyone who bought shares.
These seem to be just for molecules / chemicals that are in early research and testing. Any examples with patented, newly discovered molecules that are commercial drugs, and people getting around the patent using this approach?
People there aren’t so patient. I don’t know about the case you’re mentioning, but if there ever is an interesting commercial drug I’d chip in to try a synthesis if others would be so as well. There’s probably a bunch of things that has to be researched and thought about. Longecity looks pretty dead though now and filled with spam.
I don’t have a good reference for this but older adults generally get less sensitive to both anabolic and catabolic stimuli. I recall a study on mice (can’t be bothered to look it up) that showed reduced autophagy activation at older ages compared to younger ages. I expect the same to occur in humans.
Can it be one of the below references that Mikhail is refering to in his paper where he states:
Notably, rapamycin more potently inhibits mTOR than does fasting, especially in old age
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No the study I had in mind was some human study. But anyways, these are interesting, thanks.
The third reference shows that pS-6 levels don’t decline as much in response to fasting in old compared to middle aged mice. See this quote from the full text and see Figure 1 B.
" As shown in Figure 1, fasting p-S6 levels were higher in old mice than in middle-aged mice. Noteworthy, fasting levels of p-S6 were lower compared with non-fasting levels in middle-aged mice (Fig. 1). However, we did not have sufficient material to compare fasting and non-fasting levels in old mice. Careful analysis of the literature allowed us to find missing data. In the paper by Sengupta et al,42 Figure 4 C shows that fasting strongly decreased levels of p-S6 in young mice, while only marginally affected levels of p-S6 in the old mice. This publication and our data complement each other."
This quote from the discussion section is also interesting and makes sense IMO:
“Noteworthy, physical exercise and IGF-I/nutrients cause mTOR-dependent increase of protein synthesis and muscle hypertrophy. In the aging muscle, this response is diminished.53,54 This may be caused by basal mTOR activity in aged mice,55 which precludes appropriate response to stimulation.53 Therefore, in order to prevent sarcopenia, one can consider an intermittent rapamycin treatment. This may decrease basal levels of mTOR activity (during rapamycin treatment), while allowing physical exercise and other physiological stimuli to induce mTOR (during rapamycin withdrawal). This prediction needs to be tested.”
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