Dr Peter Attia on Rapamycin
Peter Attia is somebody I follow after seeing him in discussions with Dr Rhonda Patrick, both of whom are researchers in longevity. He switched from surgery to longevity and has practices in NYC and San Diego.
Anyhow he was on Joe Rogans podcast and talked at length about longevity and Rapaymycin, including dosages, what biomarkers to look at and side effects (including possible mouth sores). They talk about a number of things, but return to the Rapaymycin over the following half hour with lots of useful information. In here he talks about how he is getting set up to self experiment with this (he still has to get FDA approval for that kind of experiment).
Joe Rogan & Peter Attila starting at 1:06:16
My takeaway, Rapamycin is a "4 day fast in a pill" as he says. There are multiple effects to test for, one glucose resistance (which if is already good then you are unlikely to see an improvement), two immune function (which we have no clinical test for) and three immunoscence (again we have no clinical test for). He mentions that these are all three known benefits you get from a multi day fast. At any rate its only the glucose resistance you can easily measure.
Which makes me wonder what is being accomplished by doing the RAADfest announced blood panel, since (if true) it's only your glucose response that can be measured. Also, I'd put in another plug for multiday water only fasting as a sure fire experimentally verified modality to achieve the same effects and more. But you have to do the fast.
At any rate if you're taking or contemplating Rapamycin you should watch it. The rest of the podcast is talking about sports and such, but still with a longevity interest. For example around 1:45 he talks about how high performance sports actually eats away at longevity. Again getting to a post I wrote about balance in longevity - with some things like exercise, you don't want too little and you don't want too much. They talk about supplementation in general at around 1:54, and lifespan 2:13
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Interesting Dan. I followed Peter Attia for some time when I was interested in ketosis. This is the first time I've heard him talk about rapamycin.
There are some potentially undesired hormonal problems that can come with the caloric restriction of a 4-day fast (reduction of leptin and thyroid hormone T3, an increase in reverse T3, among others), that I suspect won't happen while taking rapamycin. So rapamycin may be a way to get the inhibition of mTOR and enhancement of autophagy without actually restricting calories.
There are some other factors relevant to rapamycin that are being assessed in the Age Management Panel besides glucoregulatory markers, with inflammation being one of them, and IGF-1 being another. Fasting reduces IGF-1, and it may be that rapamycin also reduces IGF-1 even if you continue eating, which some people suspect may be good for human longevity.
Then, inflammation reduction might reasonably be seen after taking rapamycin, in part because it it seems to be a senolytic, or may support the actions of senolytics. A reduction in the prevalence of senescent cells, which contribute to increased inflammation, might also reduce markers of inflammation, which are also in the Age Management Panel.
At this stage of research, it seems really important to me to measure many biomarkers as we self-experiment, because we don't know exactly what these compounds do or how they work in humans, and changes in biomarkers will help us understand these effects.-
Maximus I'm a measurement scientist by day so completely agree about the value of measurement. I do so with myself as much and as often as possible for health, so I'm not knocking the panel of tests at all, but it is worth noting that we're measuring secondary effects (inflammation, etc) and not the primary (senescence). Being a more informal study that makes sense.
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Dan Mc Hey Dan. That's terrific that you're so measurement-minded! Not many people are. When trying to tease out what works and what doesn't, paying special attention to measurement is very important.
That's an excellent point you make about not measuring senescence more specifically. We would like to do that, but the technical challenges are currently too much for us to include it in our panel.
For example, cellular senescence is often assessed in skin fibroblasts of the subjects. So we'd need for everyone to get a hole punched in their skin (skin biopsy) before and after an intervention, so we can perform a rigorous assessment of senescent cell prevalence. That assay is just too complicated for us at this point (partly because we don't have the staff, lab, or funds available to have this done).
By the way, some studies we are following do indeed assess senescent cell prevalence before and after the intervention. It's designed into the protocol and funded by donors, so the research team can afford to do this assessment for that particular study. -
Maximus Yeah my understanding is that measuring senescence is a lab not clinical test (usually involving killing your mice and fluorescing their cells IIRC). Thinking on it, I mentioned elsewhere that Dr Patrick has said that grey hair is caused by senescence cells, so perhaps informally it might be true that people would go less grey with treatment (or might not). Another that comes to mind is the Ames test which measures the amount of broken DNA excreted in your urine. I don't know if immunoscenscent therapy would increase, decrease or not effect the test, but it's an interesting thought experiment. On the one side I might think that you'd see an increase of broken DNA as your body flushes out the senescent cells. I also don't know how available that test is, but at least it's simple (urine sample) and perhaps not terribly expensive.
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Dan Mc Thanks Dan.
Yes, I'm familiar with at least one urine marker of DNA damage: 8'oxo-2-deoxyguanosine, abbreviated 8-oxo-dG.
I'm not sure whether that would be a useful marker for a study that we're interested in, in part because I understand it is confounded by changing rates of DNA damage and DNA repair. Maybe it would be. But as an example of confounding factors, I suppose a lot of sun exposure may increase urinary 8-oxo-dG, making it look like there is a lot of DNA damage being caused by the intervention, but it's actually just that a person went to the beach, or that it's summer out and the average urinary 8-oxo-dG will be seasonally higher. But I agree with you that in theory, it could have some relevance, as one reliable method of inducing senescence is DNA damage. I'll keep that marker under consideration as we contemplate various biomarkers to be used in our research.
I have listened to Dr. Patrick on a few occasions, and I'd be interested to hear her explanation of graying hair being caused by cellular senescence. I have never heard of that theory, though I haven't studied that topic in great detail. Maybe I've just missed it (there is so much to miss in the scientific literature if one is not looking for it specifically). -
Maximus the un-greying of hair as a marker of senescent cell removal has a precedent with the famous mouse experiment that started the 'zombie' senescent line of research. Where elderly mice regrew new young fur and lived longer with more energetic exploratory behavior after having their senescent lingering cells go to autophagy.
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I started listening to his podcasts frequently about a month ago.. Thanks for the heads up on this one.
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I don't think I saw the following mentioned yet in this thread. Dr Attia did 2 podcasts a month or 2 ago that were with some of the top rapa researchers. I found these interviews to be very interesting:
https://peterattiamd.com/davidsabatini/
https://peterattiamd.com/mattkaeberlein/
