timsbq
#1
I have just seen the following YouTube video which suggests that Rapamycin might be bad for the heart:
The description for the video has the following link to a scientific paper:
Rapamycin is known to be effective in suppressing senescence and the senescence-associated secretory phenotype (SASP). Therefore, it is highly expected to represent an anti-aging drug. Its anti-aging effect has been demonstrated at the mouse individual level. However, there are not many clinical findings with respect to its activity in humans. Here, we aimed to clarify the effect of rapamycin on human endothelial cells (ECs) as an in vitro model of human blood vessels.
In humans, the clinical applications of rapamycin including the elution with rapamycin stent have shown many adverse side effects such as stomatitis, myocardial infarction, heart failure, and hypotension. Although reports of side effects to blood vessels are not well known, adequate caution is required for the clinical application of rapamycin. From the results of our study, we propose that rapamycin should be used in combination with an early-stage autophagy inhibitor, which is not involved in lysosome inhibition, and that other SASP inhibitors need to be developed to prevent aging-related vascular diseases.
Does anyone here know what to make of this?
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jakexb
#2
This is interesting and a little concerning. This paragraph seems to be the key for me:
The beneficial effects of rapamycin on the vascular system have been demonstrated at the mouse individual level. In mice fed a high-fat diet, which is accompanied by increased vascular senescence and vascular dysfunction, rapamycin prevents vascular senescence and reduces the severity of limb necrosis and ischemic stroke [60]. Lesniewski et al. [61] showed that dietary rapamycin treatment improves age-related vascular dysfunction including endothelium-dependent dilation and increases the aortic pulse-wave velocity in aged mice. In these reports, the relationship with autophagy is unknown. To date, many preclinical studies on the relationship between autophagy and cardiovascular diseases have been performed [62, 63]. From those studies, it has been suggested that autophagy plays a dual role in cardiovascular disease progression, acting in either beneficial or maladaptive ways, depending on the context. In this study, we showed that the activation of autophagy contributes to the promotion of EndMT. It is known that EndMT is involved in cardiovascular diseases including atherosclerosis, pulmonary hypertension, valvular disease, and fibroelastosis [41, 42, 50]. Therefore, in cardiovascular tissue, whereas the positive effect of rapamycin has been shown, there is also a possibility that the activation of autophagy by rapamycin might be detrimental with respect to EndMT-related pathologies involving atherosclerosis.
Under some conditions, it appears rapamycin is quite beneficial. But it appears once there are certain diseases such as āatherosclerosis, pulmonary hypertension, valvular disease, and fibroelastosisā it is possible for rapamycin to actually worsen the diease. Possibly in that the senescent cells, while generally undesirable, are better than what they would be replaced with by the body should autophagy clear them out.
Not really sure what the takeaway should be here.
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Autophagy follows a U shaped risk curve like mostly everything else. Since rapamycin has so far universally lead to longevity, it probably hits the sweet spot.
Supplementing it with other autophagy inducers May be excessive and risky.
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Hereās a good summary of the pros and cons of autophagy.
For instance, Iāve stopped curcumin since starting rapamycin 51/2 years ago.
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Is there any way to tell if you are inducing too much autophagy?
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jakexb
#6
That makes sense. What are your thoughts about certain cardiovascular conditions where autophagy might be a net negative? Possibly situations where since cardiac cells donāt regenerate very readily, killing off senescent cells might not be a great move?
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Wouldnāt this have become apparent in transplant patients as they are dosing daily?
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Thereās no biomarker that would be clinically practical.
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Even removal of senescent cells is tricky as theyāre necessary for wound healing and probably play a significant role in cancer prevention.
Human biology is Extremely complex and we generally donāt understand what weāre doing. I try to avoid any shotgun approach.
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jakexb
#10
Thatās a good point. Actually hereās a study specifically about long term rapa use in heart transplants:
Early conversion to SRL (sirolimus) is associated with attenuated CAV (cardiovascular) progression and with lower long-term mortality and fewer CAV-related events compared with continued CNI (calcineurin inhibitor) use.
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So this would infer that Rapamycin is a benefit for the cardiovascular system overall?
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I have atherosclerosis. I take a supplement called Endocalyx which, in studies, has shown to improve the glycocalyx, the micro thin gel layer that lines the inside of all blood vessels which contributes to healthy endothelial cell function. Hopefully this will protect against any Potential negative effect of the Rapa
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FWIWā¦
Review this posting from July, 2022
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well I donāt know what to make of thisā¦i had a stent put in my heart for blockage on January 4ā¦the stent itself is rapa elutingā¦I am also taking rapa and donāt want to make my heart worseā¦a lot of different research pointing in different directionsā¦indeed human biology is a complex thingā¦I may explore Endocalyx which @Pestodude was suggesting
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what is your current rap usageā¦i had a stent put in my heart because i had 80% blockage of my LAD artery but rest of arteries were much betterā¦how did you atherosclerosis present? I am on 10 mg rapa weeklyā¦and statins, ezetemibe and PCSK9 inhibitors to reduce cholesterol.
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Years ago I had my lipids tested and had they werenāt crazy high but my doctor wanted to me to get a CAC test. It came back with a calcium score of 160. He put me on 10mg of Crestor. Had it tested again a couple years ago and it was up to 460 so Iāve been really trying to do whatever I can to slow it down. I have no symptoms.
Iām currently taking 6mg of Rapa every two weeks with fresh squeezed white GFJ so maybe thatās the equivalent of 20 mgs every two weeks.
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Agetron
#17
Although some say nothing can undo the damage of atherosclerosisā¦ some say nothing can reverse organ damage and agingā¦ we know thatās wrong.
Rapamycin might not just stop further damage but undo the damage. For me after 2 years of rapamycin my Coronary Calcium Scan is zero and I eat a lot red meat, whole milk and snacky foodā¦ low on veggies and fruits.
I donāt have a baselineā¦ so not sure why my score is perfectā¦ heart of a person under 35 years-old. I know my veins opened up due to Rapamycinā¦ veined out all the timeā¦ kinks and varicose veins gone. So its changing my blood.
Hope you get a good reportā¦ do let us know if your CAC score goes down.
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I remember years ago that Dean Ornish was a popular guru when it came to reversing heart disease. What ever came of that? I havenāt followed it - but wonder if other books / programs are more well-researched and validated now? Any medical professionals or cardiologists care to weight in?
https://www.ornish.com/undo-it/
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Its about facilitating the expression of long genes
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well, i donāt know what to make of it. the video is pretty sketchy on any details.
Iāve heard Matt K. on a video with Peter A. say that we have no idea how autophagy really works to any degree. And people who say they undertand it are lieing. And that Rapa doesnāt do much of anything in terms of autophagy - it primarily quiets the SASP and generally tells the cell to stop growing and hunker down.
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