#680

As I see it he is the sort of person that comes into the public domain and then over time leaves. I am not aware of any particularly new idea he or his team has come up with or any scientific discovery.

On the other hand he has not been doing me personally any harm or as far as I can tell anyone else on this forum.

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#681

I think you may have misunderstood . I’m saying you might be right after all since just about 100% of people on GLP’s see an increased rating heart rate despite profound health benefits.

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#682

If BJ’s negative assessment of rapamycin leads to fewer people taking the drug without adequate research and preparation, all the better. We don’t want people getting hurt. Plus, BJ seems pretty influential, so not having a massive run on rapamycin, means there’s less pressure on the supply for those of us using it :joy:.

But more seriously, we don’t need a bunch of unprepared followers sustaining health damage by jumping on a trendy drug. Rapamycin for the nerds, not the fashion followers, lol.

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#683

A fair point. In a similar vein Trump’s tariffs on Rapamycin will benefit rapamycin users outside the USA.

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#684

Obviously we agree on this. I did misunderstand your reply. My conclusion is that biomarkers need to be considered in the circumstances. This is harder but provides more reliable actionable information.

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#685

Pfizer will build the biggest rapamycin factories in the US! Bigly!

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#686

In a broader sense, however, the reduction in oil prices is likely to cause quite a problem for the USA. However, it is also likely to drive an increase in economic activity in the rest of the world. It depends how long it lasts. (it cannot last for ever)

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#687

Hence although I think it is arguable that a lower resting heart rate is an indicator of better heatlh, it is not necessarily the lower heart rate that causes better health downstream.

There are exceptions with things like blood pressure where a high blood pressure can be the cause of further damage.

The evidence for RHR causally impacting all-cause mortality isn’t strong anyways. The largest and most recent MR study found no association between RHR and ACM, suggesting the association found in a previous study was due to weak instrument bias. Elevated RHR did increase risk of dilated cardiomyopathy, but decreased risk of AFib and stroke. Source: Genetic insights into resting heart rate and its role in cardiovascular disease

It’s not like LDL-C and atherosclerosis where we have loads of evidence (RCTs+MR+mechanistic evidence).

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#688

"The LAM Foundation was made aware just yesterday by Pfizer that they will no longer sell or have availability of their brand drug, RAPAMUNE® in the United States, effective December 31, 2023. Please be assured that there are many manufacturers currently producing sirolimus, the generic form of RAPAMUNE®, to serve LAM patients.

Pfizer informed us they have decided that the availability of generics is sufficient to meet the demand for sirolimus in the U.S.

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#689

From Dr Fontana:

Caloric Restriction & Oxidative Stress:

Evidence from a 2-Year RCT Caloric restriction (CR) without malnutrition has long been associated with increased lifespan and reduced risk of chronic disease in animal models—but what about in humans? The CALERIE study, a landmark 2-year randomized controlled trial, offers compelling evidence that moderate CR (~13%) can significantly reduce systemic oxidative stress in healthy, non-obese adults.

https://lnkd.in/ggUE7DaW

Key findings:

  • A ~13% reduction in calorie intake led to a sustained decrease in urinary 2,3-dinor-iPF(2α)-III, a validated biomarker of lipid peroxidation and oxidative damage.

  • The CR group saw an 8-fold greater reduction at 12 months and a significant sustained reduction at 24 months, unlike the ad libitum group.

  • A composite isoprostane factor reflecting multiple oxidative stress markers confirmed a stronger and more consistent reduction in the CR group over time.

  • Changes in oxidative stress markers correlated with improvements in leptin levels and insulin sensitivity, suggesting interconnected metabolic benefits.

These findings offer the strongest human RCT data yet supporting the anti-aging and disease-preventing potential of CR—particularly through reduced oxidative damage. We’re just beginning to understand how dietary interventions can meaningfully impact aging biology. Exciting times ahead for translational geroscience!

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