#240

Thanks for sharing, very interesting study.

"Our findings show that the diversity of blood stem cells is lost in older age due to positive selection of faster growing clones with driver mutations. These clones ‘outcompete’ the slower growing ones. In many cases this increased fitness at the stem cell level likely comes at a cost – their ability to produce functional mature blood cells is impaired, so explaining the observed age-related loss of function in the blood system.”

What drives this fewer/stronger stem cell pool?

Do improved kidney markers on Rapamycin infer anything about this improved cross talk?

I haven’t read the full study, but we also know, mTOR hyperactivation in old age drives hematopoietic stem cell exhaustion/senescence, and that Rapamycin rejuvenates this pool.

mTOR regulation and therapeutic rejuvenation of aging hematopoietic stem cells

“Together, our data implicate mTOR signaling in HSC aging and show the potential of mTOR inhibitors for restoring hematopoiesis in the elderly.”

#241

Hba1c is within .1 of 5.3 very consistent even from back when I was a bad boy.
Fasting glucose really shows no pattern. As low as 84,85 and the highest was 97 with similar numbers before and after Rapa.

#242

First, I must repeat my paraphrased advice to any younger person taking supplements of any kind: If it ain’t broke you’re not going to fix it. Even if a supplement is doing you a long-term good, you may not be experiencing any immediate benefits.

So, having taken rapamycin for approximately seven months, at ever-increasing doses, I don’t feel like I’ve discovered the “Fountain of Youth” as far as increased energy, etc., but it has had some unexpectedly positive results.
Taking rapamycin has eliminated my “essential” age-related hand tremors.
Eliminated my need to go to my dermatologist for treating chronic actinic keratosis.
Effortlessly maintaining my desired weight without worrying about my diet. (As teenagers are often able to do.)
After six months I am sleeping better than I did at 40.

Here are the latest two of my lipid panels; the first was taken ~ approx 2+ years ago and the latest was taken a few weeks ago. As you can see my lipids have increased rather dramatically after taking rapamycin for ~ 7 months.

Collected: 2/13/2020 09:30

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Collected: 05/26/2022 08:48
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#243

Highlights

  • Only 30% of Atherosclerosis Risk in Communities (ARIC) participants maintained healthy cardiovascular (CV) status at mean age 75 years.

  • Midlife traditional risk factors are associated with CV health in older age.

  • Associations of some traditional risk measures with CV health change with aging.

  • Pulse pressure may be a better marker of CV health with aging than SBP or DBP.

  • Early more-aggressive risk factor modification may promote healthy CV aging.

Full New Paper:

https://www.atherosclerosis-journal.com/article/S0021-9150(22)00220-9/fulltext

#244

Ok so med induced, that makes sense, a different context.

#245

I got a lot of my inspiration from Ivor. Here he goes over the Kraft curves and how they can tell you how well you are doing. I suppose it is expensive to do it this way, but why use something cheap if it doesn’t work?

Those who limited their eating to eight hours a day were 91 per cent more likely to die from cardiovascular disease
#246

Ivor is great…metabolic syndrome = CVD.

#247

Just commenting on the study right now re progression of coronary calcium scores and CAD. I hadn’t seen that study and it was very interesting. As an aside, one of the authors is Roger Blumenthal, a very respected preventive cardiologist at Hopkins.
So, if you have a baseline CAC of zero and then progress by 5 units a year, your risk increases , but it’s still low on an absolute scale.
If your score is non- zero and you progress at 100 or more points/ year, that’s a significant risk. If the progression is 300 or more then that’s a very high risk of both cardiovascular and even total mortality.
This would be a good way to alert your doctor to be more aggressive in your management.
The scan is fairly low radiation risk these days and affordable as well.
Thanks for that study.

#248

Yes that is an amazing reference CAC risk study. Keeping progression < 15%/yr is key.

#249

I think interventions even younger, maybe in the 20’s , would also be beneficial especially in regards to the rapid increase in obesity. Monitoring for visceral fat in the young could be very important.

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#250

Thanks for the paper, that’s interesting (& hopeful) info.

#251

This group out of Brazil demonstrated in a prior study that the ratio of triglycerides to HDL was the most powerful predictor of CAD when over 4.
In this study they show via the gold standard of coronary angiography that the same ratio was also the most powerful indicator of extensive coronary artery disease. These triglyceride rich VLDL particles lead to the very dangerous small density subgroups of LDL.
It would have been interesting if they had looked at ApoB.

#252

@desertshores

Your TG crossing over 150 is clinically hyper TG, but as rivasp12 asks, “do we treat”?

Clearly, Rapamycin appears to have dysregulated your lipids, but you’re otherwise feeling good/“better”?!

Your TG/HDL is 2.5 and remnant cholesterol (TC-LDL-HDL) is 23, both of which would suggest a more atherogenic profile? But you don’t fit the profile of classic metabolic syndrome. I assume normal BP.

Have you had a CAC?

Are you looking deeper into your lipids? Sub particles apoB, sdLDL, etc.

What’s your level of CVD concern? Do you consider taking a statin a medical blockade to your lipids?

#253

The study on the relationship of HbA1c and heart failure doesn’t impress me that much. It looks scary on the graph of relative risk, but the absolute risk between 5.4 and 5.6 is very small per 1000 people. Even at the level of 6.5 the absolute risk seems to be about 1% per the graph and that’s not even considering that the increase in glucose secondary to rapamycin may be entirely benevolent.

#254

at what age should one do a baseline coronary calcium CT ? I have a high lp(a) and ldl (which has been lowered by statin use), but im 24 and i asked my doctor about it and he told me he wouldnt recommend it since I am so young and also my other biomarkers are good along with low CRP.

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#255

Yes, I have been taking Atorvastatin 40mg once daily.
My BP is very good for my age typically < 115/65
My BMI is ~22.3

#256

Well, you’ve got some discordant markers…so what is your “actual” current CVD risk given your lipid dysregulation taking Rapamycin, yet good overall health profile?

I’d do a CAC and look under the hood to see where you are.

#257

This ratio is a well known atherogenic marker, a very good one. That’s way too high TG/HDL near to 4. For anyone with say HDL at 55, even someone with a TG/HDL of 2.72 would be clinically hypertriglyceridemia (TG > 150).

My own personal targets are TG/HDL <1, with remnant cholesterol < 10. My last 4 lab panels hit both metrics.

#258

Your risk metrics are way more generous than mine!

Prediabetes is 5.7%-6.4%, and diabetes 6.5%+.

It is without debate a prediabetic, and especially full on diabetic metabolic profile, is very high risk for CVD. Different risk if rapamycin induced? One major issue is the translation model: most all the data is in mice, and mice don’t die of CVD.

Dr B makes many arguments for benevolent glucose on Rapamycin…yet he includes a conditional caveat:

“No hyperglycemic effects of rapamycin/everolimus have been detected in healthy people. For antiaging purposes, rapamycin/everolimus can be administrated intermittently (e.g., once a week) in combination with intermittent carbohydrate restriction, physical exercise, AND metformin.”

I missed that little add on until now. Why these glucose blunting interventions?

#259

It’s interesting in a recent study that treating pre diabetes reduced the incidence of diabetes but not of cardiovascular events.
Yeah, Blagosklonny is very much into very low carb and high protein diets right now. Not certain that he’s still an advocate of metformin, but one thing is for sure, he’s frequently referred to hyperglycemia secondary to rapamycin as benevolent.