If longevity was a programmed feature, statins wouldn’t decrease all cause mortality in humans and rapamycin wouldn’t increase median and maximum lifespan by so much in the ITP mice trials. Some people/mice get lucky but luck is far from being the only component in longevity.
1 Like
That “luck” you are talking about could be a pre-programmed trait. We know so little.
Well we have ranged far afield from Dr. Longo but it is an interesting turn. I think that you have made some good points and missed a few.
- complete agreement in understanding that cholesterol is super important to life
- As far as having a cholesterol making mechanism if we don’t consume enough, yes! BUT this is one of many places where the public has been misled. As I understand it MOST of our cholesterol production is endogenous. The absorbed portion is much smaller and so it’s actually hard for most systems (depending on genetics) to change the levels via diet.
- I recently heard Peter Attia discuss treatment of Familial Hypercholesterolemia (high particle counts) with a cardiologist in Holland where they have an unusually high genetic tendency towards this disease. Enlightening discussion. He treats people, even children who have lost parents at an young age due to this. Their particle counts are extreme and CVD takes it’s toll early on this population. Now, perhaps they also all have poor endothelial function, but this is a stretch for people in their 30s. More likely it’s that the trauma of constant blasting of many more particles can overwhelm even healthier endothelial linings. Treating with statins (and they are developing better approaches) really, very clearly saves lives that would be ended in middle age or younger.
- This Dutch doc hypothesizes that, like other genetics that are prevalent but seem counter to health, high quantities of particles (more cholesterol) were a survival advantage during periods of extreme scarcity. People could live on less and survive to reproduce. But as food supplies increased, it became a liability to long life instead of an asset to a just-long-enough life. Point being, just because we have evolved a prevalence of a certain genetic …what is it? phenotype?.. that does not mean that genetic profile is best for modern circumstances and longevity.
- Agreed that fear of cholesterol is manufactured and misplaced. What we are learning is that it’s not really the cholesterol per se, it’s the particles, the lipids themselves that create a constant ongoing impact load on our CV system. Medicine measures the cholesterol because yes, it was the easiest one to measure and it’s usually the particle’s passenger. Like measuring people on the highway to determine how much wear the highway might have. It’s more accurate to measure the number and size of the vehicles not the number of people, but that’s the evolving science.
- Agreed in part about the process and the endothelial cells. But it’s not either/or, it’s a dynamic mix of both, it seems. Continuing the analogy of traffic wear and tear we can recognize that a poorly paved road will suffer more with the same traffic than a well built one. Endothelial integrity is thus a crucial component in the dynamic, but not exclusive. A super strong road will handle more traffic over the years with less damage. On the other hand, the wearing effect of higher traffic is a significant factor in the mix. Even a weak road can last with no traffic. High particle counts do offer some indication of how worn things might be but a strong vascular system can likely take much more than a weakened one. And conversely, as those treating FH know, a really high traffic level will induce high wear on even a high quality pavement.
In sum, for myself, I am trying to reduce my chances of developing CVD to a threatening level. It’s there, it’s a lifelong wear factor. But I want to knock down the likelihood that this will shorten my life or health span. So, to maintain good endothelial function, I want to reduce inflammation. I have a problem here that is not easy to address, but I wish to.
AND ALSO, the sooner I knock down the numbers of particles, the less cumulative effect they can have on whatever quality of endothelial cells I have. Since it’s a long-term cumulative effect, the sooner I can reduce this, the less long -term damage to the vessel walls.
As important as cholesterol is, with such an abundant diet and nutrition as we have in modern times, I’m not concerned about suffering inadequate cholesterol levels due to treatment. This seems to be a rare issue.
- The studies cited to negate the impact cholesterol carrying particles have been considered elsewhere here already so I won’t repeat.
Anyway, thanks for bringing this up and I really do encourage listening to that discussion. #255 ‒ Latest therapeutics in CVD, APOE’s role in Alzheimer’s disease and CVD, familial hypercholesterolemia, and more | John Kastelein, M.D., Ph.D. - Peter Attia (peterattiamd.com) I ignored this episode for some time as FH is not a concern, but I learned how, as an extreme, it illuminates the degrading processes for all of us.
4 Likes
Watch out for that . Do a lot of research on Post-finasteride syndrome. Not worth it is my takeaway.
2 Likes
Thank you for the reasoned and imformative reply!
Post Finasteride Syndrome has no actual clinical research indicating it exists at all. Even observational trials have mixed results with some men on finasteride actually having lower rates of persistent ED than men not on finasteride.
1 Like
It took be about 6 months to feel normal and have normal function after I quit. Happy for anyone who can take it, it works wonders for many people.
2 Likes
Although anecdotal, good information on your experience. I don’t understand why someone would take Finasteride with better options available.
3 Likes
Hi Ellie, You’re running a farm in rural Oregon by yourself at 80 - you’re doing pretty well!
I tend to think that while evolution may not be “profligate of biological energy reserves”, I don’t think that evolution cares much about the body after procreation. You’re probably aware of the disposable soma theory:
But lets not digress too much on this thread (start a new thread if a post here triggers a new conversation)…
And - if you want to review a long, and in-depth discussion of cholesterol I recommend you check out this thread: Rapamycin and risk of cardiovascular disease
3 Likes
Statins can do many things for any number of reasons that have nothing to do with cholesterol.
Let’s say you do everything right from birth, all the right nutrients at the right time including exercise, sunlight etc… you don’t live forever right? Do you expect the next guy who does everything right from birth to live the exact same number of years? He has a different code, he’s a different machine. Now mix in the fact that it’s impossible to do everything right since we don’t even know what it is.
Things are so much more complicated than just hacking cholesterol.
I’m a farmer too. Tillage does dozens of things good and bad. People want to just look at the good. Or some just look at the bad. Very hard to weigh. Bring in a new technology that fixes all the bad and we might have something.
I really like the Cavidex cyclodextrin solution. They only pick up small dense LDL and turn foam cells back into macrophages. It doesn’t reduce all the cholesterol, only the bad stuff. Brilliant. Good things are coming. Soon we will stop arguing about this.
2 Likes
Bring in a new technology that fixes all the bad and we might have something.
Perfect is the enemy of good. If you wait for the perfect anti-aging drug with zero side effects (not even imagined ones that many people on the internet get) you’ll be long dead before it comes out (if it ever comes out).
The net benefit is all that really matters in the end.
1 Like
There is a Peter Attia Drive great podcast about rapamycin with Matt Kaeberlein where they discuss the protein conundrum. Peter acknowledges that animal protein rich in leucine and isoleucine is a big time activator of M-tor pathway. He struggles with that fact but feels like the low protein can lead to sarcopenia.
However the observational studies of Centenarians in the blue zones revealed that they solved this conundrum by natural selection.
Like most of things life, this is a Goldilock situation. In order to reduce senescence and inflammation one must minimize stimulating M-tor pathway, but not necessarily completely inhibit it. Centenarians in blue zones eat 95% plant based diet, but do eat animal protein. They eat low calorie, high plant protein foods with small amounts of animal protein on average per day. I am guessing (very rough guess) 20% of their total protein intake. Plant protein unlike animal protein is low in BCAA’s and doesn’t stimulate M-tor in the same fashion.
Personally I strive for about 1 gram/pound of protein per day which 70-80% comes from plant sources (whole grain, legumes, nuts and seeds) and I restrict animal protein to about 4 hour window a day - more or less. Some days I will eat more animal protein if wife makes something special.
I exercise about 10-15 hours a week, consume 4-5 tsp of Matcha green tea and 1800 mg of curcumin a day - all of which are selective or complete m-tor pathway inhibitors.
I disagree with a comment above who said that plant protein is not tasty. My tempeh sauteed in olive oil and spices, served on Ezekiel bread with Watercress, mayo, mustard and tomato is way more delicious than boring deli meat.
6 Likes
In one of blue zone (southern Italy), I know for a fact that they eat a lot of animal protein (included here fish). Having one two meals per day either meat or fish of some sort (most likely over 50% of calories coming from animal protein) but I am also aware that people in other regions blue zones consume more of a plant-based diet. So, the fact that these people live longer may not be linked directly with just what they eat (mainly plant or animal diets/proteins). Many other factors at play and in some cases including even weather (this case dry & sunny) plus they stay active/work well into their 90’s or later. Limiting calorie intake to a normal level does help in being healthy IMO (plant or animal may or may not be as important, even though animal protein sits better with me)
1 Like
Your outlier does not disprove my point in any way. Maybe people in that particular zone are especially active and offset the deleterious m-tor activation via exercise more than in other zones. The zones most dense in Centenarians are in fact 95% plant based. Focusing on plant protein along with activity may ward off sarcopenia while not over-stimulating the M-tor pathway. Moreover plant protein comes with a lot of other benefits such as extra fiber and phytonutrients. Just google Genistein, show me a study where a beef steak has anti-tumor activity. Not I wouldn’t occasionally eat one, but I am better off eating Minestrone soup on regular basis, just like people in Sardinia do on daily basis.
2 Likes
I don’t mean to go back and forth on this subject, but I think there is still much we don’t know exactly why some zones or people if you will live much longer than the rest. As for you having the minestrone soup and me having the steak, I will take you on that offer 
However I’ll do it reluctantly since i like both. How about I’ll have my minestrone and the steak and you stick with your minestrone hahaa. you better wish you never crossed a carnivore if you are plant-based guy though :). But I do concur strength does not always translate into longevity.
2 Likes
I am cat 1 mountain bike racer in a SingleSpeed category. I am 49 and podium on most races, beating out much younger carnivores. I am 510, 150 lbs pounds and can squat 3 sets of 10 reps of 380 lbs. I don’t go for size in the gym to keep my weight low but rather just strength. So I am not sure why you would imply that one cannot get strong on adequate plant protein mixed with some animal protein daily? Protein is the only macro I really keep a track of. Obviously I am case study but there is no preponderance of evidence in clinical studies that favors one type of protein over the other for muscle building, as long as plant protein is carefully cultivated.
2 Likes
I hear you but when you get this Doc saying best protein is red meat, what do I know?
RED MEAT: The Single BEST Food for Healing and Repair - YouTube
I’m tempted to believe though that a mainly meat diet may not be as good as a balanced mainly plant diet for longevity (I only count anything over 105 years old as living more than normal since I know a few people who are in their late 90’s and a few that passed at 98-100 without doing anything in particular to live that long. One of them was a regular drinker, 3-5 drinks of brandy daily, and was also fat but ate only one meal a day meat+rice and beans etc …) . However, I do think fish protein is extremely healthy and good for longevity.
That sandwich does sounds very tasty!
2 Likes