#14

What confuses me is, despite the erudite commentary, is just how little consensus there is. I wonder whether an almost-definitive list of life extension supplements and drugs is even possible.

I read that some statisticians, after decades of work, have created a model that enables them to compare the quality of baseball players throughout the history of the game, despite all the shifting variables (like the available pool of talent – e.g., there was a time when all ball players were white). Why can’t we do the same with LE supplements?

#15

Oh, and those statisticians chose Barry Bonds as the greatest of all baseball players. Babe Ruth came in fourth.

#16

Also interesting, the more I think about the weirdness in the Mittendorf article, there is bounded evidence that vitamin C is geroprotective in humans. The most robust evidence lies in the area of immunosenescence. Human clinical trials have demonstrated that supplementation with vitamin C can restore certain cellular immune responses in the elderly to levels comparable to those seen in younger adults. Less compelling but interesting, a large cross-sectional analysis of data from NHANES revealed a significant positive correlation between higher dietary vitamin C intake and longer leukocyte telomeres. Vitamin C’s effects on skin aging is also interesting. A cofactor for collagen synthesis, C is essential for skin elasticity and structure and recent studies suggest a deeper mechanism in which vitamin C promotes the proliferation of epidermal cells by facilitating DNA demethylation of genes related to cell growth. Several other avenues of geroprotection are possible but the evidence at this point is contradictory.

#17

The thing to keep in mind is something very basic, the ancient “the dose makes the poison”.

Some molecule might be geroprotective or accelerate aging just with the given dose. That frequently confounds the various studies and reports on these substances. Vitamin C is certainly an example. In addition to dosages you have to ask about the subject - are they deficient, oversaturated, have specific conditions. It might work very differently depending on the cohort and other contexts.

Rapamycin is a good example. If we only knew rapamycin as an immune suppressant in organ rejection it would never come across our radar as a geroprotector.

All these other considerations cause me to be very cautious about claims to geroprotection by this or that substance. Maybe it is or is not because of other factors.

#18

Statins are mitochondria toxin, so i suspect him to be against them. Cholestrol is 80% of the myelin on the brain. When the elderly are put on statins they develop chronic pain n neurodegeneration a few years after

#19

Im surpriced he only takes rapa 8 weeks per year, and twize per week. Josh is very smart so i wonder his reasoning

He had great post regarding the covid vaccine during the pandemic, when most people were still sold on them, he saw right thrue the bs and now 4 years later they are all banned for xx age group due to stroke n myocarditis

#20

Yes vitamin C are one of the most important supps. It also cures cancer at high doses IV as It turns into hydrogen peroxide

#21

I had to comments on his post (and Josh agreed to both) was:

  1. Many of these results are based on only 1 study which makes the results a bit tenuous.

  2. As Matt Kaeberlein has pointed out, you have to distinguish the experiments that have long lived controls to those of short lived controls. The problem with short lived controls is that they typically have some flaw that can be corrected with the supplement, but that the supplement would not cause an increase in lifespan in normal mice. He argues that you should only regard a purported longevity intervention as credible if either: The control group’s median lifespan reaches approximately 900 days (± 50), or the treated group’s final lifespan exceeds 900 days significantly

3 Likes
#22

When you make a statement like that, it would be nice if you included some citations.

3 Likes
#23

This is well known in functional medicin feild, seen tons of docs say this and makes sense as 80% of the myelin in the brain is cholestrol

Just last week a study on alzhimers n cholestrol shown that in alzhimers cholestrol synthesis to the brain is impared = brain disease

The end of statins are here. only a moron would promot statins (peter attia) Cerebrospinal fluid lipoprotein-mediated cholesterol delivery to neurons is impaired in Alzheimer’s disease and involves APOE4 - Journal of Lipid Research

#24

Do you know about the evidence hierarchy, which studies are higher/lower quality evidence and risk of higher/lower bias?

See this thread (or video): Evidence Hierarchy

2 Likes
#25

That is in itself a moronic statement.
Please do a little research before quoting some self-promoting talking head on YouTube.
Bottom line: Statin use is linked to lower risks of all dementia, AD, and VaD.

“This comprehensive systematic review and meta-analysis demonstrates that statin use is associated with a significant reduction in the risk of dementia, including AD and VaD. Our study, encompassing over 7 million patients across 55 observational studies, provides robust evidence supporting the neuroprotective potential of statins.”

"Studies tracking patients who achieved very low LDL-C with PCSK9 inhibitors (often on background statins) found no cognitive impairment, which indirectly argues against a “low-cholesterol causes dementia” effect.

https://alz-journals.onlinelibrary.wiley.com/doi/10.1002/trc2.70039

8 Likes
#26

I recall that Attia did offer his opinion to the effect that statins were nearing the end of their life cycle. In the context of the overall conversation, I think he was saying they are being marginalized by the newer drugs that do an even better job with fewer side effects. I agree, more-or-less, with the caveat that the newer drugs may also turn out to have undesirable side effects once enough people have been taking them for a long enough period of time. On the other hand, we could see statins go OTC, which wouldn’t be a bad idea either.

2 Likes
#27

"Cholesterol is 80% of the myelin on the brain. "

Below is an article on the subject.

Myelin Fat Facts: An Overview of Lipids and Fatty Acid Metabolism - PMC)%20%5B11%5D.

Myelin Fat Facts: An Overview of Lipids and Fatty Acid Metabolism

Yannick Poitelon 1, Ashley M Kopec 1, Sophie Belin 1,*

  • Author information
  • Article notes
  • Copyright and License information

1Department of Neuroscience and Experimental Therapeutics, Albany Medical College, Albany, NY 12208, USA; poitely@amc.edu (Y.P.); kopeca@amc.edu (A.M.K.)

The myelin sheath is characterized by a high proportion of lipids (70%–85%) and consequently a low proportion of proteins (15%–30%). In contrast, most biological membranes have approximatively equivalent ratio of proteins to lipids (50% lipid/50% protein) [8]. The high lipid/protein ratio in myelin contributes to the close packing and tight organization of the myelin sheath through non-covalent interactions between lipids and myelin proteins [9]. In addition, the enrichment in specific classes of lipids is also required for the long-term maintenance of myelin [10].

The three major classes of membrane lipids are cholesterol, phospholipids (e.g., plasmalogen, lecithin, sphingomyelin) and glycolipids (e.g., galactosylceramide). The lipid composition of myelin sheath is distinctive, made of high amounts of cholesterol and enriched in glycolipid, in a ratio of 40%:40%:20% (cholesterol, phospholipid, and glycolipid, respectively) compared to most biological membranes (25%:65%:10%)

#28

So, what?
This discussion is about whether or not statins are harmful to the brain.

2 Likes
#29

Just pointing to the basis of Biohackerofthegods’ statement

This is well known in functional medicin feild, seen tons of docs say this and makes sense as 80% of the myelin in the brain is cholestrol

The source I referenced actually states that the cholesterol percentage is lower.

ratio of 40%:40%:20% (cholesterol, phospholipid, and glycolipid, respectively )

There seems to be evidence for both views - that statins are protective; also that they are detrimental to the brain, according to James M. Ellison, MD, MPH, Geriatric Psychiatrist, Swank Center for Memory Care and Geriatric Consultation, ChristianaCare,

and he cites references in his footnotes.

There is greater evidence for protection than for harm.

Further, a 2017 large prospective study supported the benefits of statins for reducing Alzheimer’s risk. This study deserves our attention because it was a well-controlled, randomized investigation that evaluated dementia and statin use among over 3,000 older adults every two years for an average of 6.1 years. The researchers concluded that statin use was protective against Alzheimer’s in those adults under 65, though it appeared to slightly increase Alzheimer’s risk in adults over 80 years old.

That’s great news, but what about the reports of cognitive problems linked with statin use?

Evidence for Statins Increasing Risk of Dementia

Alarming case reports began to accumulate in the early 2000s. A description of 60 case reports published in 2003 advised taking concerns seriously about statin-related cognitive impairment, though cognitive adverse responses were most likely uncommon. Simvastatin, atorvastatin, and pravastatin were the medications taken by the patients who were described. About half of these patients noticed cognitive problems within two months of starting treatment. The symptoms improved after drug discontinuation in about half of those affected, which is different from what would be expected of a person with Alzheimer’s disease, which is a progressive condition.

The link between cognitive symptoms and statins is supported by a couple of additional lines of evidence. First, some patients with cognitive problems who noted improvement after stopping their statin medication experienced a recurrence when the medication was restarted. Second, a couple of small but well-designed experimental double-blind, placebo-controlled trials associated poorer performance on neuropsychological tests with the use of statins. In a description of statin effects on a couple of affected patients, the authors reminded us that a cognitive effect that looks small on neuropsychological testing can cast a much larger shadow over actual day-to-day functioning.

That is a prospective study of 3,000 patients, versus 60 case studies.

#30

shout out to my statin (simvastatin) on the OP studies…

While I’d prefer to get my hands on fluvastatin one day (I heard it enhances sirt 6, which I already take donotage’s sirt 6 activator), its not available through India and expensive elsewhere I believe…

So, I still take simvastatin once novos (which I take novos core), advocated its the statin they thought which increased lifespan in mice (though I believe they don’t advocate for statin period).

If you do take a statin, we would opt for simvastatin, given this was the only statin that has been shown to also extend lifespan in mice.

So, I’ve taken simvastatin since though I keep hearing about other statins being better

#31

What? I am unaware of any study showing simvastatin alone increased lifespan in mice. It certainly failed in the gold standard ITP trial. And it only worked measurably in combination with a BP med, but not on its own. If there’s a study showing simvastatin alone extended mouse lifespan, I’d like to see it.

Combined statin and angiotensin-converting enzyme (ACE) inhibitor treatment increases the lifespan of long-lived F1 male mice

“The simvastatin and ramipril combination therapy significantly increased the mean and median lifespan by 9 %. In contrast, simvastatin, ramipril, or candesartan monotherapy was ineffective.”

This is similar to the metformin claim. Metformin does not extend lifespan in mice - it failed in the ITP, just as simvastatin failed. It did extend in combination with rapamycin, just as simvastatin did, but only in combination with ramipril.

And many don’t need or want to take a BP med. In which case just taking simvastatin on its own gives us no grounds to project a benefit on the basis of simvastatin alone extending lifespan in mice, as it did not.

In that sense either agent is worse than the metformin rapamycin combo, because at least in that case rapamycin on its own extended lifespan in mice, unlike in the case of simvastatin where neither it alone, nor ramipril alone extended lifespan in mice according to the study I posted above.

2 Likes
#32

What do you mean when you say “they (Covid vaccines?) are banned for xx age group”? Banned where, and for what age group?

#33

I honestly don’t care if rapamycin extends my lifespan or not. It’s about the quality of my life, and rapamycin has so far been the only thing that reduces my arthritis and cervical stenosis pain.

I’ve tested it repeatedly, and without rapamycin, I’m in a lot more chronic pain than if I take it regularly. It takes about a month for the effects to start wearing off, but six weeks I am back in pain, and it only takes about two weekly doses for the pain to start retreating. I’ve tried just about everything else. Low Dose Naltrexone helps, so do the anti-inflammatories and NSAIDs, but I can’t take ibuprofen anymore due to nephrotoxicity. Nothing touches rapamycin though. It’s been miraculous.

If you told me that it would take a year off my life, I’d still use it. I just recently had a reactivation of Epstein-Barr virus, and I think rapamycin may have possibly played a role in that (but I was also moving internationally, so yeah, stressful), but as soon as I was over the worst of it, I went right back on.

1 Like