The four best longevity interventions?

#163

Your chart gives one star to CR and 3 stars for rapa if given late in life. This is incorrect. CR certainly doesn’t work as well at increasing absolute lifespan when started late than when started earlier, but the magnitude of the remaining lifespan increase is similar when started in old vs. young, and the absolute or remaining increase is greater for CR than it is for rapa when started at the same age. Compare:
40% CR initiated at 19 months of age
“CR extended mean lifespan from 30.7 ± 0.7 (SE) to 35.4 ± 0.8 months (P = .000017) and extended maximum lifespan from 37.6 to 43.6 months (P = 0.000056)”

Rapamycin begun at 19-20 months of age (ITP)
“Expressed as mean lifespan, the effect sizes were 9% for males and 13% for females in the pooled data set.”
Masimum lifespan
Females
Rapamycin 1,245 versus controls 1,094
Males
Rapamycin 1,179 versus controls 1,078

Note also that the mice in the CR study were male, and that the extension of lifespan was greater than for either male or female mice given rapamycin.

(Yes, two different studies, different mouse hybrids, etc. Still).

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#164

Thanks for the very informative post! I really appreciate it. One reason why I added one star on it was because of Matt Kaeberlein summary in the topic where he says that it works in around 1/3 of the cases. Is that aligned with your view also?

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#165

No: it works in almost all mouse strains, and the ones in which it doesn’t work (or works minimally) are serious freaks. The idea that 1/3 of mouse strains either don’t respond to CR or have their lifespans shortened is based on a very flawed genetic study that has somehow fooled a lot of very intelligent people in the geroscience community.

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#166

Really great information! Does there exist any study pointing this out or something else because it seems as you say a big misconception if this is the case. I believe what you are saying but do you have a source that it does not work only in 1/3.of the cases?

Should I change the stars to three instead of one?

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#167

I use to be a big fan of Dave and Bulletproof; I appreciate his trail-blazing the industry in biohacking our health. But now that we have so much information available via the net, he has become an obsolete source. He, like other older influencers, is trying to reinvent themselves, hanging on to selling or endorsing products that have little to no research behind them, inevitably making them, a "has-been’ in the field of aging.

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#168

It’s very sad development when it becomes to sellish everything and that makes it also hard for the users to know what is sales information and not.

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#169

Its a difficult thing as to how to assess the arguments. If someone has a financial advantage in arguing a particular viewpoint then one has to have some scepticism as to their arguments. However, if someone is not really affected by whether or not people agree with their arguments then they may be so relaxed about the situation that they do not persuade anyone.

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#170

AKG has a very small effect on lifespan (though a larger effect on frailty) in female mice, and a negligible effect in males.

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#171

Does it? Even if what they say is true, the fact that a “NASA scientist” developed and patented a device doesn’t mean NASA ever used or endorsed it. Remember, Durk Pearson used to lay claim to being a “NASA scientist,” and I think you can be pretty sure astronauts were not swallowing his fistfulls of antioxidants or turning themselves orange-tan with canthaxanthin.

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#172

That’s arginine AKG, not calcium AKG, and as you say, the fact that AAKG is useless as an ergogenic doesn’t say anything about its value as an anti-aging, anti-frailty supplement.

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#173

Old thread. But wanna chime in and say that electromagnetic whatever always seemed like total hooey to me too but I’ve recently come to change my mind. See:

Also a ton of studies referenced here:

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#174

Well, I already had a grounding rod, wire and drill bit. Only needed to order:

I wonder if anybody makes grounding shoes that have spikes going into the earth for traction and then attached to a sock with the silver fibers. That would be good for hiking in the wild.

I agree it sounds like hooey, maybe I’m getting desperate.

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#175

I bought just the pillow case as my head is always touching the pillow and electrons flow if you give them a path — in theory. It’s going to be delivered soon though I’m on vacation in Europe and won’t get to try till September.

This video was pretty interesting — I recommend watching with 1.5-1.75x speed because life is short and they talk slow.

#176

Maybe talking slow is a side effect of being too grounded…

I’ve heard hippies talk about this for quite some time now, either they’re all just very grounded, or there’s a confounder :man_shrugging:t2:

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#177

Started on 1.25mg of selegeline today (age=44) :blush:. Plan on using it for life. Split into four, but not looking equal size, but thought “perfection is the enemy of the good”. Will do the four days a week protocol to avoid seratonin sickness (on a SRI)

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#178

O it is an interview late in. His life.

#179

From what I have read if you want to increase systemic levels of arginine the best thing to intake isn’t arginine itself but L-citrulline.

The study below explains it, but to make it short here when arginine is ingested a fair bit of it is converted to urea and orthinine before the arginine itself gets into the body, whereas citrulline bypasses this and goes on to synthesize arginine within the body in multiple locations.

I’ve started taking citrulline, but I’m also looking to start taking either L-arginine or L-arginine alpha-ketoglutarate.

image

l-Citrulline Supplementation: Impact on Cardiometabolic Health

https://www.mdpi.com/2072-6643/10/7/921

This should improve nitric oxide synthesis which will counteract the worsening of biological age related increases in asymmetric dimethylarginine (ADMA) and arginase which destroy arginine leading to a downregulation of nitric oxide synthesis which has downstream negative impacts on many systems of the body including but not limited to the L-tryptophan to L-kynurenine ratio which has its own negative implications when it gets out of whack.

I found this information when doing more research on indolepropionamide: 268% Median Lifespan Increase with Indolepropionamide aka Indole-3-propionamide or IPAM – What this is, and why more studies NEED to be funded!

Indolepropionamide and other gut derived endogenous indoles exert powerful antioxidant effects in the body. These indoles being downstream of L-tryptophan metabolism are reduced when the L-tryptophan to L-kynurenine ratio skews towards L-kynurenine.

This tells me that if we can find ways of reliably tracking ADMA/arginase, the L-tryptophan:L-kynurenine ratio and overall levels of systemic antioxidant indoles we would have very useful biomarkers for an overall biological aging clock.

A strategy of improving NOS and gut health is likely a necessary piece of the puzzle of longevity.

Combining this with low dose tadalafil could also extend how long NO is circulating. Possibly adding exogenous indolepropionamide on top of this could be a big winner as well.

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268% Median Lifespan Increase with Indolepropionamide aka Indole-3-propionamide or IPAM – What this is, and why more studies NEED to be funded!
Humans Age Faster at 2 Specific Times in Their Life, Study Finds
#180

What is your opinion now after using the grounded pillowcase for over a year’s time?

#181

I think citrulline is beneficial. I take about 1 gram in the morning and 1 gram i the evening. To get the effects I want, I am more and more leaning into supplementing it amino acids: taurine, Glycine, acetyl-cysteine. And I try to avoid taking too many polyphenols at the same time/day.

" Evidence continues to emerge on the positive impact of chronic L-CIT on vascular and skeletal muscle function in older adults. L-CIT may improveexercisecapacity byupregulating muscular Perfusion and subsequent oxygen utilization. Evidence suggests that increased L-ARG and NO availability in skeletal muscle may be a crucial factor in promoting muscle function via PGC-1α stimulation of mitochondrial respiratory capacity. In addition, the action of L-CIT on muscle function also is related to its ability to promote muscle protein synthesis"

Revue-Figueroa-Moinard-2020.pdf

Frontiers | L-Citrulline Supplementation Increases Plasma Nitric Oxide Levels and Reduces Arginase Activity in Patients With Type 2 Diabetes

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#182

There’s definitely something to it in the sense of mechanistically conducting electricity. Sometimes I feel an unmistakable subtle zap. But I can’t say I’ve used it very regularly because when I wash the pillow case I don’t put it back on until it makes its way to the clean laundry and the one it got replaced by is due for a change. So I use it intermittently and if I can call the times I don’t use it my cross over phase, I can’t say I notice anything positive or negative so I wouldn’t bother. Perhaps it’s having physiological effects that I just can’t detect but I doubt they’re large.

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