Questions to Matt Kaeberlein

[John_Hemming]

Nail Growth is a good sign of stem cell production. Hence it would reflect a wide range of health issues.

There is also a question about the quality of nails.

Nail Health Chart: Common Problems and Treatment

[Neo]

Do other things like vascular circulation, the environment’s temperature, other hormones, diet, etc affect nail growth at magnitudes that make it touchy to use as barometer of stem cell function - on less changes are done “with all else equal/similar”?

More importantly, do we know if we actually want to have stem cell activity generally revved up… Seems to me that we for a longevity goal perspective may want stem cell activity relatively revved down most of the time, with the capacity to rev up quickly and forcefully occasionally when actually needed?

[John_Hemming]

Although obviously there will be factors that affect stem cell production and quality of nail growth other than aging, we do wish to maintain the renewal systems of the body.

[Neo]

@John_Hemming

to maintain the renewal systems of the body.

Yes, but maintaining the system is not the same as having the system revved up on an ongoing basis.

[John_Hemming]

That’s true, but normally with age stem cell production goes down. My reason for measuring nail growth is an attempt to track that macroscopically. I could probably do with writing some image processing software to process photographs to measure these things, but in the end I am happy with an approximate guide.

[Daph]

Metformin decreases inflammation - an interesting tidbit from Peter Attia’s podcast on inflammation that came out yesterday (#301, AMA #59). I think it did this for me.

Under the category of drugs that decrease inflammation:

Glucose-lowering drugs that are used to treat type 2 diabetes:

• Various diabetes medications, including SGLT2 inhibitors, GLP-1 agonists, DPP-4 inhibitors, thiazides, sulfonylureas, and particularly Metformin, have shown to reduce inflammation.

• These effects might be due to direct anti-inflammatory actions or indirectly through improvements in metabolic health and weight loss.

Metformin and Geroprotection:

• One of the arguments of people who believe that metformin is geroprotective is that this is one of the pathways that metformin targets is directly targeting inflammation.

• This characteristic of Metformin is viewed as extending beyond its primary role in blood sugar regulation, possibly affecting processes like cellular senescence and systemic inflammation.

#301 - AMA #59: Inflammation: its impact on aging and disease risk, and how...

[KarlT]

Dr Attia, though, only prescribes Metformin to patients with diabetes.

[Mike_Potter]

I believe in getting natural vitamin d from the sun should I only get in the sun during the trough period of the rapamycin cycle, not at all, or anytime as long as I don’t burn

[Daph]

I’m pretty sure he’s said several times that he also prescribes it to patients who are metabolically compromised or prediabetic. But that wasn’t my point. I was just sharing some info about why metformin might have helped me, since you had asked. I was sort of surprised to see this finding that metformin is antiinflammatory. I hadn’t realized that or thought of it that way before. I wasn’t sure exactly how it was helping me because it does so many different things. Getting a better understanding now. Just wanted to share since you also seemed curious.

[Daph]

Btw, the doctor who prescribes of my off-label metformin (I am not diabetic) is with a large NYC hospital in their Post-Covid Care Clinic. She wrote the prescription after I told her I’d been taking my husband’s old supply (lower dosages which we saved, but he no longer used) and that it noticeably helped my symptoms. She said it’s a low-risk medicine and she’d be glad to prescribe it, and that I shouldn’t be taking somebody else’s old meds. Eternally grateful for that, though I would have found another source if needed. She was not so kind or accommodating when I told her about my rapamycin experiment at our last visit, in fact I think her may have head spun around a few times. But until conventional medicine has something better to offer, I’ll do what I have to.

[LiveLonger]

Questions for Matt:

Q1 Does it matter if I exercise a few hours before taking rapamycin? Say I exercise at 9-10am and then take rapa at 1pm.

Q2 Is it better to do a dose every 2 weeks or every 1 week? How would one choose?

[Agetron]

I like these questions… I concur… exercise timing and… each week verses 2 week cycle.

Although, he does weekly with periodic breaks.

[Neo]

What are his thoughts on the rebound / overshooting of mTOR after rapa?

Paper and discussion here for those not familiar with the topic:

Rapamycin / MTOR Rebound effect in 3/12 non-GF and non-Keto patients

I’ve done a site wide search and have not been able to find this discussed. I was reviewing “Phase 1 Studies of Sirolimus Alone or in Combination with Pharmacokinetic Modulators in Advance Cancer patients” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4410974/pdf/nihms604208.pdf On page 14, there a figure that shows a rebound effect with Rapamycin. [image] According to the authors "paradoxically, in 6/12 subjects we observed a rebound effect on phospho-p70s6k where phorsphorylated protein levels exceeded baseline at later time points (including 28 days later) Unfortunately, they don’t state explicitly what dose resulted in the rebound, but they do add that “we determined rebound was driven by the concentration of sirolimus” What do you all make of this? 6/12 with rebound; with 3/12 with levels above baseline at 28 days? I realize these are small numbers and it is difficult to draw conclusions. As an aside, did anyone notice that Cmax for the GF baseline 15 mg was greater than the Cmax…

[Barnabas]

This is a nice video to get a sense of Matt’s views on healthspan interventions–in this video he runs through a grab bag of practices and ranks them. Basic from the point of view of many people on this forum, but maybe nice for sharing with longevity-curious friends who aren’t ready to read thousands of posts on here.

The Best Strategies for Living Longer RANKED: Longevity Tier List | 32 - HSM #7

[DeStrider]

It’s interesting that in supplements he ranks:

Vitamin D - A
Creatine - B
Rapamycin - C
NMN - D
Resveratrol - F

Rapamycin at a C? I guess this goes to show how bad a vitamin D deficiency can be!

[Barnabas]

I thought that was a bit surprising too, but it made sense in context. To be clear, he was careful to specify that his (A) grade was assigned to “testing vitamin D level and supplementing to ensure sufficiency” rather than to “taking a vitamin D supplement.” His (C) grade for rapamycin was based on his belief that it is for some but not all people and that it is not without uncertainty (unlike A-grade items like brushing and flossing, sleeping well, and exercising).

[DeStrider]

Yes. I was thoroughly surprised to find I was deficient in vitamin D. Even after taking 5000 IUs a day, I was still deficient (30… Ok. Barely sufficient). I want at least 40, so I am now taking 10000 IUs daily + Magnesium Citrate. Let’s see how my vitamin D levels are this year.

As for Rapamycin, he’s right that it isn’t for everyone. Diabetics need to be EXTREMELY careful and there are some people who just can’t tolerate Rapa at all.

If it were up to me, I’d move Rapamycin up to a B and NMN up to a C. Vitamin D and Resveratrol are where they should be. I’d also put Magnesium at an A and Omega 3 and Taurine at a B.

[Beth]

Wow on you not responding well to that much vit d. Do you happen to know if giving yourself b12 injections would help you absorb it better? I don’t know the answer.

[DeStrider]

I take daily oral B-12. Yeah, I really don’t respond well to vitamin D supplementation. I’m hoping it was due to not enough Magnesium, so I’ve upped my dosages of that as well. I’ll be getting my D levels tested in August, so I should have a better idea as to where I stand.

[Beth]

Whoops, I had a brain fart and confused d for b12…

Never mind… nothing to see here!!!